FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Armant, M Waters, C D'Alessandro, D Leri, A Kajstura, J Anversa, P Ritz, J Silberstein, L AF Armant, M. Waters, C. D'Alessandro, D. Leri, A. Kajstura, J. Anversa, P. Ritz, J. Silberstein, L. TI Development of cGMP-Compliant Methods for Isolation and Expansion of Autologous Cardiac Stem Cells for the Treatment of Advanced Ischemic Heart Disease SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 22-25, 2011 CL San Diego, CA SP AABB C1 [Armant, M.; Waters, C.; Ritz, J.; Silberstein, L.] Ctr Human Cell Therapy, Immune Dis Inst, Boston, MA USA. [Leri, A.; Kajstura, J.; Anversa, P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Alessandro, D.] Montefiore Med Ctr, Bronx, NY 10467 USA. EM armant@idi.harvard.edu NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2011 VL 51 SU 3 SI SI BP 222A EP 223A PG 2 WC Hematology SC Hematology GA 822YC UT WOS:000295085500572 ER PT J AU Shang, SB Harton, M Tamayo, MH Shanley, C Palanisamy, GS Caraway, M Chan, ED Basaraba, RJ Orme, IM Ordway, DJ AF Shang, Shaobin Harton, Marisa Tamayo, Marcela Henao Shanley, Crystal Palanisamy, Gopinath S. Caraway, Megan Chan, Edward D. Basaraba, Randall J. Orme, Ian M. Ordway, Diane J. TI Increased Foxp3 expression in guinea pigs infected with W-Beijing strains of M-tuberculosis SO TUBERCULOSIS LA English DT Article DE Mycobacterium tuberculosis; Guinea pig; Foxp3+regulatory T cells; Clinical isolates; W-Beijing strains ID DRUG-RESISTANT TUBERCULOSIS; CELLULAR IMMUNE-RESPONSE; MODEL; PROTECTION; EMERGENCE; VIRULENCE; VACCINES; DISEASE; CELLS AB There is increasing evidence that clinical isolates of Mycobacterium tuberculosis that belong to the W-Beijing genotype of newly emerging strains are often of very high virulence when tested in small animal models, including the mouse and guinea pig. In this report we provide further evidence to support this contention, and show that two W-Beijing strains are of very high virulence when introduced by low dose aerosol into outbred guinea pigs. In addition to severe lung pathology, each of these infections was associated with large influxes of activated CD4 and CD8 T cells into the lungs. Large influxes of macrophages were also observed, but the fraction of these showing evidence of activation by Class-II expression was relatively low. A progressive increase in neutrophils was also seen, with highest levels accumulating in the lungs of the W-Beijing infected animals. In the case of these two infections mRNA levels for TH1 cytokines was elevated early, but these then declined, and were replaced by increasing levels of message encoding for Foxp3, IL-10, and TGF beta. These observations support the hypothesis that W-Beijing strains are potent inducers of regulatory T cells, and that this event may enhance survival and transmission of these bacilli. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Shang, Shaobin; Harton, Marisa; Tamayo, Marcela Henao; Shanley, Crystal; Palanisamy, Gopinath S.; Caraway, Megan; Basaraba, Randall J.; Orme, Ian M.; Ordway, Diane J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. [Chan, Edward D.] Univ Colorado, Sch Med, Denver Vet Affairs Med Ctr, Boulder, CO 80309 USA. [Chan, Edward D.] Univ Colorado, Sch Med, Dept Med, Boulder, CO 80309 USA. [Chan, Edward D.] Univ Colorado, Sch Med, Div Pulm Sci & Crit Care Med, Boulder, CO 80309 USA. RP Ordway, DJ (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USA. EM D.Ordway-Rodriguez@colostate.edu RI Shang, Shaobin/K-5669-2015 OI Shang, Shaobin/0000-0003-4407-1911 FU NIH [AI083856-02, AI070456, 1DP2OD006450]; ARRA funds; College of Veterinary Medicine and Biomedical Sciences, Colorado State University FX This work was supported by NIH grant's AI083856-02, AI070456 and NIH Innovation award 1DP2OD006450, and ARRA funds. Further support was provided by the College of Veterinary Medicine and Biomedical Sciences, Colorado State University. NR 30 TC 28 Z9 28 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD SEP PY 2011 VL 91 IS 5 SI SI BP 378 EP 385 DI 10.1016/j.tube.2011.06.001 PG 8 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 827XE UT WOS:000295462300005 PM 21737349 ER PT J AU Cashman, EC MacMahon, PJ Shelly, MJ Kavanagh, EC AF Cashman, Emma C. MacMahon, Peter J. Shelly, Martin J. Kavanagh, Eoin C. TI Role of Positron Emission Tomography- Computed Tomography in Head and Neck Cancer SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE computed tomography; head and neck cancer; positron emission tomography ID SQUAMOUS-CELL-CARCINOMA; LYMPH-NODE METASTASES; UNKNOWN PRIMARY TUMOR; STAGE-IV HEAD; DISTANT METASTASES; NASOPHARYNGEAL CARCINOMA; F-18-FDG PET/CT; FDG-PET; RADIATION TREATMENT; THYROID-CARCINOMA AB Head and neck squamous cell carcinoma (HNC) is the sixth most common cancer worldwide. In the United States, it accounts for approximately 2% of all cancers and 2% of cancer deaths. The introduction of integrated positron emission tomography and computed tomography (PET/CT) has revolutionized imaging by permitting improved and more accurate anatomic localization of functional abnormalities in the complex territory of the head and neck region, and PET/CT has become a standard clinical imaging modality in patients with HNC. The main indications for PET/CT in HNC are in pretherapy staging, detection of unknown primaries, and monitoring of therapy response or disease surveillance. Although PET/CT is a promising tool in diagnosis and surveillance of HNC, there is lack of consensus as to its use, accuracy, and implications for patient management. The existing literature on the role of PET/CT in the management of HNC is reviewed, and a summary of the current debate is provided. Second primary cancers are the main cause of death among HNC patients with early disease, and the presence of distant metastases greatly impairs the survival of patients with advanced HNC. Therefore, early detection of second primary and metastatic tumors is imperative for optimizing survival outcome. However, given the lack of randomized, prospective trials addressing the role of PET/CT after chemoradiotherapy, the ideal function of PET/CT in disease surveillance has yet to be defined. C1 [Cashman, Emma C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [MacMahon, Peter J.; Shelly, Martin J.; Kavanagh, Eoin C.] Mater Misericordiae Univ Hosp, Dept Radiol, Dublin, Ireland. RP Cashman, EC (reprint author), 92 Beacon St, Boston, MA 02108 USA. NR 76 TC 8 Z9 8 U1 0 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 SEP PY 2011 VL 120 IS 9 BP 593 EP 602 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 824KB UT WOS:000295199700007 PM 22032073 ER PT J AU Zeitels, SM Burns, JA Wain, JC Wright, CD Rosenberg, AE AF Zeitels, Steven M. Burns, James A. Wain, John C. Wright, Cameron D. Rosenberg, Andrew E. TI Function Preservation Surgery in Patients With Chondrosarcoma of the Cricoid Cartilage SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY APR 27-28, 2011 CL Chicago, IL SP Amer Broncho Esophagol Assoc DE chondrosarcoma; cricoid cartilage; laryngeal cancer; larynx; partial laryngectomy; subglottic reconstruction; subglottic tumor ID LARYNX; TUMORS AB Chondrosarcoma is a rare laryngeal neoplasm that is most commonly encountered in the cricoid cartilage and is optimally treated by surgical excision. It is typically a slow-growing malignancy with well-defined margins and a minimal risk of metastasis; however, radiographic imaging studies often appear ominous if the clinician correlates these findings to the biological behavior of epithelial cancer. Furthermore, the fact that the neoplasm's epicenter is usually under the cricoarytenoid joint can lead to airway and voice deficits before and after operation. Although many surgeons opt for function-sparing resection approaches, it is commonplace for some surgeons to injudiciously perform total laryngectomy as the initial treatment because of the rarity, large size, location, and appearance of these tumors on imaging studies. A retrospective review was done on 10 cases of cricoid chondrosarcoma to gain insight into the treatment strategies designed to preserve laryngeal function while minimizing the risk of local recurrence. We performed surgical resection in 8 of the 10 patients; 2 underwent endoscopic removal and 6 underwent transcervical partial laryngectomy. All are free of disease with good voice and swallowing function. One patient developed a limited recurrence and required a second transcervical partial laryngectomy. Function-sparing surgical treatment of chondrosarcomas of the cricoid cartilage can usually be achieved. Surgeons should carefully modify the core principles of epithelial cancer surgery techniques, adjusting to the different biological behavior of laryngeal chondrosarcomas. C1 [Zeitels, Steven M.; Burns, James A.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Zeitels, Steven M.; Burns, James A.; Wain, John C.; Wright, Cameron D.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. [Rosenberg, Andrew E.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. [Wain, John C.; Wright, Cameron D.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Rosenberg, Andrew E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq, Boston, MA 02114 USA. NR 11 TC 10 Z9 10 U1 1 U2 3 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD SEP PY 2011 VL 120 IS 9 BP 603 EP 607 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 824KB UT WOS:000295199700008 PM 22032074 ER PT J AU Reeves, MJ Grau-Sepulveda, MV Fonarow, GC Olson, DM Smith, EE Schwamm, LH AF Reeves, Mathew J. Grau-Sepulveda, Maria V. Fonarow, Gregg C. Olson, DaiWai M. Smith, Eric E. Schwamm, Lee H. TI Are Quality Improvements in the Get With The Guidelines-Stroke Program Related to Better Care or Better Data Documentation? SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE registries; quality of health care; stroke; therapy; data quality; quality improvement ID TRANSIENT ISCHEMIC ATTACK; PERFORMANCE-MEASURES; ATRIAL-FIBRILLATION; AMERICAN-COLLEGE; HEART-FAILURE; OUTCOMES; TRENDS; RELIABILITY; CARDIOLOGY; REGISTRY AB Background-Increased compliance with performance measures could reflect better care or better data documentation. We examined trends in the documentation of eligibility criteria, treatment contraindications, and missing data in the Get With The Guidelines-Stroke program to quantify their contribution to increased performance measure compliance. Methods and Results-Data on 569 883 ischemic stroke admissions to 1028 GWTG-Stroke hospitals between April 2003 and September 2009 were obtained. Seven measures were examined: intravenous recombinant tissue plasminogen activator therapy, early antithrombotics, deep vein thrombosis prophylaxis, anticoagulants for atrial fibrillation/flutter, discharge antithrombotics, lipid therapy, and smoking cessation. Within each target population, the proportion of subjects treated, not treated, not treated because of contraindications, or with missing data were generated by calendar year. There were minimal changes in the size of the target populations for 6 of the measures; however, the size of the deep vein thrombosis prophylaxis population was reduced approximate to 5% in 2008 because of a format change to the data collection form. All measures showed significant increases in the proportion of eligible subjects treated across the study period. These increases occurred without major shifts in contraindications or missing data, with the exception of anticoagulation for atrial fibrillation/flutter where the increase occurred in conjunction with a decline in contraindications. Similar findings were seen when the data were examined by the duration of hospital participation in the program. Conclusions-These findings suggest that the majority of performance improvement in the Get With The GuidelinesStroke program represent an increase in the number of patients with stroke treated and not changes to the underlying target populations or documentation of contraindications or missing data. (Circ Cardiovasc Qual Outcomes. 2011;4:503-511.) C1 [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Grau-Sepulveda, Maria V.; Olson, DaiWai M.] Duke Clin Res Inst, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Smith, Eric E.] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Reeves, MJ (reprint author), Michigan State Univ, Dept Epidemiol, B 601 W Fee Hall, E Lansing, MI 48824 USA. EM reevesm@msu.edu RI Smith, Eric/C-5443-2012 OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; American Heart Association Pharmaceutical Roundtable; Boehringer-Ingelheim; Merck FX The GWTG-Stroke program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke program is currently supported in part by a charitable contribution from the Bristol-Myers Squib/Sanofi Pharmaceutical Partnership and the American Heart Association Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past through support from Boehringer-Ingelheim and Merck. NR 18 TC 20 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2011 VL 4 IS 5 BP 503 EP U45 DI 10.1161/CIRCOUTCOMES.111.961755 PG 20 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 822FH UT WOS:000295028800007 PM 21828344 ER PT J AU Elderon, L Smolderen, KG Na, B Whooley, MA AF Elderon, Larkin Smolderen, Kim G. Na, Beeya Whooley, Mary A. TI Accuracy and Prognostic Value of American Heart Association-Recommended Depression Screening in Patients With Coronary Heart Disease Data From the Heart and Soul Study SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cardiovascular diseases; diagnosis; prognosis; psychiatric comorbidity; risk factors ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED-CONTROLLED-TRIAL; CASE-FINDING INSTRUMENTS; CARDIOVASCULAR EVENTS; ARTERY-DISEASE; COLLABORATIVE CARE; VALIDITY; EPIDEMIOLOGY; PREVALENCE; PREVENTION AB Background-In 2008, the American Heart Association (AHA) recommended a 2-step screening method, consisting of the 2-item Patient Health Questionnaire (PHQ-2) followed by the 9-item Patient Health Questionnaire (PHQ-9), for identifying depression in cardiovascular patients. The accuracy and prognostic value of this screening method have not been evaluated. Methods and Results-We administered the 2-step AHA-recommended screening algorithm to 1024 patients with stable coronary heart disease and calculated sensitivity and specificity against a gold standard interview for major depressive disorder. Subsequent cardiovascular events (myocardial infarction, stroke, transient ischemic attack, heart failure, or death) were determined during a mean of 6.27 +/- 2.11 years of follow-up. The AHA-recommended screening method had high specificity (0.91; 95% confidence interval, 0.89 to 0.93) but low sensitivity (0.52; 95% confidence interval, 0.4 6 to 0.59) for a diagnosis of major depressive disorder. Participants who screened positive on the AHA depression protocol had a 55% greater risk of events than those who screened negative (age-adjusted hazard ratio, 1.55; 95% confidence interval, 1.21 to 1.97; P=0.0005). After adjustment for age, sex, body mass index, history of myocardial infarction, hypertension, diabetes, heart failure, and high-density lipoprotein levels, screening positive remained associated with a 41% greater rate of cardiovascular events (hazard ratio, 1.41; 95% confidence interval, 1.10 to 1.81; P=0.008). Conclusions-Among outpatients with stable coronary heart disease, the AHA-recommended depression screening protocol is highly specific for depression and identifies patients at risk for adverse cardiovascular outcomes. (Circ Cardiovasc Qual Outcomes. 2011;4:533-540.) C1 [Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Elderon, Larkin] Univ Calif San Francisco, Sch Med, St Lukes Mid Amer Heart & Vasc Inst, Kansas City, MO USA. [Smolderen, Kim G.] Tilburg Univ, Dept Med Psychol & Neuropsychol, Tilburg, Netherlands. [Na, Beeya; Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Whooley, MA (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement St 111A1, San Francisco, CA 94121 USA. EM mary.whooley@ucsf.edu RI Smolderen, Kim/B-8078-2015; OI Elderon, Larkin/0000-0002-9620-7756 FU UCSF School of Medicine; University of California, San Francisco; Department of Veterans Affairs, the National Heart, Lung, and Blood Institute [R01 HL079235]; American Federation for Aging Research; Robert Wood Johnson Foundation; Ischemia Research and Education Foundation; American Heart Association Pharmaceutical Roundtable; David and Stevie Spina [0875149N] FX Larkin Elderon was supported by the UCSF School of Medicine Dean's Summer Research Fellowship and by a Student Research Training Program grant from the University of California, San Francisco. The Heart and Soul Study was supported by the Department of Veterans Affairs, the National Heart, Lung, and Blood Institute (R01 HL079235); the American Federation for Aging Research; the Robert Wood Johnson Foundation; and the Ischemia Research and Education Foundation. Dr Smolderen was supported by the Outcomes Research post-doctoral fellowship awarded by the American Heart Association Pharmaceutical Roundtable and David and Stevie Spina [grant number AHA No. 0875149N]. The funding organizations had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. NR 33 TC 32 Z9 36 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD SEP PY 2011 VL 4 IS 5 BP 533 EP 540 DI 10.1161/CIRCOUTCOMES.110.960302 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 822FH UT WOS:000295028800010 PM 21862720 ER PT J AU Kahraman, S Dirice, E Hapil, FZ Ertosun, MG Ozturk, S Griffith, TS Sanlioglu, S Sanlioglu, AD AF Kahraman, Sevim Dirice, Ercument Hapil, Fatma Z. Ertosun, Mustafa G. Ozturk, Saffet Griffith, Thomas S. Sanlioglu, Salih Sanlioglu, Ahter D. TI Tracing of islet graft survival by way of in vivo fluorescence imaging SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE EGFP; in vivo imaging; adenovirus; type 1 diabetes; xenogeneic islet transplantation ID TYPE-1 DIABETES-MELLITUS; LUNG-CANCER CELLS; PROSTATE CARCINOMA-CELLS; TRANSPLANTED ISLETS; ADENOVIRUS DELIVERY; APOPTOSIS; PROTEIN; TUMORS; TRAIL; GREEN AB Background To increase the success rate in xenogeneic islet transplantation, proper assessment of graft mass is required following transplantation. For this reason, we aimed to develop a suitable fluorescence imaging system to monitor islet xenograft survival in diabetic mice. Methods Adenovirus vector encoding enhanced green fluorescent protein-transduced rat pancreatic islets were transplanted under the renal capsule of streptozotocin-induced diabetic mice and the fluorescence signal was quantified over time using a cooled charge-coupled device. Non-fasting blood glucose levels were recorded during the same period. Insulin release from transduced and control islets was detected via enzyme-linked immunosorbent assay. Results Adenovirus vector encoding enhanced green fluorescent protein infection did not alter the function or survival of pancreatic islets post transduction. A direct correlation was found between the number of islets (250-750) transplanted under the kidney capsule and the blood glucose recovery. Conclusions Fluorescence imaging appears to be a useful tool for quantitative assessment of islet cell viability post transplantation and could permit earlier detection of graft rejection. Copyright. (C) 2011 John Wiley & Sons, Ltd. C1 [Kahraman, Sevim; Hapil, Fatma Z.; Ertosun, Mustafa G.; Sanlioglu, Salih; Sanlioglu, Ahter D.] Univ Hosp & Clin, Human Gene & Cell Therapy Ctr Akdeniz, Dept Med Biol & Genet, TR-07058 Antalya, Turkey. [Dirice, Ercument] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Med, Boston, MA 02215 USA. [Ozturk, Saffet] Akdeniz Univ, Fac Med, Dept Histol & Embryol, TR-07058 Antalya, Turkey. [Griffith, Thomas S.] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA. [Griffith, Thomas S.] Univ Iowa, Ctr Gene Therapy, Iowa City, IA 52242 USA. RP Sanlioglu, AD (reprint author), Univ Hosp & Clin, Human Gene & Cell Therapy Ctr Akdeniz, Dept Med Biol & Genet, TR-07058 Antalya, Turkey. EM ahter@akdeniz.edu.tr RI Ozturk, Saffet/C-1239-2016; Sanlioglu, Ahter/C-6504-2016; Sanlioglu, Salih/F-9305-2016; Dirice, Ercument/B-2825-2017; OI Sanlioglu, Ahter/0000-0003-4504-0375; Kahraman, Sevim/0000-0002-2880-6589 FU Akdeniz University Scientific Research Administration Division; Scientific and Technological Research Council of Turkey (TUBITAK) FX This work is supported by grants from Akdeniz University Scientific Research Administration Division and the Scientific and Technological Research Council of Turkey (TUBITAK). NR 43 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD SEP PY 2011 VL 27 IS 6 BP 575 EP 583 DI 10.1002/dmrr.1216 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824BZ UT WOS:000295176500007 PM 21584921 ER PT J AU Chan, CWH Tam, W Cheng, KKF Chui, YY So, WKW Mok, T Wong, C McReynolds, J Berry, DL AF Chan, Carmen W. H. Tam, Wilson Cheng, Karis K. F. Chui, Ying Yu So, Winnie K. W. Mok, Tony Wong, Connie McReynolds, Justin Berry, Donna L. TI Piloting electronic self report symptom assessment - Cancer (ESRA-C) in Hong Kong: A mixed method approach SO EUROPEAN JOURNAL OF ONCOLOGY NURSING LA English DT Article DE Electronic symptom assessment; Self report; Oncology; Feasibility; Acceptability; Chinese patients; Hong Kong ID QUALITY-OF-LIFE; PATIENT HEALTH QUESTIONNAIRE-9; COMPUTERIZED PROGRAM; ONCOLOGY PRACTICE; SOCIAL SUPPORT; PRIME-MD; VALIDATION; PAIN; SATISFACTION; FEASIBILITY AB Purpose: The benefits of utilizing computerized assessment in clinical settings have been reported in studies over the last three decades and more recently in the oncology settings. This study aimed to assess the feasibility and acceptability of using an electronic self report symptom assessment tool among Chinese oncology patients. Methods and sample: The tool, developed by The University of Washington, Distributed Health Assessment and Intervention Research (DHAIR) group was translated into Chinese. The adapted web-based survey platform, the Electronic Self Report Assessment - Cancer (ESRA-C), was tested in a local cancer resource center in Hong Kong. Participants' perceptions of the acceptability and feasibility of the symptom assessment process were assessed using the Acceptability E-scale as well as observation and qualitative interview data. Demographic data were also collected through the touch screen computer system. A convenience sample of 30 (11 male and 19 female) oncology patients was recruited to use the touch-screen computer to assess participants' symptoms using ESRA-C. Results: The acceptability scale indicated moderately high acceptability in each subscale (mean score of 3.32-4.71). On average, participants took 17.5 min (SD: 8.9) to complete the ESRA-C. The qualitative interview data revealed that the majority (25 participants) asserted that the ESRA-C was useful and effective in reporting personal health conditions. Conclusions: The study suggested that electronic assessment can offer a feasible, attractive, and viable means of implementing regular and comprehensive symptom assessment, which can lead to better symptom management in cancer patients. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Chan, Carmen W. H.; Cheng, Karis K. F.; So, Winnie K. W.] Chinese Univ Hong Kong, Nethersole Sch Nursing, Hong Kong, Hong Kong, Peoples R China. [Tam, Wilson] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China. [Chui, Ying Yu] Hong Kong Baptist Hosp, Sch Nursing, Hong Kong, Hong Kong, Peoples R China. [Mok, Tony; Wong, Connie] Chinese Univ Hong Kong, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China. [McReynolds, Justin; Berry, Donna L.] Univ Washington, Sch Nursing, Washington, DC USA. [Berry, Donna L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA USA. RP Chan, CWH (reprint author), Chinese Univ Hong Kong, Nethersole Sch Nursing, Hong Kong, Hong Kong, Peoples R China. EM whchan@cuhk.edu.hk RI So, Winnie/A-3994-2015; Chan, Carmen/A-4480-2015; OI Tam, Wilson/0000-0003-0641-3060 NR 42 TC 2 Z9 2 U1 5 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1462-3889 J9 EUR J ONCOL NURS JI Eur. J. Oncol. Nurs. PD SEP PY 2011 VL 15 IS 4 BP 325 EP 334 DI 10.1016/j.ejon.2010.10.002 PG 10 WC Oncology; Nursing SC Oncology; Nursing GA 823GO UT WOS:000295110700006 PM 21093371 ER PT J AU Gamer, LW Tsuji, K Cox, K Capelo, LP Lowery, J Beppu, H Rosen, V AF Gamer, Laura W. Tsuji, Kunikazu Cox, Karen Capelo, Luciane P. Lowery, Jonathan Beppu, Hideyuki Rosen, Vicki TI BMPR-II is Dispensable for Formation of the Limb Skeleton SO GENESIS LA English DT Article ID GENE-EXPRESSION; BONE-FORMATION; RECEPTOR; MOUSE; OSTEOBLASTS; GENERATION; CARTILAGE; IA AB Initiation of BMP signaling is dependent upon activation of Type I BMP receptor by constitutively active Type II BMP receptor. Three Type II BMP receptors have been identified; Acvr2a and Acvr2b serve as receptors for BMPs and for activin-like ligands whereas BMPR-II functions only as a BMP receptor. As BMP signaling is required for endochondral ossification and loss of either Acvr2a or Acvr2b is not associated with deficits in limb development, we hypothesized that BMPR-II would be essential for BMP signaling during skeletogenesis. We removed BMPR-II from early limb mesoderm by crossing BMPR-II floxed mice with those carrying the Prx1-Cre transgene. Mice lacking limb expression of BMPR-II have normal skeletons that could not be distinguished from control littermates. From these data, we conclude that BMPR-II is not required for endochondral ossification in the limb where loss of BMPR-II may be compensated by BMP utilization of Acvr2a and Acvr2b. genesis 49: 719-724, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Gamer, Laura W.; Cox, Karen; Capelo, Luciane P.; Lowery, Jonathan; Rosen, Vicki] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Tsuji, Kunikazu] Tokyo Med & Dent Univ, Dept Orthoped Surg, Tokyo, Japan. [Beppu, Hideyuki] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Gamer, LW (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM laura_gamer@hsdm.harvard.edu RI Capelo, Luciane/E-8756-2012 NR 24 TC 9 Z9 9 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-954X J9 GENESIS JI Genesis PD SEP PY 2011 VL 49 IS 9 BP 719 EP 724 DI 10.1002/dvg.20761 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 825GP UT WOS:000295259500003 PM 21538804 ER PT J AU Harris, NL Kluin, P AF Harris, Nancy Lee Kluin, Philip TI Follicular lymphoma grade 3B: is it a real disease? SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Editorial Material ID BCL6 TRANSLOCATION; CLINICAL-FEATURES; HISTOLOGIC GRADE; CELL LYMPHOMA; T(14/18); EXPRESSION; PROFILES; PROLIFERATION; ANTHRACYCLINE; REARRANGEMENT C1 [Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kluin, Philip] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM nlharris@partners.org NR 24 TC 4 Z9 5 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD SEP PY 2011 VL 96 IS 9 BP 1244 EP 1246 DI 10.3324/haematol.2011.050930 PG 3 WC Hematology SC Hematology GA 824RK UT WOS:000295219500003 PM 21880639 ER PT J AU Suter, MJ Nadkarni, SK Weisz, G Tanaka, A Jaffer, FA Bouma, BE Tearney, GJ AF Suter, Melissa J. Nadkarni, Seemantini K. Weisz, Giora Tanaka, Atsushi Jaffer, Farouc A. Bouma, Brett E. Tearney, Guillermo J. TI Intravascular Optical Imaging Technology for Investigating the Coronary Artery SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE intracoronary; optical diagnostics; optical imaging ID NEAR-INFRARED SPECTROSCOPY; LASER-INDUCED FLUORESCENCE; SIROLIMUS-ELUTING STENT; COHERENCE TOMOGRAPHY FINDINGS; FIBROUS CAP THICKNESS; IN-VIVO DETECTION; ATHEROSCLEROTIC PLAQUES; RAMAN-SPECTROSCOPY; VULNERABLE PLAQUE; REAL-TIME AB There is an ever-increasing demand for new imaging methods that can provide additional information about the coronary wall to better characterize and stratify high-risk plaques, and to guide interventional and pharmacologic management of patients with coronary artery disease. While there are a number of imaging modalities that facilitate the assessment of coronary artery pathology, this review paper focuses on intravascular optical imaging modalities that provide information on the microstructural, compositional, biochemical, biomechanical, and molecular features of coronary lesions and stents. The optical imaging modalities discussed include angioscopy, optical coherence tomography, polarization sensitive-optical coherence tomography, laser speckle imaging, near-infrared spectroscopy, time-resolved laser induced fluorescence spectroscopy, Raman spectroscopy, and near-infrared fluorescence molecular imaging. Given the wealth of information that these techniques can provide, optical imaging modalities are poised to play an increasingly significant role in the evaluation of the coronary artery in the future. (J Am Coll Cardiol Img 2011;4:1022-39) (C) 2011 by the American College of Cardiology Foundation C1 [Suter, Melissa J.; Nadkarni, Seemantini K.; Tanaka, Atsushi; Jaffer, Farouc A.; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Suter, Melissa J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Nadkarni, Seemantini K.; Tanaka, Atsushi; Bouma, Brett E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Weisz, Giora] Columbia Univ, Ctr Intervent Vasc Therapy, New York Presbyterian Hosp, New York, NY USA. [Weisz, Giora] Cardiovasc Res Fdn, New York, NY USA. [Jaffer, Farouc A.] Cardiovasc Res Ctr, Div Cardiol, Boston, MA USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 40 Blossom St,BAR 701, Boston, MA 02114 USA. EM gtearney@partners.org OI Jaffer, Farouc/0000-0001-7980-384X FU NCI NIH HHS [R00 CA134920, R00CA134920]; NHLBI NIH HHS [R21 HL089203, R01HL076398, R01 HL076398, R21HL088306, R01HL093717, R01 HL093717, R21 HL088306, R21HL089203] NR 154 TC 43 Z9 43 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD SEP PY 2011 VL 4 IS 9 BP 1022 EP 1039 DI 10.1016/j.jcmg.2011.03.020 PG 18 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 824FZ UT WOS:000295189100015 PM 21920342 ER PT J AU Leykum, LK Parekh, VI Sharpe, B Boonyasai, RT Centor, RM AF Leykum, Luci K. Parekh, Vikas I. Sharpe, Bradley Boonyasai, Romsai T. Centor, Robert M. TI Tried and True: A Survey of Successfully Promoted Academic Hospitalists SO JOURNAL OF HOSPITAL MEDICINE LA English DT Article DE academic hospital medicine; hospitalists; promotions process ID US MEDICAL-SCHOOLS; INTERNAL-MEDICINE; FACULTY; OPPORTUNITIES; CLINICIAN; EDUCATORS; TENURE; TIME AB BACKGROUND: Academic hospital medicine is a new and rapidly growing field. Hospitalist faculty members often fill roles not typically held by other academic faculty, maintain heavy clinical workloads, and participate in nontraditional activities. Because of these differences, there is concern about how academic hospitalists may fare in the promotions process. OBJECTIVE: To determine factors critical to the promotion of successfully promoted hospitalists who have achieved the rank of either associate professor or professor. DESIGN: A cross-sectional survey. PARTICIPANTS: Thirty-three hospitalist faculty members at 22 academic medical centers promoted to associate professor rank or higher between 1995 and 2008. MEASUREMENTS: Respondents were asked to describe their institution, its promotions process, and the activities contributing to their promotion. We identified trends across respondents. RESULTS: Twenty-six hospitalists responded, representing 20 institutions (79% response rate). Most achieved promotion in a nontenure track (70%); an equal number identified themselves as clinician-administrators and clinician educators (40%). While hospitalists were engaged in a wide range of activities in the traditional domains of service, education, and research, respondents considered peer-reviewed publication to be the most important activity in achieving promotion. Qualitative responses demonstrated little evidence that being a hospitalist was viewed as a hindrance to promotion. CONCLUSIONS: Successful promotion in academic hospital medicine depends on accomplishment in traditional academic domains, raising potential concerns for academic hospitalists with less traditional roles. This study may provide guidance for early-career academic hospitalists and program leaders. Journal of Hospital Medicine 2011;6:411-415. (C) 2011 Society of Hospital Medicine C1 [Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hosp Med, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Parekh, Vikas I.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. [Sharpe, Bradley] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Boonyasai, Romsai T.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD USA. [Centor, Robert M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. RP Leykum, LK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hosp Med, S Texas Vet Hlth Care Syst, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Leykum@uthscsa.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [01-091, REA 05-129]; American Board of Internal Medicine Foundation FX Dr. Leykum is supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (TRX #01-091 and REA 05-129). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs.; Dr. Boonyasai is supported by an Osler Center for Clinical Excellence faculty scholarship and by the American Board of Internal Medicine Foundation. NR 19 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD SEP PY 2011 VL 6 IS 7 BP 411 EP 415 DI 10.1002/jhm.894 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 824HR UT WOS:000295193500009 PM 21916004 ER PT J AU Axon, RN Cousineau, L Egan, BM AF Axon, R. Neal Cousineau, Laura Egan, Brent M. TI Prevalence and Management of Hypertension in the Inpatient Setting: A Systematic Review SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review DE disease prevention; epidemiology; hypertension ID BLOOD-PRESSURE; HOSPITALIZED-PATIENTS; HEART-DISEASE; PREVENTION; ADULTS; CARE; DISCHARGE; PATTERNS; THERAPY; IMPACT AB BACKGROUND: Hypertension (HTN) is a major cardiovascular risk factor yet control rates remain suboptimal. Thus, improving recognition, treatment, and control of HTN by focusing on novel populations such as hospitalized patients is warranted. Current consensus guidelines do not address inpatient HTN, and little is known about HTN prevalence or patterns of care in this setting. METHODS: We conducted a systematic review of English-language studies published in 1976 or later that reported on HTN prevalence and care patterns among adult inpatients. We included MEDLINE-indexed randomized-controlled trials, meta-analyse:3, and observational studies that: (1) reported estimates of the prevalence of HTN in the inpatient setting, and (2) used HTN diagnosis or treatment as a primary focus. We excluded randomized, controlled trials that recorded measures of inpatient blood pressure but whose focus was not HTN. RESULTS: We identified 9 studies meeting inclusion criteria, and in those studies, HTN was highly prevalent among inpatients, ranging from 50.5% to 72%. Intensification of antihypertensive treatment was inconsistent, and 37% to 77% of hypertensive patients remained hypertensive at the time of discharge. Most patients with inpatient HTN continued to have elevated blood pressures at outpatient follow-up. CONCLUSIONS: Inpatient HTN is prevalent and a large percentage of those with this condition remain hypertensive at the time of discharge and at follow-up. The potential exists for improved recognition and treatment of newly diagnosed and known, but uncontrolled, HTN observed in the inpatient setting. Journal of Hospital Medicine 2011;6:417-422. (C) 2010 Society of Hospital Medicine. C1 [Axon, R. Neal; Egan, Brent M.] Med Univ S Carolina, Dept Internal Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Axon, R. Neal] Ralph H Johnson VAMC, Med Serv, Charleston, SC USA. [Axon, R. Neal] Ralph H Johnson VAMC, Res Serv, Charleston, SC USA. [Cousineau, Laura] MUSC Lib & Educ Ctr, Charleston, SC USA. RP Axon, RN (reprint author), 96 Jonathon Lucas St,POB 250623, Charleston, SC 29425 USA. EM axon@musc.edu NR 30 TC 7 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD SEP PY 2011 VL 6 IS 7 BP 417 EP 422 DI 10.1002/jhm.804 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 824HR UT WOS:000295193500010 PM 20652961 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Smoking and Outcomes After Knee and Hip Arthroplasty: A Systematic Review SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE SMOKING; ARTHROPLASTY; OUTCOMES; TOTAL KNEE ARTHROPLASTY; TOTAL HIP ARTHROPLASTY ID DEEP-VEIN THROMBOSIS; BODY-MASS INDEX; QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; POSTOPERATIVE COMPLICATIONS; RISK-FACTORS; CESSATION INTERVENTION; JOINT REPLACEMENT; CIGARETTE-SMOKING; PREDICTORS AB Objective. Studies have suggested higher rates of perioperative and postoperative complications in smokers compared to nonsmokers. The objective of this systematic review was to assess the association of smoking and postoperative outcomes following total hip arthroplasty (THA) or total knee arthroplasty (TKA). Methods. A search of 6 databases (The Cochrane Library, Scopus, Proquest Dissertation abstracts, CINAHL, Ovid Medline, and Embase) was performed by a Cochrane librarian. All titles and abstracts were screened by 2 independent reviewers with expertise in performing systematic reviews. Studies were included if they were fully published reports that included smoking and any perioperative or postoperative clinical outcome in patients with TKA or THA. Results. A total of 21 studies were included for the review, of which 6 provided multivariable-adjusted analyses, 14 univariate analyses, and one statistical modeling. For most outcomes, results from 1-2 studies could be pooled. Current smokers were significantly more likely to have any postoperative complication (risk ratio 1.24, 95% CI 1.01 to 1.54) and death (risk ratio 1.63, 95% CI 1.06 to 2.51) compared to nonsmokers. Former smokers were significantly more likely to have any post-operative complication (risk ratio 1.32,95% CI 1.05 to 1.66) and death (risk ratio 1.69,95% CI 1.08 to 2.64) compared to nonsmokers. Conclusion. This systematic review found that smoking is associated with significantly higher risk of postoperative complication and mortality following TKA or THA. Studies examining longterm consequences of smoking on implant survival and complications are needed. Smoking cessation may improve outcomes after THA or TKA. (First Release June 1 2011; J Rheumatol 2011;38:1824-34;doi:10.3899/jrheum.101221) C1 [Singh, Jasvinder A.] Univ Alabama, Med Serv, Birmingham Vet Affairs VA Med Ctr, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Hlth Sci Res, Rochester, MN USA. [Singh, Jasvinder A.] Mayo Clin, Sch Med, Dept Orthoped Surg, Rochester, MN USA. [Singh, Jasvinder A.] VA Med Ctr, Med Serv, Minneapolis, MN USA. [Singh, Jasvinder A.] Univ Minnesota, Minneapolis, MN USA. RP Singh, JA (reprint author), Univ Alabama, Med Serv, Birmingham Vet Affairs VA Med Ctr, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU National Institutes of Health (NIH) [1 KL2 RR024151-01] FX Supported by National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research). NR 68 TC 32 Z9 33 U1 3 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 2011 VL 38 IS 9 BP 1824 EP 1834 DI 10.3899/jrheum.101221 PG 11 WC Rheumatology SC Rheumatology GA 824FS UT WOS:000295188400004 PM 21632674 ER PT J AU Lanzman, RS Winter, J Blondin, D Furst, G Scherer, A Miese, FR Abbara, S Kropil, P AF Lanzman, Rotem S. Winter, Joachim Blondin, Dirk Fuerst, Guenter Scherer, Axel Miese, Falk R. Abbara, Suhny Kroepil, Patric TI Where Does It Lead? Imaging Features of Cardiovascular Implantable Electronic Devices on Chest Radiograph and CT SO KOREAN JOURNAL OF RADIOLOGY LA English DT Editorial Material DE Pacemaker; ICD; Chest; Radiograph; CT ID CARDIOVERTER-DEFIBRILLATOR; PACEMAKER THERAPY; COMPLICATIONS; FAILURE; SYSTEMS; PERFORATION; MANAGEMENT; MORBIDITY; OPERATION AB Pacemakers and implantable cardioverter defibrillators (ICDs) are being increasingly employed in patients suffering from cardiac rhythm disturbances. The principal objective of this article is to familiarize radiologists with pacemakers and ICDs on chest radiographs and CT scans. Therefore, the preferred lead positions according to pacemaker types and anatomic variants are introduced in this study. Additionally, the imaging features of incorrect lead positions and defects, as well as complications subsequent to pacemaker implantation are demonstrated herein. C1 [Lanzman, Rotem S.; Blondin, Dirk; Fuerst, Guenter; Scherer, Axel; Miese, Falk R.; Kroepil, Patric] Univ Dusseldorf, Fac Med, Dept Diagnost & Intervent Radiol, D-40225 Dusseldorf, Germany. [Winter, Joachim] Univ Hosp Dusseldorf, Dept Cardiovasc Surg, D-40225 Dusseldorf, Germany. [Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kropil, P (reprint author), Univ Hosp Dusseldorf, Dept Diagnost & Intervent Radiol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM pkroepil@gmx.de NR 24 TC 5 Z9 5 U1 0 U2 2 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 J9 KOREAN J RADIOL JI Korean J. Radiol. PD SEP-OCT PY 2011 VL 12 IS 5 BP 611 EP 619 DI 10.3348/kjr.2011.12.5.611 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 823II UT WOS:000295115300011 PM 21927563 ER PT J AU Auwaerter, PG Bakken, JS Dattwyler, RJ Dumler, JS Halperin, JJ McSweegan, E Nadelman, RB O'Connell, S Shapiro, ED Sood, SK Steere, AC Weinstein, A Wormser, GP AF Auwaerter, Paul G. Bakken, Johan S. Dattwyler, Raymond J. Dumler, J. Stephen Halperin, John J. McSweegan, Edward Nadelman, Robert B. O'Connell, Susan Shapiro, Eugene D. Sood, Sunil K. Steere, Allen C. Weinstein, Arthur Wormser, Gary P. TI Antiscience and ethical concerns associated with advocacy of Lyme disease SO LANCET INFECTIOUS DISEASES LA English DT Article ID PLACEBO-CONTROLLED TRIAL; BORRELIA-BURGDORFERI; ANTIBIOTIC-THERAPY; PERSISTENT SYMPTOMS; PRACTICE GUIDELINES; DOUBLE-BLIND; POLITICS; INFORMATION; DURATION; AMERICA AB Advocacy for Lyme disease has become an increasingly important part of an antiscience movement that denies both the viral cause of AIDS and the benefits of vaccines and that supports unproven (sometimes dangerous) alternative medical treatments. Some activists portray Lyme disease, a geographically limited tick-borne infection, as a disease that is insidious, ubiquitous, difficult to diagnose, and almost incurable; they also propose that the disease causes mainly non-specific symptoms that can be treated only with long-term antibiotics and other unorthodox and unvalidated treatments. Similar to other antiscience groups, these advocates have created a pseudoscientific and alternative selection of practitioners, research, and publications and have coordinated public protests, accused opponents of both corruption and conspiracy, and spurred legislative efforts to subvert evidence-based medicine and peer-reviewed science. The relations and actions of some activists, medical practitioners, and commercial bodies involved in Lyme disease advocacy pose a threat to public health. C1 [Auwaerter, Paul G.] Johns Hopkins Med Inst, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. [Dumler, J. Stephen] Johns Hopkins Med Inst, Div Med Microbiol, Dept Pathol, Baltimore, MD 21205 USA. [Bakken, Johan S.] St Lukes Hosp, Infect Dis Sect, Duluth, MN USA. [Dattwyler, Raymond J.] New York Med Coll, Dept Med, Div Allergy Immunol & Rheumatol, Valhalla, NY 10595 USA. [Nadelman, Robert B.; Wormser, Gary P.] New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA. [Halperin, John J.] Atlantic Neurosci Inst, Summit, NJ USA. [Halperin, John J.] Mt Sinai Sch Med, New York, NY USA. [O'Connell, Susan] Southampton Gen Hosp, Lyme Borreliosis Unit, Hlth Protect Agcy, Microbiol Lab, Southampton SO9 4XY, Hants, England. [Shapiro, Eugene D.] Yale Univ, Dept Pediat, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Shapiro, Eugene D.] Yale Univ, Dept Invest Med, New Haven, CT 06520 USA. [Sood, Sunil K.] Cohen Childrens Med Ctr, Div Pediat Infect Dis, Manhasset, NY USA. [Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Weinstein, Arthur] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Weinstein, Arthur] Washington Hosp Ctr, Rheumatol Sect, Dept Med, Washington, DC 20010 USA. RP Auwaerter, PG (reprint author), Johns Hopkins Med Inst, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. EM pgauwaerter@gmail.com OI Dattwyler, Raymond/0000-0002-1983-1301 FU NIH/Immunetics; BioRad; DiaSorin; BioMerieux; National Center for Research Resources (NCRR; a component of the NIH) [K24 RR022477, KL2 RR024138, UL1 RR024139]; NIH Roadmap for Medical Research FX PGA has served as a consultant for Oxford Diagnostics and has participated in expert testimony in two medicolegal suits about possible Lyme disease. He has equity interest in Johnson & Johnson, no products of which are referred to in this article. RJD is part owner of and has stock in Biopeptides Corporation, no product of which is referred to in this article, has received payment for providing expert testimony in malpractice cases and holds patents on vaccine and diagnostic technology with SUNY at Stony Brook Biopeptides. JSD has received support for travel to meetings from DiaSorin and has licence of US patent 5,955,359 to Focus Diagnostics; none of these declarations are directly related to the contents of this article. JJH has served as an expert witness in several medicolegal cases concerning Lyme disease and has equity in Abbott, Bristol-Myers Squibb, Johnson & Johnson, and Merck; no products from these companies are referred to in this article. EMcS was a former programme officer for Lyme disease at the US NIH. RBN has served as an expert witness in malpractice litigation involving Lyme disease. EDS is a board member of the American Lyme Disease Foundation, for which no compensation is received. He has reviewed medical records for the Metropolitan Life Insurance Company and has provided medicolegal testimony. GPW is a board member of the American Lyme Disease Foundation for which no compensation is received, has served as an expert witness in malpractice cases involving Lyme disease, has research grants from the NIH/Immunetics, BioRad, DiaSorin, and BioMerieux to study diagnostic tests for Lyme disease, none of which is mentioned in the manuscript, and has equity in Abbott, a company not known to have any approved product for Lyme disease. JSB, RJD, JSD, JJH, RBN, EDS, ACS, and GPW have served on the panel for the 2006 IDSA Lyme disease guidelines. JSB, SO'C, SKS, ACS, and AW declare that they have no conflicts of interest.; We thank Lenise Banwarie and Diana Olson for their assistance. EDS is supported in part by grant K24 RR022477 and Clinical and Translational Science Award (CTSA) grants KL2 RR024138 and UL1 RR024139 from the National Center for Research Resources (NCRR; a component of the NIH) and the NIH Roadmap for Medical Research. The contents of the article are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or the NIH. NR 66 TC 40 Z9 40 U1 1 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2011 VL 11 IS 9 BP 713 EP 719 PG 7 WC Infectious Diseases SC Infectious Diseases GA 824YY UT WOS:000295239300026 PM 21867956 ER PT J AU Buonanno, FS Spence, JD AF Buonanno, Ferdinando S. Spence, J. David TI Short-acting nifedipine and risk of stroke SO NEUROLOGY LA English DT Editorial Material ID HYPERTENSION C1 [Spence, J. David] Univ Western Ontario, Stroke Prevent & Atherosclerosis Res Ctr, Robarts Res Inst, London, ON N6G 2V2, Canada. [Buonanno, Ferdinando S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv,Dept Neurol, Boston, MA USA. RP Spence, JD (reprint author), Univ Western Ontario, Stroke Prevent & Atherosclerosis Res Ctr, Robarts Res Inst, 1400 Western Rd, London, ON N6G 2V2, Canada. EM dspence@robarts.ca RI Spence, J. David/K-6396-2013 OI Spence, J. David/0000-0001-7478-1098 NR 10 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 2011 VL 77 IS 13 BP 1216 EP 1217 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 825EM UT WOS:000295253800005 PM 21849658 ER PT J AU Giles, MF Albers, GW Amarenco, P Arsava, EM Asimos, AW Ay, H Calvet, D Coutts, SB Cucchiara, BL Demchuk, AM Johnston, SC Kelly, PJ Kim, AS Labreuche, J Lavallee, PC Mas, JL Merwick, A Olivot, JM Purroy, F Rosamond, WD Sciolla, R Rothwell, PM AF Giles, M. F. Albers, G. W. Amarenco, P. Arsava, E. M. Asimos, A. W. Ay, H. Calvet, D. Coutts, S. B. Cucchiara, B. L. Demchuk, A. M. Johnston, S. C. Kelly, P. J. Kim, A. S. Labreuche, J. Lavallee, P. C. Mas, J. -L. Merwick, A. Olivot, J. M. Purroy, F. Rosamond, W. D. Sciolla, R. Rothwell, P. M. TI Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA A multicenter study SO NEUROLOGY LA English DT Article ID TRANSIENT ISCHEMIC ATTACK; MINOR STROKE; DIFFUSION; METAANALYSIS; POPULATION; PREDICT; LESIONS; DEFINITION; VALIDATION; INFARCTION AB Objectives: Stroke risk immediately after TIA defined by time-based criteria is high, and prognostic scores (ABCD2 and ABCD3-I) have been developed to assist management. The American Stroke Association has proposed changing the criteria for the distinction between TIA and stroke from time-based to tissue-based. Research using these definitions is lacking. In a multicenter observational cohort study, we have investigated prognosis and performance of the ABCD2 score in TIA, subcategorized as tissue-positive or tissue-negative on diffusion-weighted imaging (DWI) or CT imaging according to the newly proposed criteria. Methods: Twelve centers provided data on ABCD2 scores, DWI or CT brain imaging, and follow-up in cohorts of patients with TIA diagnosed by time-based criteria. Stroke rates at 7 and 90 days were studied in relation to tissue-positive or tissue-negative subcategorization, according to the presence or absence of brain infarction. The predictive power of the ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses. Results: A total of 4,574 patients were included. Among DWI patients (n = 3,206), recurrent stroke rates at 7 days were 7.1% (95% confidence interval 5.5-9.1) after tissue-positive and 0.4% (0.2-0.7) after tissue-negative events (p diff < 0.0001). Corresponding rates in CT-imaged patients were 12.8% (9.3-17.4) and 3.0% (2.0-4.2), respectively (p diff < 0.0001). The ABCD2 score had predictive value in tissue-positive and tissue-negative events (AUC = 0.68 [95% confidence interval 0.63-0.73] and 0.73 [0.67-0.80], respectively; p sig < 0.0001 for both results, p diff = 0.17). Tissue-positive events with low ABCD2 scores and tissue-negative events with high ABCD2 scores had similar stroke risks, especially after a 90-day follow-up. Conclusions: Our findings support the concept of a tissue-based definition of TIA and stroke, at least on prognostic grounds. Neurology (R) 2011; 77: 1222-1228 C1 [Giles, M. F.] Univ Oxford, John Radcliffe Hosp, Dept Clin Neurol, Stroke Prevent Res Unit,NIHR Biomed Res Ctr, Oxford OX3 9DU, England. [Albers, G. W.; Olivot, J. M.] Stanford Stroke Ctr, Dept Neurol & Neurol Sci, Palo Alto, CA USA. [Amarenco, P.; Labreuche, J.; Lavallee, P. C.] Bichat Claude Bernard Univ Hosp, Dept Neurol, Paris, France. [Amarenco, P.; Labreuche, J.; Lavallee, P. C.] Bichat Claude Bernard Univ Hosp, Stroke Ctr, Paris, France. [Arsava, E. M.; Ay, H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Arsava, E. M.; Ay, H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Asimos, A. W.] Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. [Calvet, D.; Mas, J. -L.] Ctr Hosp St Anne, Dept Neurol, Paris, France. [Coutts, S. B.; Demchuk, A. M.] Univ Calgary, Dept Radiol, Seaman Family Ctr, Calgary, AB, Canada. [Coutts, S. B.; Demchuk, A. M.] Univ Calgary, Dept Clin Neurosci, Seaman Family Ctr, Calgary, AB, Canada. [Cucchiara, B. L.] Univ Penn, Med Ctr, Dept Neurol, Philadelphia, PA 19104 USA. [Johnston, S. C.; Kim, A. S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Kelly, P. J.; Merwick, A.] Mater Univ Hosp, Neurovasc Clin Sci Unit, Dublin, Ireland. [Purroy, F.] Univ Lleida, Dept Neurol, Lleida, Spain. [Sciolla, R.] Univ Turin, Dept Neurol, Turin, Italy. [Rosamond, W. D.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. RP Giles, MF (reprint author), Univ Oxford, John Radcliffe Hosp, Dept Clin Neurol, Stroke Prevent Res Unit,NIHR Biomed Res Ctr, Level 6,West Wing, Oxford OX3 9DU, England. EM matthew.giles@clneuro.ox.ac.uk RI Purroy, Francisco/D-4538-2009; Arsava, Ethem Murat/I-9197-2013; Merwick, Aine/L-9754-2013; Demchuk, Andrew/E-1103-2012; OI Arsava, Ethem Murat/0000-0002-6527-4139; Merwick, Aine/0000-0001-7533-0117; Demchuk, Andrew/0000-0002-4930-7789; Purroy, Francisco/0000-0002-1808-5968 FU NIHR; Boehringer Ingelheim; National Institute of Health Research; Genentech, Inc.; NIH; Bristol-Myers Squibb; Pfizer Inc; Merck Serono; AstraZeneca; sanofi-aventis; PHRC; CIHR; Alberta-Innovates-Health Solutions; Heart and Stroke Foundation of Canada; American Heart Association; American Stroke Association; Novo Nordisk; NIH/NINDS; NIH (NCRR, NINDS); Servier; French Ministry of Health; INSERM Institut National Scientifique et de la Recherche Medicale; Lundbeck Inc.; Health Research Board of Ireland; Ministerio de Sanidad y Consumo; Instituto de Salud Carlos III; CDC; Bayer Schering Pharma FX P. M. R. has an NIHR Senior Fellowship.; Dr. Giles has received funding for travel and speaker honoraria from Boehringer Ingelheim and has received research support from National Institute of Health Research. Dr. Albers serves on a scientific advisory board for Lundbeck Inc.; has received funding for travel or speaker honoraria from Genentech, Inc.; serves on the editorial board of Stroke; serves as a consultant for Bristol-Myers Squibb, Merck Serono, Arbor Vita Corporation, AstraZeneca, and Mitsubishi Tanabe Pharma Corporation; receives research support from the NIH; and has served as an expert witness in medico-legal cases. Dr. Amarenco serves on scientific advisory boards for and has received funding for travel and speaker honoraria from Bristol-Myers Squibb, Pfizer Inc, Merck Serono, AstraZeneca, sanofi-aventis, and Boehringer Ingelheim; serves as Associate Editor, Europe for Stroke; and receives research support from sanofi-aventis, Bristol-Myers Squibb, Merck Serono, AstraZeneca, and PHRC. Dr. Arsava reports no disclosures. Dr. Asimos receives research support from Boehringer Ingelheim. Dr. Ay serves on the editorial boards of Stroke and Cerebrovascular Diseases and receives research support from the NIH. Dr. Calvet reports no disclosures. Dr. Coutts receives research support from Pfizer Inc, CIHR, Alberta-Innovates-Health Solutions, and a Heart and Stroke Foundation of Canada's Distinguished Clinician Scientist award, supported in partnership with the CIHR, Institute of Circulatory and Respiratory Health, and AstraZeneca. Dr. Cucchiara serves on a data safety monitoring board for Wyeth; has received speaker honoraria from Boehringer Ingelheim and diaDexus, Inc.; has received publishing royalties from UpToDate, Inc.; serves as a consultant for Ferrer, diaDexus, Inc., and iNova Pharmaceuticals; and receives research support from the NIH, the American Heart Association, and the American Stroke Association. Dr. Demchuk served on scientific advisory boards for Boehringer Ingelheim and Bayer Schering Pharma; has received funding for travel from sanofi-aventis; serves on the editorial boards of Journal of Neuroimaging, Stroke, and the International Journal of Stroke; has received speaker honoraria from Boehringer Ingelheim; receives research support from Novo Nordisk, the NIH/NINDS, and the CIHR; and owns stock in Calgary Scientific, Inc. Dr. Johnston is co-holder of patent re: the RNA panel to identify TIA and risk stratify and receives research support from sanofi-aventis, Strkyer Neurovascular, Boston Scientific, the NIH (NCRR, NINDS), Kaiser-Permanente, and AHA/ASA Bugher Award. Dr. Kelly has received research support to his institution from Pfizer Inc, Servier, and Bristol-Myers Squibb and has received research support from the Health Research Board of Ireland and the Irish Heart Foundation. Dr. Kim receives research support from the NIH (NCRR, NINDS), the American Heart Association, and the National Stroke Association. J. Labreuche and Dr. Lavallee report no disclosures. Dr. Mas serves on scientific advisory boards for AstraZeneca, Bayer Schering Pharma, Boehringer Ingelheim, sanofi-aventis/Bristol-Myers Squibb, Servier, and Takeda Pharmaceutical Company Limited; has received research support from Boehringer Ingelheim, sanofi-aventis, and Servier; and receives research support from sanofi-aventis, the French Ministry of Health, and INSERM Institut National Scientifique et de la Recherche Medicale. Dr. Merwick has received research support from Pfizer Inc, Lundbeck Inc., and Boehringer Ingelheim and receives salary support from the Health Research Board of Ireland. Dr.; livot reports no disclosures. Dr. Purroy received research support from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III. Dr. Rosamond receives research support from the CDC and the NIH. Dr. Sciolla reports no disclosures. Prof. Rothwell serves on scientific advisory boards for Bayer Schering Pharma, Servier, Pfizer Inc, and Biotronic; has received funding for travel from sanofi- aventis, Servier, AstraZeneca, and Bayer Schering Pharma; and serves on the editorial boards of Lancet Neurology, Stroke, and Cerebrovascular Diseases and as Assistant Editor for the International Journal of Stroke. NR 40 TC 62 Z9 65 U1 5 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 SEP PY 2011 VL 77 IS 13 BP 1222 EP 1228 DI 10.1212/WNL.0b013e3182309f91 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 825EM UT WOS:000295253800008 PM 21865578 ER PT J AU Hunter, DJ Guermazi, A Lo, GH Grainger, AJ Conaghan, PG Boudreau, RM Roemer, FW AF Hunter, D. J. Guermazi, A. Lo, G. H. Grainger, A. J. Conaghan, P. G. Boudreau, R. M. Roemer, F. W. TI Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score) (vol 19, pg 990, 2011) SO OSTEOARTHRITIS AND CARTILAGE LA English DT Correction C1 [Hunter, D. J.] Univ Sydney, Royal N Shore Hosp, Dept Rheumatol, No Clin Sch, Sydney, NSW 2065, Australia. [Guermazi, A.; Roemer, F. W.] Boston Univ, Sch Med, Dept Radiol, QIC, Boston, MA 02118 USA. [Lo, G. H.] Michael E DeBakey Vet Adm Med Ctr, Houston Hlth Serv Res & Dev HSR&D Ctr Excellence, Houston, TX USA. [Lo, G. H.] Baylor Coll Med, Dept Med, Sect Immunol Allergy & Rheumatol, Houston, TX 77030 USA. [Grainger, A. J.] Leeds Teaching Hosp, Dept Radiol, Leeds, W Yorkshire, England. [Grainger, A. J.; Conaghan, P. G.] NIHR Leeds Musculoskeletal Biomed Res Unit, Leeds, W Yorkshire, England. [Conaghan, P. G.] Univ Leeds, Sect Musculoskeletal Dis, Leeds, W Yorkshire, England. [Boudreau, R. M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Roemer, F. W.] Klinikum Augsburg, Dept Radiol, Augsburg, Germany. RP Hunter, DJ (reprint author), Univ Sydney, Royal N Shore Hosp, Dept Rheumatol, No Clin Sch, Sydney, NSW 2065, Australia. EM David.Hunter@sydney.edu.au RI Hunter, David/A-4622-2010 OI Hunter, David/0000-0003-3197-752X NR 1 TC 2 Z9 2 U1 0 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2011 VL 19 IS 9 BP 1168 EP 1168 DI 10.1016/j.joca.2011.08.001 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 825CL UT WOS:000295248400015 ER PT J AU Mullins, RJ Clark, S Katelaris, C Smith, V Solley, G Camargo, CA AF Mullins, Raymond James Clark, Sunday Katelaris, Constance Smith, Victoria Solley, Graham Camargo, Carlos A., Jr. TI Season of birth and childhood food allergy in Australia SO PEDIATRIC ALLERGY AND IMMUNOLOGY LA English DT Article DE epidemiology; vitamin D; food allergy; birth season; sunlight ID VITAMIN-D; REGIONAL-VARIATION; SENSITIZATION; PRESCRIPTIONS; PREVALENCE; HYPERSENSITIVITY; LATITUDE; INFANCY; PEANUT; COHORT AB Background: Recent studies suggest a possible role for low ultraviolet radiation exposure and low vitamin D status as a risk factor for food allergy. We hypothesized that children born in autumn/winter months (less sun exposure) might have higher food allergy rates than those born in spring/summer. Methods: We compared IgE-mediated food allergy rates by season of birth in 835 children aged 0-4 yr assessed 1995-2009 in a specialist referral clinic, using population births as controls. To address potential concerns about generalizability, we also examined national prescriptions for adrenaline autoinjectors (2007) and infant hypoallergenic formula (2006-2007). Results: Although live births in the general ACT population showed no seasonal pattern (50% autumn/winter vs. 50% spring/summer), autumn/winter births were more common than spring/summer births among food allergy patients (57% vs. 43%; p < 0.001). The same seasonal pattern was observed with peanut (60% vs. 40%; p < 0.001) and egg (58% vs. 42%; p = 0.003). Regional UVR intensity was correlated with relative rate of overall food allergy (beta, -1.83; p = 0.05) and peanut allergy (beta, -3.27; p = 0.01). National data showed that autumn/winter births also were more common among children prescribed EpiPens (54% vs. 46%; p < 0.001) and infant hypoallergenic formula (54% vs. 46%; p < 0.001). Conclusions: The significantly higher rates of food allergy in children born autumn/winter (compared to spring/summer), the relationship between relative food allergy rates and monthly UVR, combined with national adrenaline autoinjector and infant hypoallergenic formula prescription data, suggest that ultraviolet light exposure/vitamin D status may be one of many potential factors contributing to childhood food allergy pathogenesis. C1 [Mullins, Raymond James] John James Med Ctr, Deakin, ACT 2600, Australia. [Mullins, Raymond James] Australian Natl Univ, Sch Med, Canberra, ACT, Australia. [Mullins, Raymond James] Univ Canberra, Fac Hlth, Canberra, ACT 2601, Australia. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Katelaris, Constance] Univ Western Sydney, Dept Med, Sydney, NSW, Australia. [Smith, Victoria] Rose Cottage Med Ctr, Launceston, Tas, Australia. [Solley, Graham] Watkins Med Ctr, Brisbane, Qld, Australia. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Mullins, RJ (reprint author), John James Med Ctr, Suite 1,175 Strickland Crescent, Deakin, ACT 2600, Australia. EM rmullins@allergycapital.com.au RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Mullins, Raymond/0000-0002-0267-1591 FU Commonwealth Serum Laboratories Australia; Alphapharm Australia; Abbott Nutrition Australia and the Ilhan Food Allergy Foundation FX We thank Vanna Mabbott (DOHA) for provision of additional EpiPen-related data and Louise Freebairn, Epidemiology Branch, ACT Health, for provision of ACT birth month data. Data purchase was funded with unrestricted investigator-initiated grants from Commonwealth Serum Laboratories Australia and Alphapharm Australia (the past and current Australian distributors of EpiPen), Abbott Nutrition Australia and the Ilhan Food Allergy Foundation. Study sponsors had no input into study design, data interpretation or the contents of this manuscript. NR 31 TC 45 Z9 47 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0905-6157 J9 PEDIAT ALLERG IMM-UK JI Pediatr. Allergy Immunol. PD SEP PY 2011 VL 22 IS 6 BP 583 EP 589 DI 10.1111/j.1399-3038.2011.01151.x PG 7 WC Allergy; Immunology; Pediatrics SC Allergy; Immunology; Pediatrics GA 823AM UT WOS:000295093200008 PM 21342281 ER PT J AU Graber, CJ Shane, AL Weintrub, P Chambers, HF AF Graber, Christopher J. Shane, Andi L. Weintrub, Peggy Chambers, Henry F. TI Clonality of Staphylococcus aureus Colonization over Time in Attendees of a Camp for Children with Chronic Dermatoses SO PEDIATRIC DERMATOLOGY LA English DT Article ID SKIN INFECTIONS AB Chronic dermatoses are risk factors for Staphylococcus aureus colonization; little is known about the significance of transmission between persons with chronic dermatoses (CD) and their contacts. We collected nasal, axillary, and skin swabs for S. aureus from 50 attendees of a camp for children with CD and their families at three time points: start and end of 2005 camp and start of 2006 camp (times A, B, and C, respectively). Thirty-one persons had CD, including epidermolysis bullosa (n = 14), atopic dermatitis (n = 7), ichthyosis (n = 5), and psoriasis (n = 5). Methicillin susceptibility and genotype were determined for all S. aureus isolates. Seventy-one unique S. aureus isolate from 10 clonal complexes (CC) were isolated; 14 (20%) were methicillin-resistant (MRSA). Persons with CD were more likely than those without CD to be colonized with S. aureus at the start of the 2005 (p = 0.01) and 2006 (p = 0.02) camp or at any time or site (p = 0.04) or to be persistently colonized with the same S. aureus CC at the start and end of the 2005 camp. Persons with atopic dermatitis had the highest burden of S. aureus colonization, whereas MRSA was isolated most frequently from attendees with epidermolysis bullosa. Three hospitalizations for skin infections were noted in people with CD between the 2005 and 2006 camps, versus three hospitalizations in the 6 months before the 2005 camp. Although S. aureus colonization was frequent among camp attendees (and in persons with CD in particular), it was diverse and variable. Camp attendance did not appear to affect infection-related clinical outcomes. C1 [Graber, Christopher J.] VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA 90073 USA. [Graber, Christopher J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Graber, Christopher J.; Chambers, Henry F.] San Francisco Gen Hosp, Div Infect Dis, San Francisco, CA 94110 USA. [Graber, Christopher J.; Chambers, Henry F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shane, Andi L.] Emory Univ, Sch Med, Div Pediat Infect Dis, Atlanta, GA USA. [Shane, Andi L.; Weintrub, Peggy] Univ Calif San Francisco, Div Pediat Infect Dis, San Francisco, CA 94143 USA. RP Graber, CJ (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, 11301 Wilshire Blvd,111-F, Los Angeles, CA 90073 USA. EM cgraber@ucla.edu NR 14 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-8046 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD SEP-OCT PY 2011 VL 28 IS 5 BP 519 EP 523 DI 10.1111/j.1525-1470.2011.01508.x PG 5 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA 823BI UT WOS:000295096000006 PM 21895757 ER PT J AU Hamblin, MR AF Hamblin, Michael R. TI Reply to "Championing photoantimicrobial discovery" SO PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY LA English DT Letter ID PHOTODYNAMIC THERAPY; INFECTIONS C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1572-1000 J9 PHOTODIAGN PHOTODYN JI Photodiagnosis Photodyn. Ther. PD SEP PY 2011 VL 8 IS 3 BP 289 EP 290 DI 10.1016/j.pdpdt.2011.06.005 PG 2 WC Oncology SC Oncology GA 823FX UT WOS:000295109000010 ER PT J AU Rodriguez, KL Bayliss, NK Alexander, SC Jeffreys, AS Olsen, MK Pollak, KI Garrigues, SK Tulsky, JA Arnold, RM AF Rodriguez, Keri L. Bayliss, Nichole K. Alexander, Stewart C. Jeffreys, Amy S. Olsen, Maren K. Pollak, Kathryn I. Garrigues, Sarah K. Tulsky, James A. Arnold, Robert M. TI Effect of patient and patient-oncologist relationship characteristics on communication about health-related quality of life SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; patient-provider relationship; communication; quality of life ID PHYSICIAN RELATIONSHIP; DECISION-MAKING; CLINICAL-PRACTICE; CANCER-PATIENT; PREFERENCES; CHEMOTHERAPY; OUTCOMES; SCORES; TRIAL; TRUST AB Objective: To test the effects of patient and patient-oncologist relationship factors on the time spent communicating about health-related quality of life (HRQOL) during outpatient clinic encounters between oncologists and their patients with advanced cancer. Methods: Using mixed methods, we coded for duration of HRQOL talk in a subset of audio-recorded conversations from the Study of Communication in Oncologist-Patient Encounters (SCOPE) Trial. Multivariable linear regression modeling was used to investigate the relationship between duration of HRQOL talk and gender concordance, race concordance, patient education status, patient marital status, and length of the patient-oncologist relationship (i.e. number of previous visits). Results: Sixty-six encounters were analyzed that involved 63 patients and 34 oncologists. Patients were more likely to be female (51%), white (86%), married (78%), and possess a college or more advanced degree (33%). Most oncologists were male (82%) and white (82%). Mean ages were 58.8 years for patients and 44.9 years for oncologists. Regression results showed that the number of a patient's previous visits with their oncologist was significantly associated with a longer duration of HRQOL talk during their audio-recorded clinic visit. The remaining independent variables, gender concordance, race concordance, patient education status, and patient marital status were not significant predictors of duration of HRQOL talk. Conclusions: Our findings suggest that length of the patient-oncologist relationship is related to duration of HRQOL talk. Improvements in HRQOL communication may best be achieved through efforts directed at those in earlier stages of the doctor-patient relationship. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Rodriguez, Keri L.; Bayliss, Nichole K.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Rodriguez, Keri L.; Arnold, Robert M.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Rodriguez, Keri L.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15206 USA. [Bayliss, Nichole K.] Univ Pittsburgh, Dept Sociol, Pittsburgh, PA USA. [Alexander, Stewart C.; Jeffreys, Amy S.; Olsen, Maren K.; Tulsky, James A.] Durham VA Med Ctr, Durham, NC USA. [Alexander, Stewart C.; Tulsky, James A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Alexander, Stewart C.; Garrigues, Sarah K.; Tulsky, James A.] Duke Univ, Med Ctr, Ctr Palliat Care, Durham, NC USA. [Olsen, Maren K.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [Pollak, Kathryn I.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Pollak, Kathryn I.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Duke Canc Prevent Detect & Control Res Program, Durham, NC 27710 USA. [Tulsky, James A.] Duke Univ, Med Ctr, Ctr Aging & Human Dev, Durham, NC USA. [Arnold, Robert M.] Univ Pittsburgh, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. [Arnold, Robert M.] Univ Pittsburgh, Inst Enhance Palliat Care, Pittsburgh, PA USA. RP Rodriguez, KL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,Bldg 2,Rm 4083E 151C-H, Pittsburgh, PA 15206 USA. EM Keri.rodriguez@va.gov FU VA HSRD [MRP 04-410]; National Cancer Institute [3R01 CA-100387-03S1, R01CA100387]; Department of Veterans Affairs [RCD 07-006] FX Dr Rodriguez is supported by a VA HSR&D Merit Review Entry Program Award (MRP 04-410) and a Minority Supplement Award from the National Cancer Institute (3R01 CA-100387-03S1). Dr Alexander is supported by Health Services Research Career Development Award RCD 07-006 from the Department of Veterans Affairs. This work was supported in part by a grant awarded to Dr Tulsky by the National Cancer Institute (R01CA100387). NR 40 TC 3 Z9 3 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD SEP PY 2011 VL 20 IS 9 BP 935 EP 942 DI 10.1002/pon.1829 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 823LB UT WOS:000295122700004 PM 20737643 ER PT J AU Bernardy, NC Hamblen, JL Friedman, MJ Ruzek, JI McFall, ME AF Bernardy, Nancy C. Hamblen, Jessica L. Friedman, Matthew J. Ruzek, Josef I. McFall, Miles E. TI Implementation of a Posttraumatic Stress Disorder Mentoring Program to Improve Treatment Services SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress disorder; mentoring; implementation; best management practice AB Three years ago the Department of Veterans Affairs (VA) charged the National Center for PTSD (NCPTSD) to develop a mentoring program to train directors of specialized PTSD clinical programs in effective management skills. There were three reasons for this. First, the number of veterans from the Afghanistan and Iraq conflicts coming to the VA for PTSD treatment was rapidly increasing. Second, a major augmentation in mental health staffing had brought many new clinicians to the VA who were unfamiliar with war-zone-related PTSD and with the VA system of care at a time of changing administrative requirements. Third, the clinical complexity of these veterans required additional mentoring because their PTSD was often associated with depression, mild traumatic brain injury, substance use, chronic pain, aggressive behavior, and/or insomnia. The resulting PTSD Mentoring Program created a national network of program directors to disseminate and implement best management practices by supporting local experts in their mentoring of other VA PTSD program directors. This article describes the implementation of the PTSD Mentoring Program and examines methods of how other programs can successfully use and adapt the mentoring model. A description of what is working and where obstacles still exist for the program is provided. Our experience with the program supports the use of peer mentoring as a method to offer educational training on trauma in different settings and using different modalities. C1 [Bernardy, Nancy C.; Hamblen, Jessica L.; Friedman, Matthew J.] Dartmouth Med Sch, Dept Psychiat, Dartmouth, NS, Canada. [Ruzek, Josef I.] VA Palo Alto Healthcare Syst, Natl Ctr PTSD, Palo Alto, CA USA. [Ruzek, Josef I.] Stanford Univ, Stanford, CA 94305 USA. [McFall, Miles E.] VA Puget Sound Healthcare Syst, Seattle, WA USA. [McFall, Miles E.] Univ Washington, Dept Psychiat, Sch Med, Seattle, WA 98195 USA. [Bernardy, Nancy C.; Hamblen, Jessica L.; Friedman, Matthew J.] White River Junct VAMC, Natl Ctr PTSD, White River Jct, VT USA. [Ruzek, Josef I.] Pacific Grad Sch Psychol, Palo Alto, CA USA. RP Bernardy, NC (reprint author), White River Junct VA Med Ctr, Natl Ctr PTSD 116D, 215 N Main St, White River Jct, VT 05001 USA. EM nancy.bernardy@va.gov NR 9 TC 6 Z9 6 U1 0 U2 1 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD SEP PY 2011 VL 3 IS 3 SI SI BP 292 EP 299 DI 10.1037/a0024847 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 823GF UT WOS:000295109800012 ER PT J AU Stolzmann, P Subramanian, S Abdelbaky, A Maurovich-Horvat, P Scheffel, H Tawakol, A Hoffmann, U AF Stolzmann, Paul Subramanian, Sharath Abdelbaky, Amr Maurovich-Horvat, Pal Scheffel, Hans Tawakol, Ahmed Hoffmann, Udo TI Complementary Value of Cardiac FDG PET and CT for the Characterization of Atherosclerotic Disease SO RADIOGRAPHICS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CORONARY-ARTERY-DISEASE; MULTISLICE COMPUTED-TOMOGRAPHY; CRITERIA WORKING GROUP; INTRAVASCULAR-ULTRASOUND; PLAQUE INFLAMMATION; PROGNOSTIC VALUE; HIGH-FAT; APPROPRIATENESS CRITERIA; DIAGNOSTIC PERFORMANCE AB For decades, the identification of significant luminal narrowing has been the hallmark to characterize the presence and extent of coronary artery disease. However, it is now known that characterizations of systemic atherosclerosis burden and inflammation, as well as the local quality of plaque composition and morphology, allow better characterization of coronary artery disease and thus may allow improved prediction of adverse cardiovascular events. Plaque characterized histologically as a thin-cap fibroatheroma (ie, an atheroma with a thin fibrous cap, an underlying lipid-rich necrotic core, and inflammatory activity) has been recognized as representing vulnerable or high-risk plaque. Positron emission tomography (PET) and cardiac computed tomography (CT) are noninvasive modalities that provide metabolic (PET) and morphologic (CT) information about atherosclerotic plaque. PET allows the quantification of the uptake of fluorine 18 fluorodeoxyglucose (FDG) within the arterial wall, which provides a measure of macrophage activity within atheromatous plaque. Coronary CT allows the depiction of plaque morphology and composition. Thus, integrated imaging with PET and CT (PET/CT) permits coregistration of FDG activity with the presence and morphology of plaque and may lead to improved characterization of vulnerable plaque or vulnerable patients, or both. This review details the methods and principles of cardiac FDG PET and coronary CT and provides an overview of the research, with an emphasis on the identification and characterization of vulnerable plaque. C1 [Stolzmann, Paul; Subramanian, Sharath; Abdelbaky, Amr; Maurovich-Horvat, Pal; Scheffel, Hans; Tawakol, Ahmed; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Stolzmann, Paul; Subramanian, Sharath; Abdelbaky, Amr; Maurovich-Horvat, Pal; Scheffel, Hans; Tawakol, Ahmed; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Stolzmann, Paul] Univ Zurich Hosp, Inst Diagnost & Intervent Radiol, CH-8091 Zurich, Switzerland. RP Stolzmann, P (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM paul.stolzmann@usz.ch OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU Swiss Society of Radiology FX A.T.: Related financial activities: none. Other financial activities: patents for methods and devices for detection and therapy of atheromatous plaque. H.S.: Related financial activities: grant from Swiss Society of Radiology. Other financial activities: none. NR 82 TC 9 Z9 9 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2011 VL 31 IS 5 BP 1255 EP 1269 DI 10.1148/rg.315115028 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 823KS UT WOS:000295121700006 PM 21918043 ER PT J AU Jin, G Bausch, D Knightly, T Liu, ZC Li, YQ Liu, BL Lu, J Chong, W Velmahos, GC Alam, HB AF Jin, Guang Bausch, Dirk Knightly, Thomas Liu, Zhengcai Li, Yongqing Liu, Baoling Lu, Jennifer Chong, Wei Velmahos, George C. Alam, Hasan B. TI Histone deacetylase inhibitors enhance endothelial cell sprouting angiogenesis in vitro SO SURGERY LA English DT Article; Proceedings Paper CT 6th Annual Academic Surgical Congress CY FEB 01-03, 2011 CL Huntington Beach, CA SP Assoc Acad Surg (AAS), Soc Univ Surg (SUS) ID GENE-EXPRESSION; GROWTH; HISTONE-DEACETYLASE-7; ACTIVATION; APOPTOSIS; MIGRATION; THERAPY; TARGET; CANCER AB Background. Treatment with histone deacetylases inhibitors (HDACi) such as valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) has been shown to improve survival after lethal insults through mechanisms that are incompletely understood. Cell survival under adverse conditions requires a. healthy network of capillaries to ensure adequate oxygen delivery. Angiogenic activation of endothelial cells to migrate and form sprouts is associated with characteristic changes in gene expression profiles. Because HDACi can modulate expression of various genes involved in angiogenic activity, we investigated the effect of these agents on capillary-like sprout formation in this study. Methods. Human umbilical vein endothelial cells (HUVECs) were cultured as multicellular spheroids within a type I collagen matrix, which promotes formation of sprouts resembling angiogenesis in vitro. HUVECs were cultured as multicellular spheroids within a type I collagen matrix, which promotes formation of sprouts (in vitro angiogenesis). Cells were cultured under the following conditions: Control (no growth factors); VPA (1 mmol/L); vascular endothelial growth factor (VEGF; 10 ng/mL); VPA + VEGF; SAHA (5 mmol/L), and SAHA + VEGF. After 24 hours of treatment, the length of spheroid sprouting and cell migration was assessed quantitatively. The levels of acetylated histone H3, phosphor-extracellular signal-regulated kinase (ERK)1/2, and beta-catenin in HUVECs were measured by Western blotting at 6 hours after treatment. Results. High levels of acetylated histone H3 were detected in VPA and SAHA treated-groups. Compared with the VEGF-alone treated group (2379 +/- 147.1 mu m), the spheroid sprouting was 1.7 times increased with VPA and VEGF combined treatment (3996 +/- 192.5 mu m; P < .01). Cell migrations did not show a significant difference after addition of VPA, whereas SAHA suppressed migration. Expression of beta-catenin was significantly increased by VPA and SAHA treatments. Addition of VPA greatly enhanced expression of phosphor-ERK1/2. Conclusion. Exposure of HUVECs to VPA and SAHA increased the expression of beta-catenin and enhanced spheroid sprout formation in vitro. Modulation of HDAC-dependent pathways may offer a novel approach to alter angiogenic processes and provide a useful therapeutic target. (Surgery 2011;150:429-35.) C1 [Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA 02114 USA. [Bausch, Dirk] Univ Freiburg Klinikum, Abt Allgemein & Viszeralchirurg, Freiburg, Germany. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org FU NIGMS NIH HHS [R01 GM084127, R01 GM084127-01A1, R01 GM084127-02, R01 GM084127-03, R01 GM084127-04] NR 27 TC 16 Z9 17 U1 0 U2 4 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 SEP PY 2011 VL 150 IS 3 BP 429 EP 435 DI 10.1016/j.surg.2011.07.001 PG 7 WC Surgery SC Surgery GA 823FQ UT WOS:000295108300008 PM 21878227 ER PT J AU Li, YQ Liu, BL Fukudome, EY Lu, J Chong, W Jin, G Liu, ZC Vehnahos, GC Demoya, M King, DR Alam, HB AF Li, Yongqing Liu, Baoling Fukudome, Eugene Y. Lu, Jenifer Chong, Wei Jin, Guang Liu, Zhengcai Vehnahos, George C. Demoya, Marc King, David R. Alam, Hasan B. TI Identification of citrullinated histone H3 as a potential serum protein biomarker in a lethal model of lipopolysaccharide-induced shock SO SURGERY LA English DT Article; Proceedings Paper CT 6th Annual Academic Surgical Congress CY FEB 01-03, 2011 CL Huntington Beach, CA SP Assoc Acad Surg (AAS), Soc Univ Surg (SUS) ID NEUTROPHIL EXTRACELLULAR TRAPS; PEPTIDYLARGININE DEIMINASE; SEPTIC SHOCK; SEPSIS; MEDIATORS; DISEASE; DEATH; BLOOD; ACID AB Background. Circulating proteins may serve as biomarkers for the early diagnosis and treatment of shock. We have recently demonstrated that treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, significantly improves survival in a rodent model of lipopolysaccharide (LPS)-induced septic shock. Preliminary proteomic data showed that LPS-induced shock altered a number of proteins in circulation, including histone H3 (H3) and citrullinated histone H3 (Cit H3). The present study was designed to confirm these findings and to test whether the pro-survival phenotype could be detected by an early alteration in serum biomarkers. Methods. Three experiments were performed. In experiment I, Western blotting was performed on serum samples from male C57B1/6J mice (n = 9, 3/group) that belonged to the following groups: (a) LPS (20 mg/kg)-induced septic shock, (b) SARA-treated septic shock, and (c) sham (no LPS, no SAHA). In experiment II, HL-60 granulocytes were cultured and treated with LPS (100 ng/m1) in the absence or presence of SAHA (10 mu mol/L). Sham (no LPS, no SAHA) granulocytes served as controls. The medium and cells were harvested at 3 hours, and proteins were measured with Western blots. In experiment III, a large dose (LD, 35 mg/kg) or small dose (SD, 10 mg/kg) of LPS was injected intraperitoneally into the C57B1/6J mice (n = 10 per group). Blood was collected at 3 hours, and serum proteins were determined by Western blots or enzyme-linked immunosorbent assay (ELISA). All of the Western blots were performed with antibodies against H3, Cit H3, and acetylated H3 (Ac H3). ELISA was performed with antibody against tumor necrosis factor (TNF)-alpha. Survival rates were recorded over 7 days. Results. In experiment I, intraperitoneal (IP) injection of LPS (20 mg/kg) significantly increased serum levels of H3, which was prevented by SAHA treatment. In experiment II, LPS (100 ng/mL) induced expression and secretion of Cit H3 and H3 proteins in neutrophilic HL-60 cells, which was decreased by SAHA treatment. In experiment III, administration of LPS (LD) caused a rise in serum H3 and Cit H3 but not Ac H3 at 3 hours, and all of these animals died within 23 hours (100% mortality). Decreasing the dose of LPS (SD) significantly reduced the mortality rate (10% mortality) as well as the circulating levels of Cit H3 (non detectable) and H3. An increase in serum TNF-alpha was found in both LPS (LD) and (SD) groups, but in a non-dose-dependent fashion. Conclusion. Our results reveal for the first time that Cit H3 is released into circulation during the early stages of LPS-induced shock. Moreover, serum levels of Cit H3 are significantly associated with severity of LPS-induced shock. Therefore, Cit H3 could serve as a potential protein biomarker for early diagnosis of septic shock, and for predicting its lethality. (Surgery 2011;150:442-51.) C1 [Li, Yongqing; Liu, Baoling; Fukudome, Eugene Y.; Lu, Jenifer; Chong, Wei; Jin, Guang; Liu, Zhengcai; Vehnahos, George C.; Demoya, Marc; King, David R.; Alam, Hasan B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, Boston, MA 02114 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,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org FU NIGMS NIH HHS [R01 GM084127-01A1, R01 GM084127, R01 GM084127-02, R01 GM084127-03, R01 GM084127-04] NR 22 TC 25 Z9 27 U1 3 U2 13 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 SEP PY 2011 VL 150 IS 3 BP 442 EP 451 DI 10.1016/j.surg.2011.07.003 PG 10 WC Surgery SC Surgery GA 823FQ UT WOS:000295108300010 PM 21878229 ER PT J AU Freedman, A AF Freedman, Arnold TI Follicular lymphoma: 2011 update on diagnosis and management SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; TERM-FOLLOW-UP; ANTI-CD20 MONOCLONAL-ANTIBODY; RANDOMIZED CONTROLLED-TRIAL; PROGRESSION-FREE SURVIVAL; PHASE-II TRIAL; INTERNATIONAL PROGNOSTIC INDEX; CHRONIC LYMPHOCYTIC-LEUKEMIA AB Disease overview: Follicular lymphoma (FL) is generally an indolent B-cell lymphoproliferative disorder of transformed follicular center B cells. FL is characterized by diffuse lymphoadenopathy, bone marrow involvement, splenomegaly, and less commonly other extranodal sites of involvement. In general, cytopenias can occur but constitutional symptoms of fever, nightsweats, and weight loss are uncommon. Diagnosis: Diagnosis is based on histology of preferably biopsy of a lymph node. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10 and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl-2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl-2 genes. Risk stratification: The Follicular Lymphoma International Prognostic Index prognostic model for FL uses five independent predictors of inferior survival: age >60 years, hemoglobin <12 g/dL, serum LDH > normal, Ann Arbor stage III/IV, number of involved nodal areas >4. The presence of 0-1, 2, and >= 3 adverse factors defines low, intermediate, and high-risk disease with median 10 year survivals in the pre-rituximab era of approximately 71, 51, and 36 months, respectively. With the use of more modern therapies, specifically anti-CD20 monoclonal antibody, the outcome has improved. Risk-adapted therapy: Observation continues to be adequate for asymptomatic patients with low bulk disease and no cytopenias. For patients needing therapy, most patients are treated with chemotherapy plus rituximab, which has improved response rates, duration of response, and overall survival. Randomized studies have shown additional benefit for maintenance rituximab both following chemotherapy-rituximab and single agent rituximab. Autologous stem cell transplantation has not shown a survival benefit in first remission patients. Stem cell transplantation (SCT) including both autologous and allogeneic SCT or experimental agent therapy is considered for recurrent disease. Am. J. Hematol. 86:769-775, 2011. (C) 2011 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Freedman, A (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. EM arnold_freedman@dfci.harvard.edu NR 109 TC 21 Z9 23 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD SEP PY 2011 VL 86 IS 9 BP 769 EP 775 DI 10.1002/ajh.22099 PG 7 WC Hematology SC Hematology GA 821VZ UT WOS:000295003800008 PM 21850659 ER PT J AU Sedaghat, AR Gallagher, TQ Sadow, PM Cunnane, ME Cunningham, MJ AF Sedaghat, Ahmad R. Gallagher, Thomas Q. Sadow, Peter M. Cunnane, Mary E. Cunningham, Michael J. TI Radiology Quiz Case 2: Pediatric base of tongue thyroglossal duct cyst (TGDC) SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID MALFORMATIONS; CHILDREN; NECK C1 [Sedaghat, Ahmad R.; Gallagher, Thomas Q.; Cunnane, Mary E.; Cunningham, Michael J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sedaghat, Ahmad R.; Gallagher, Thomas Q.; Sadow, Peter M.; Cunnane, Mary E.; Cunningham, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. RP Sedaghat, AR (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD SEP PY 2011 VL 137 IS 9 BP 955 EP 957 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 821VI UT WOS:000295002100016 PM 21930990 ER PT J AU Johnsen, AK Valdar, W Golden, L Ortiz-Lopez, A Hitzemann, R Flint, J Mathis, D Benoist, C AF Johnsen, Alyssa K. Valdar, William Golden, Louis Ortiz-Lopez, Adriana Hitzemann, Robert Flint, Jonathan Mathis, Diane Benoist, Christophe TI Genome-Wide and Species-Wide Dissection of the Genetics of Arthritis Severity in Heterogeneous Stock Mice SO ARTHRITIS AND RHEUMATISM LA English DT Article ID QUANTITATIVE TRAIT LOCI; RHEUMATOID-ARTHRITIS; COMPLEX TRAITS; EFFECTOR PHASE; ANIMAL-MODELS; DISEASE; ASSOCIATION; ANTIBODIES; ENZYME AB Objective. Susceptibility to inflammatory arthritis is determined by a complex set of environmental and genetic factors, but only a portion of the genetic effect can be explained. Conventional genome-wide screens of arthritis models using crosses between inbred mice have been hampered by the low resolution of results and by the restricted range of natural genetic variation sampled. The aim of this study was to address these limitations by performing a genome-wide screen for determinants of arthritis severity using a genetically heterogeneous cohort of mice. Methods. Heterogeneous stock (HS) mice derive from 8 founder inbred strains by serial intercrossing (n > 60), resulting in fine-grained genetic variation. With a cohort of 570 HS mice, we performed a genome-wide screen for determinants of arthritis severity in the K/BxN serum-transfer model. Results. We mapped regions on chromosomes 1, 2, 4, 6, 7, and 15 that contain quantitative trait loci influencing arthritis severity at a resolution of a few megabases. In several instances, these regions proved to contain 2 quantitative trait loci: the region on chromosome 2 included the C5 fraction of complement known to be required for K/BxN serum-transfer arthritis but also contained a second adjacent quantitative trait locus, for which an intriguing candidate is Ptgs1 (Cox1). Interesting candidates on chromosome 4 included the Padi family, encoding the peptidyl arginine deiminases responsible for citrulline protein modification; suggestively, Padi2 and Padi4 RNA expression was correlated with arthritis severity in HS mice. Conclusion. These results provide a broad overview of the genetic variation that controls the severity of K/BxN serum-transfer arthritis and suggest intriguing candidate genes for further study. C1 [Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Johnsen, Alyssa K.; Mathis, Diane; Benoist, Christophe] Brigham & Womens Hosp, Boston, MA 02115 USA. [Johnsen, Alyssa K.; Golden, Louis; Ortiz-Lopez, Adriana] Joslin Diabet Ctr, Boston, MA 02215 USA. [Valdar, William; Flint, Jonathan] Wellcome Trust Ctr Human Genet, Oxford, England. [Hitzemann, Robert] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur,NRB 1052, Boston, MA 02115 USA. EM dm@hms.harvard.edu; cbdm@hms.harvard.edu OI Flint, Jonathan/0000-0002-9427-4429 FU NIH (National Institute of Allergy and Infectious Diseases) [K08-AI0-72044-01A1]; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [R01-AR-055271]; Arthritis National Research Foundation FX Supported by the NIH (National Institute of Allergy and Infectious Diseases grant K08-AI0-72044-01A1 and National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R01-AR-055271 to Drs. Hitzemann, Flint, Mathis, and Benoist). Dr. Johnsen is recipient of an Arthritis National Research Foundation scholarship. NR 31 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 2011 VL 63 IS 9 BP 2630 EP 2640 DI 10.1002/art.30425 PG 11 WC Rheumatology SC Rheumatology GA 821WL UT WOS:000295005000012 PM 21560115 ER PT J AU Rascovsky, K Hodges, JR Knopman, D Mendez, MF Kramer, JH Neuhaus, J van Swieten, JC Seelaar, H Dopper, EGP Onyike, CU Hillis, AE Josephs, KA Boeve, BF Kertesz, A Seeley, WW Rankin, KP Johnson, JK Gorno-Tempini, ML Rosen, H Prioleau-Latham, CE Lee, A Kipps, CM Lillo, P Piguet, O Rohrer, JD Rossor, MN Warren, JD Fox, NC Galasko, D Salmon, DP Black, SE Mesulam, M Weintraub, S Dickerson, BC Diehl-Schmid, J Pasquier, F Deramecourt, V Lebert, F Pijnenburg, Y Chow, TW Manes, F Grafman, J Cappa, SF Freedman, M Grossman, M Miller, BL AF Rascovsky, Katya Hodges, John R. Knopman, David Mendez, Mario F. Kramer, Joel H. Neuhaus, John van Swieten, John C. Seelaar, Harro Dopper, Elise G. P. Onyike, Chiadi U. Hillis, Argye E. Josephs, Keith A. Boeve, Bradley F. Kertesz, Andrew Seeley, William W. Rankin, Katherine P. Johnson, Julene K. Gorno-Tempini, Maria-Luisa Rosen, Howard Prioleau-Latham, Caroline E. Lee, Albert Kipps, Christopher M. Lillo, Patricia Piguet, Olivier Rohrer, Jonathan D. Rossor, Martin N. Warren, Jason D. Fox, Nick C. Galasko, Douglas Salmon, David P. Black, Sandra E. Mesulam, Marsel Weintraub, Sandra Dickerson, Brad C. Diehl-Schmid, Janine Pasquier, Florence Deramecourt, Vincent Lebert, Florence Pijnenburg, Yolande Chow, Tiffany W. Manes, Facundo Grafman, Jordan Cappa, Stefano F. Freedman, Morris Grossman, Murray Miller, Bruce L. TI Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia SO BRAIN LA English DT Article DE behavioural variant frontotemporal dementia; diagnostic criteria; frontotemporal lobar degeneration; FTD; pathology ID CEREBRAL-BLOOD-FLOW; FRONTAL ASSESSMENT BATTERY; ALZHEIMERS-DISEASE; LOBAR DEGENERATION; SEMANTIC DEMENTIA; VASCULAR DEMENTIA; TEMPORAL VARIANTS; PICKS-DISEASE; NEURODEGENERATIVE DISEASE; NEUROPSYCHIATRIC SYMPTOMS AB Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, 'possible' behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). 'Probable' behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia 'with definite frontotemporal lobar degeneration' requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer's disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met 'possible' criteria, and 104 (76%) met criteria for 'probable' behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with 'possible' and 'probable' criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines. C1 [Rascovsky, Katya; Grossman, Murray] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Hodges, John R.; Lillo, Patricia; Piguet, Olivier] Neurosci Res Australia, Randwick, NSW 2031, Australia. [Hodges, John R.; Lillo, Patricia; Piguet, Olivier] Univ New S Wales, Randwick, NSW 2031, Australia. [Knopman, David; Josephs, Keith A.; Boeve, Bradley F.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Mendez, Mario F.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Kramer, Joel H.; Seeley, William W.; Rankin, Katherine P.; Gorno-Tempini, Maria-Luisa; Rosen, Howard; Prioleau-Latham, Caroline E.; Lee, Albert; Miller, Bruce L.] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Neuhaus, John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. [van Swieten, John C.; Seelaar, Harro; Dopper, Elise G. P.] Erasmus MC, Dept Neurol, NL-3015 CE Rotterdam, Netherlands. [Onyike, Chiadi U.] Johns Hopkins Univ, Sch Med, Div Neuropsychiat & Geriatr Psychiat, Baltimore, MD 21287 USA. [Hillis, Argye E.] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21287 USA. [Kertesz, Andrew] Univ Western Ontario, Dept Neurol, London, ON N6A 4V2, Canada. [Johnson, Julene K.] Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94143 USA. [Kipps, Christopher M.] Southampton Univ NHS Trust, Wessex Neurol Ctr, Southampton SO16 6YD, Hants, England. [Kipps, Christopher M.] Univ Southampton, Dept Clin Neurosci, Southampton SO16 6YD, Hants, England. [Rohrer, Jonathan D.; Rossor, Martin N.; Warren, Jason D.; Fox, Nick C.] UCL Inst Neurol, Dementia Res Ctr, London WC1N 3BG, England. [Galasko, Douglas; Salmon, David P.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Galasko, Douglas] Univ Calif San Diego, VA Med Ctr, San Diego, CA 92161 USA. [Black, Sandra E.] Univ Toronto, Dept Med Neurol, Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Mesulam, Marsel; Weintraub, Sandra] Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Chicago, IL 60611 USA. [Dickerson, Brad C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. [Dickerson, Brad C.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Diehl-Schmid, Janine] Tech Univ Muenchen, Dept Psychiat, D-81675 Munich, Germany. [Pasquier, Florence; Deramecourt, Vincent; Lebert, Florence] Univ Lille Nord France, Dept Neurol, F-59000 Lille, France. [Pasquier, Florence; Deramecourt, Vincent; Lebert, Florence] Univ Lille Nord France, Dept Histol, F-59000 Lille, France. [Pijnenburg, Yolande] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, NL-1007 MB Amsterdam, Netherlands. [Pijnenburg, Yolande] Vrije Univ Amsterdam Med Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands. [Chow, Tiffany W.; Freedman, Morris] Baycrest, Rotman Res Inst, Toronto, ON M6A 2E1, Canada. [Chow, Tiffany W.] Univ Toronto, Dept Med, Toronto, ON M6A 2E1, Canada. [Chow, Tiffany W.] Univ Toronto, Dept Psychiat, Toronto, ON M6A 2E1, Canada. [Manes, Facundo] Favaloro Univ, Inst Cognit Neurol, RA-1126 Buenos Aires, DF, Argentina. [Grafman, Jordan] Kessler Fdn, Traumat Brain Injury Res Lab, Res Ctr, W Orange, NJ 07052 USA. [Cappa, Stefano F.] Univ Vita Salute San Raffaele, Dept Psychol, I-20132 Milan, Italy. [Cappa, Stefano F.] Univ Vita Salute San Raffaele, Dept Neurosci, I-20132 Milan, Italy. [Freedman, Morris] Baycrest, Div Neurol, Dept Med, Toronto, ON M6A 2E1, Canada. RP Rascovsky, K (reprint author), Univ Penn, Perelman Sch Med, Dept Neurol, 3400 Spruce St,3 W Gates, Philadelphia, PA 19104 USA. EM katyaras@mail.med.upenn.edu RI Hodges, John/B-9907-2012; Lillo, Patricia/B-9730-2013; Piguet, Olivier/C-9658-2011; Gorno-Tempini, Maria Luisa/E-7203-2012; Fox, Nick/B-1319-2009; LICEND, CEMND/F-1296-2015; OI Piguet, Olivier/0000-0002-6696-1440; Fox, Nick/0000-0002-6660-657X; Black, Sandra/0000-0001-7093-8289; Grafman, Jordan H./0000-0001-8645-4457; Rohrer, Jonathan/0000-0002-6155-8417 FU National Institutes of Health [P01-AG17586, R01-NS44266, P01-AG32953, R01-AG15116, P50-AG016574, P01-AG019724, P50-AG023501, R01-AG034499-02]; Department of Health Services from the state of California [CA DHS 07-65807] FX National Institutes of Health (P01-AG17586, R01-NS44266, P01-AG32953, R01-AG15116, P50-AG016574, P01-AG019724, P50-AG023501, R01-AG034499-02); Department of Health Services grant from the state of California (CA DHS 07-65807). NR 172 TC 902 Z9 927 U1 20 U2 123 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2011 VL 134 BP 2456 EP 2477 DI 10.1093/brain/awr179 PN 9 PG 22 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 821FH UT WOS:000294959800007 PM 21810890 ER PT J AU Zeng, X Levine, RA Hua, LQ Morris, EL Kang, YJ Flaherty, M Morgan, NV Hung, J AF Zeng, Xin Levine, Robert A. Hua, Lanqi Morris, Eleanor L. Kang, Yuejian Flaherty, Mary Morgan, Nina V. Hung, Judy TI Diagnostic Value of Vena Contracta Area in the Quantification of Mitral Regurgitation Severity by Color Doppler 3D Echocardiography SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE mitral regurgitation; diagnosis; 3D echocardiography; Doppler echocardiography ID ISOVELOCITY SURFACE-AREA; TIME 3-DIMENSIONAL ECHOCARDIOGRAPHY; IN-VITRO VALIDATION; VOLUME FLOW-RATE; MYOCARDIAL-INFARCTION; HEART-FAILURE; CONVERGENCE; RECONSTRUCTION; REGION; SHAPE AB Background-Accurate quantification of mitral regurgitation (MR) is important for patient treatment and prognosis. Three-dimensional echocardiography allows for the direct measure of the regurgitant orifice area (ROA) by 3D-guided planimetry of the vena contracta area (VCA). We aimed to (1) establish 3D VCA ranges and cutoff values for MR grading, using the American Society of Echocardiography-recommended 2D integrative method as a reference, and (2) compare 2D and 3D methods of ROA to establish a common calibration for MR grading. Methods and Results-Eighty-three patients with at least mild MR underwent 2D and 3D echocardiography. Direct planimetry of VCA was performed by 3D echocardiography. Two-dimensional quantification of MR included 2D ROA by proximal isovelocity surface area (PISA) method, vena contracta width, and ratio of jet area to left atrial area. There were significant differences in 3D VCA among patients with different MR grades. As assessed by receiver operating characteristic analysis, 3D VCA at a best cutoff value of 0.41 cm(2) yielded 97% of sensitivity and 82% of specificity to differentiate moderate from severe MR. There was significant difference between 2D ROA and 3D VCA in patients with functional MR, resulting in an underestimation of ROA by 2D PISA method by 27% as compared with 3D VCA. Multivariable regression analysis showed functional MR as etiology was the only predictor of underestimation of ROA by the 2D PISA method. Conclusions-Three-dimensional VCA provides a single, directly visualized, and reliable measurement of ROA, which classifies MR severity comparable to current clinical practice using the American Society of Echocardiography-recommended 2D integrative method. The 3D VCA method improves accuracy of MR grading compared with the 2D PISA method by eliminating geometric and flow assumptions, allowing for uniform clinical grading cutoffs and ranges that apply regardless of etiology and orifice shape. (Circ Cardiovasc Imaging. 2011;4:506-513.) C1 [Zeng, Xin; Levine, Robert A.; Hua, Lanqi; Morris, Eleanor L.; Kang, Yuejian; Flaherty, Mary; Morgan, Nina V.; Hung, Judy] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org FU National Institutes of Health (NIH)/National Heart, Lung and Blood Institute (NHLBI) [R01 HL092101, R01 038176, K24 HL67434]; American Society of Echocardiography; Leducq Foundation, Paris, France [07CVD04] FX This work was supported in part by grant R01 HL092101 from National Institutes of Health (NIH)/National Heart, Lung and Blood Institute (NHLBI) and by Echo-Investigator Award from the American Society of Echocardiography (Dr Hung); and grants R01 038176 and K24 HL67434 from NIH/NHLBI and grant 07CVD04 from the Leducq Foundation, Paris, France (Dr Levine). NR 24 TC 44 Z9 48 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2011 VL 4 IS 5 BP 506 EP U91 DI 10.1161/CIRCIMAGING.110.961649 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 822FY UT WOS:000295030600009 PM 21730026 ER PT J AU Thibault, H Gomez, L Bergerot, C Augeul, L Scherrer-Crosbie, M Ovize, M Derumeaux, G AF Thibault, Helene Gomez, Ludovic Bergerot, Cyrille Augeul, Lionel Scherrer-Crosbie, Marielle Ovize, Michel Derumeaux, Genevieve TI Strain-Rate Imaging Predicts the Attenuation of Left Ventricular Remodeling Induced by Ischemic Postconditioning After Myocardial Infarction in Mice SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE cardioprotection; echocardiography; strain rate; murine model; ischemia/reperfusion ID MITOCHONDRIAL PERMEABILITY TRANSITION; SPECKLE-TRACKING ECHOCARDIOGRAPHY; LONGITUDINAL STRAIN; REPERFUSION THERAPY; SIZE; TRANSMURALITY; DYSFUNCTION; INHIBITION; VALIDATION; RECOVERY AB Background-Systolic strain rate (SR) has been shown to correlate with the transmural extent of myocardial infarction (MI). Ischemic postconditioning (PC) decreases MI size. We aimed to determine whether SR may predict the reduction of left ventricular (LV) remodeling induced by PC in a murine model of ischemia-reperfusion. Methods and Results-C57BL6 mice underwent 60 minutes of left coronary artery occlusion followed by reperfusion. PC consisted of 3 cycles of 1 minute of reperfusion and 1 minute of ischemia performed immediately after reperfusion. After 24 hours of reperfusion, a first subset of mice was euthanized for determination of infarct size. An additional subset of mice underwent 3 months of reperfusion. Echocardiography and SR were serially assessed at baseline, 3 days, and 1, 2, 3 months after reperfusion. PC decreased the infarct size and increased SR values within infarcted segments as soon as 24 hours after reperfusion as compared with controls (14 +/- 1 versus 6 +/- 1 s(-1), P < 0.001). Systolic SR was correlated with MI size assessed by the area of infarction/area at risk (r=-0.88, P < 0.001). At 3 months, PC improved LV ejection fraction (55 +/- 4 versus 45 +/- 3%; P < 0.05) and decreased LV dimensions as compared with controls. Strain rate at day 3 correlated with LV ejection fraction (0.75; P < 0.001), end-systolic (r=-0.75; P=0.001), and end-diastolic volumes (r=-0.70; P < 0.001) at month 3. Conclusions-In this murine model of MI, SR accurately assessed the reduction in MI size induced by PC early after reperfusion and the subsequent reduction of LV remodeling. (Circ Cardiovasc Imaging. 2011;4:550-557.) C1 [Thibault, Helene; Gomez, Ludovic; Augeul, Lionel; Scherrer-Crosbie, Marielle; Derumeaux, Genevieve] U1060 CARMEN, F-69373 Lyon, France. [Thibault, Helene; Gomez, Ludovic; Augeul, Lionel; Ovize, Michel; Derumeaux, Genevieve] Univ Lyon 1, F-69622 Villeurbanne, France. [Thibault, Helene; Bergerot, Cyrille; Ovize, Michel; Derumeaux, Genevieve] Hosp Civils Lyon, Hop Louis Pradel, Serv Explorat Fonct Cardiovasc, Lyon, France. [Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Derumeaux, G (reprint author), U1060 CARMEN, 8 Ave Rockefeller, F-69373 Lyon, France. EM genevieve.derumeaux@chu-lyon.fr FU Societe Francaise de Cardiologie/Federation Francaise de Cardiologie; General Electric FX Dr Thibault received a grant from the "Societe Francaise de Cardiologie/Federation Francaise de Cardiologie."; Dr Derumeaux received research support from General Electric, who loaned echocardiography equipment (Vivid 7, GE Medical Systems) to our laboratory for this study. NR 32 TC 6 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2011 VL 4 IS 5 BP 550 EP U144 DI 10.1161/CIRCIMAGING.110.962282 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 822FY UT WOS:000295030600014 PM 21737599 ER PT J AU Chatterjee, NA Lewis, GD AF Chatterjee, Neal A. Lewis, Gregory D. TI What Is the Prognostic Significance of Pulmonary Hypertension in Heart Failure? SO CIRCULATION-HEART FAILURE LA English DT Editorial Material DE Editorials; heart failure; hemodynamics; pulmonary hypertension ID PRESERVED EJECTION FRACTION; INHALED NITRIC-OXIDE; IDIOPATHIC DILATED CARDIOMYOPATHY; VENTRICULAR SYSTOLIC FUNCTION; NATRIURETIC PEPTIDE; EXERCISE CAPACITY; PHOSPHODIESTERASE-5 INHIBITION; ARTERY PRESSURE; DETERMINANTS; SILDENAFIL C1 [Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Sch Med,Div Cardiol,Dept Med, Boston, MA 02114 USA. RP Lewis, GD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Sch Med,Div Cardiol,Dept Med, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM glewis@partners.org FU NHLBI NIH HHS [K23HL091106, U01-HL084877, K23 HL091106] NR 40 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2011 VL 4 IS 5 BP 541 EP 545 DI 10.1161/CIRCHEARTFAILURE.111.963785 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 822HQ UT WOS:000295035000005 PM 21934090 ER PT J AU Krum, H Elsik, M Schneider, HG Ptaszynska, A Black, M Carson, PE Komajda, M Massie, BM McKelvie, RS McMurray, JJ Zile, MR Anand, IS AF Krum, Henry Elsik, Maros Schneider, Hans G. Ptaszynska, Agata Black, Marion Carson, Peter E. Komajda, Michel Massie, Barry M. McKelvie, Robert S. McMurray, John J. Zile, Michael R. Anand, Inder S. TI Relation of Peripheral Collagen Markers to Death and Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction Results of the I-PRESERVE Collagen Substudy SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure; diastolic pressure; ventricular ejection fraction; collagen; fibrosis; osteopontin ID MYOCARDIAL FIBROSIS; DIASTOLIC DYSFUNCTION; TERMINAL PROPEPTIDE; SYSTOLIC FUNCTION; TURNOVER; DISEASE; CARDIOMYOPATHY; PROCOLLAGEN; IRBESARTAN; INSIGHTS AB Background-Heart failure with preserved ejection fraction (HFPEF) is a common and increasing public health problem. Myocardial fibrosis is a key pathological feature of HFPEF. Peripheral collagen markers may reflect this excess fibrosis; however, the relation of these markers to prognosis in patients with HFPEF has not as yet been determined. Methods and Results-This substudy of the Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) trial measured plasma levels of procollagen type I amino-terminal peptide, procollagen type III amino-terminal peptide, and osteopontin in 334 patients with HFPEF. Measurements were performed at baseline and 6 months after randomization to placebo or irbesartan 300 mg/day. The relation of baseline collagen markers to the I-PRESERVE primary end point (all-cause death and hospitalization for prespecified cardiovascular causes) was evaluated by single and multivariable analysis. Similar evaluations were performed for all-cause death alone as well as heart failure events (death or hospitalization because of heart failure). Increased plasma levels of collagen markers at baseline were associated with increased frequency of the study primary end point for all collagen markers. For each 10-mu g/L increase in procollagen type I amino-terminal peptide, the hazard ratio (HR) for the primary end point was 1.09 (95% CI, 1.052 to 1.13; P<0.0001); for each 10-mu g/L increase in procollagen type III amino-terminal peptide procollagen type I amino-terminal peptide, the HR was 2.47 (95% CI, 0.97 to 6.33; P=0.059); and for each 10-nmol/L increase in osteopontin, the HR was 1.084 (95% CI, 1.026 to 1.15; P=0.004). No variable remained significant as an independent predictor when introduced into a multivariable model. Both treatment groups tended to reduce collagen markers, with the reduction significantly greater for placebo versus irbesartan for procollagen type III amino-terminal peptide only (P=0.0185). Conclusions-Increased peripheral collagen turnover markers were not independently associated with increased mortality and cardiovascular hospitalization in an HFPEF population on multivariable analysis but were associated on single-variable analysis. These findings provide some support to the hypothesis that pathological fibrosis in the heart, and possibly the peripheral vasculature, may be contributory to adverse clinical outcomes in patients with HFPEF. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.(Circ Heart Fail. 2011;4:561-568.) C1 [Krum, Henry; Elsik, Maros] Monash Univ, Alfred Hosp, Ctr Cardiovasc Res & Educ Therapeut, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Schneider, Hans G.; Black, Marion] Alfred Hosp, Dept Pathol, Melbourne, Vic, Australia. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. [Ptaszynska, Agata] Bristol Myers Squibb Co, Princeton, NJ USA. [Komajda, Michel] Univ Paris 06, Paris, France. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [McKelvie, Robert S.] McMaster Univ, Hamilton, ON, Canada. [McMurray, John J.] Univ Glasgow, Glasgow, Lanark, Scotland. [Zile, Michael R.] VA Med Ctr, RHJ Dept, Charleston, SC USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Anand, Inder S.] VA Med Ctr, Minneapolis, MN USA. [Anand, Inder S.] Univ Minnesota, Minneapolis, MN USA. RP Krum, H (reprint author), Monash Univ, Alfred Hosp, Ctr Cardiovasc Res & Educ Therapeut, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. EM henry.krum@monash.edu OI mcmurray, john/0000-0002-6317-3975 FU Bristol-Myers Squibb; Sanofi-Aventis; Janssen-Cilag; Abbott; Roche; Veterans Administration (VA) nonprofit foundation; Glasgow University FX This study was supported by Bristol-Myers Squibb and Sanofi-Aventis.; Dr Krum has received honoraria for being the I-PRESERVE Australia coordinator. Dr Schneider has received research grant support for NGAL in congestive heart failure, fatty acid-binding protein in brain injury, and high-sensitivity troponin in general medicine; received other research support from Janssen-Cilag for brain natriuretic peptide study; received expense payment only from Abbott and Roche; has served as an expert witness for troponin in diagnosis of acute myocardial infarction (legal case); and has served as an expert witness for Victorian Ombudsman. Dr Ptaszynska is an employee of Bristol-Myers Squibb, who sponsored data collection. Dr Michel Komajda has served on the speakers bureau for Servier, Menarini, Bristol-Meyers Squibb, AstraZeneca, GlaxoSmithKline, and Sanofi-Aventis and has received honoraria from Servier, Duke University, Nile Therapeutics, and Sanofi-Aventis. Dr Massie has received research grant support from a Veterans Administration (VA) nonprofit foundation and received payments to cover the costs for patients enrolled at the site, has received other research support from a VA research grant related to implantable cardioverter-defibrillator in the VA system, and has received consultant fees from Bristol-Meyers Squibb for time spent as principal investigator of the trial. Dr McKelvie has received honoraria from Bristol-Meyers Squibb. Dr McMurray has received research support from Glasgow University for participation as co-principal investigator in a clinical trial program that included a study in HFPEF. Dr Zile serves as a member of the Executive Committee and chairman of the EndPoints Committee. Dr Anand has received research grant support as principal investigator on I-Preserve and honoraria as a member of the EndPoint Committee. Drs Krum, Carson, Komajda, Massie, McKelvie, McMurrray, Zile, and Anand are members of the I-PRESERVE Steering Committee and have received honoraria and travel support from Bristol-Myers Squibb to attend Steering Committee meetings. NR 19 TC 35 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2011 VL 4 IS 5 BP 561 EP 568 DI 10.1161/CIRCHEARTFAILURE.110.960716 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 822HQ UT WOS:000295035000008 PM 21750125 ER PT J AU Anand, IS Rector, TS Cleland, JG Kuskowski, M McKelvie, RS Persson, H McMurray, JJ Zile, MR Komajda, M Massie, BM Carson, PE AF Anand, Inder S. Rector, Thomas S. Cleland, John G. Kuskowski, Michael McKelvie, Robert S. Persson, Hans McMurray, John J. Zile, Michael R. Komajda, Michel Massie, Barry M. Carson, Peter E. TI Prognostic Value of Baseline Plasma Amino-Terminal Pro-Brain Natriuretic Peptide and Its Interactions With Irbesartan Treatment Effects in Patients With Heart Failure and Preserved Ejection Fraction Findings From the I-PRESERVE Trial SO CIRCULATION-HEART FAILURE LA English DT Article DE heart failure, diastolic; ventricular ejection fraction; pro-brain natriuretic peptide (1-76); pathophysiology; prognosis; biological markers ID DIASTOLIC DYSFUNCTION; PREDICTION; CARVEDILOL; MORTALITY; ALISKIREN; OUTCOMES; CORONA; HEFT AB Background-Plasma concentrations of natriuretic peptides (NPs) are associated with morbidity and mortality in patients with systolic heart failure (HF). However, the role of NP as a prognostic marker in patients with HF and preserved ejection fraction (HFpEF) has not been studied in a large cohort of well-characterized patients. Moreover, it is unclear whether treatments have a differential effect on morbidity and mortality across the spectrum of NP levels. Methods and Results-N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured at baseline in 3480 patients in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Trial). In a multivariable Cox regression model, NT-proBNP above the median of 339 pg/mL was independently associated with an increased risk of the primary end point of all-cause mortality and prespecified cardiovascular hospitalizations (adjusted hazard ratio [HR], 1.79; 95% CI, 1.56 to 2.10; P<0.001); all-cause mortality (adjusted HR, 2.04; 95% CI, 1.68 to 2.47; P<0.001); and a composite of HF events, including death due to worsening HF or sudden death or hospitalization due to worsening HF (adjusted HR, 1.77; 95% CI, 1.43 to 2.20; P<0.001). There were significant interactions between the effect of irbesartan and median split of baseline NT-proBNP for the primary outcome (P=0.005), all-cause mortality (P=0.05), and the HF composite outcome (P<0.001). Use of irbesartan was associated with improved outcomes in patients with NT-proBNP below, but not above, the median. After adjusting for 20 baseline covariates, irbesartan still had a beneficial effect on the primary outcome (HR, 0.74; 95% CI, 0.60 to 90; P=0.003), all-cause mortality (HR, 0.75; 95% CI, 0.56 to 0.99; P=0.046), and HF composite outcome (HR, 0.57; 95% CI, 0.41 to 0.80; P=0.001) in patients with NT-proBNP below the median. Conclusions-The unexpected benefit of irbesartan in lower-risk patients with HFpEF in this post hoc analysis may indicate effects on early, but not later, high-risk stages of the disease. These findings question the strategy of using elevated plasma concentrations of NP as a patient selection criterion in HFpEF trials. More studies are needed to support or contest this practice. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238. (Circ Heart Fail. 2011;4:569-577.) C1 [Anand, Inder S.; Rector, Thomas S.; Kuskowski, Michael] VA Med Ctr, Minneapolis, MN 55417 USA. [Anand, Inder S.; Rector, Thomas S.; Kuskowski, Michael] Univ Minnesota, Minneapolis, MN USA. [Cleland, John G.] Univ Hull, Castle Hill Hosp, Dept Cardiol, Kingston Upon Hull, Yorks, England. [McKelvie, Robert S.] Populat Hlth Res Inst, Hamilton, ON, Canada. [McKelvie, Robert S.] McMaster Univ, Hamilton, ON, Canada. [Persson, Hans] Danderyd Hosp, Dept Clin Sci, Karolinska Inst, Stockholm, Sweden. [McMurray, John J.] British Heart Fdn Glasgow, Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Zile, Michael R.] Vet Affairs Med Ctr, RHJ Dept, Charleston, SC 29403 USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Komajda, Michel] Univ Paris 06, Pitie Salpetriere Hosp, Paris, France. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Carson, Peter E.] Washington Vet Affairs Med Ctr, Washington, DC USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. RP Anand, IS (reprint author), VA Med Ctr, Cardiol 111-C,1 Vet Dr, Minneapolis, MN 55417 USA. EM anand001@umn.edu OI Cleland, John/0000-0002-1471-7016; mcmurray, john/0000-0002-6317-3975 FU Veterans Health Administration Health Services [HFP-98-001]; Center for Epidemiology and Clinical Research at the Minneapolis VA Medical Center FX Dr Rector was supported by Veterans Health Administration Health Services Research & Development Grant HFP-98-001and the Center for Epidemiology and Clinical Research at the Minneapolis VA Medical Center. The views expressed herein do not necessarily represent the views of the Department of Veterans Affairs. NR 25 TC 62 Z9 63 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD SEP PY 2011 VL 4 IS 5 BP 569 EP 577 DI 10.1161/CIRCHEARTFAILURE.111.962654 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 822HQ UT WOS:000295035000009 PM 21715583 ER PT J AU Wrobel, JS Reiber, GE AF Wrobel, James S. Reiber, Gayle E. TI Time for a Victory Lap or Time to Raise the Levees: A Perspective on Complication Reduction and New-Onset Diabetes SO DIABETES CARE LA English DT Editorial Material ID 10-YEAR FOLLOW-UP; PREVENTION PROGRAM; OUTCOMES; TRENDS; INTERVENTIONS; AMPUTATION; THERAPY C1 [Wrobel, James S.] Univ Michigan, Sch Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. [Reiber, Gayle E.] VA Puget Sound, Hlth Serv Res & Dev, Rehabil Res & Dev, Seattle, WA USA. [Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Wrobel, JS (reprint author), Univ Michigan, Sch Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. EM jswrobel@med.umich.edu NR 21 TC 0 Z9 0 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2011 VL 34 IS 9 BP 2130 EP 2132 DI 10.2337/dc11-1069 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 824IH UT WOS:000295195100042 PM 21868782 ER PT J AU Maa, EH Kahle, KT Walcott, BP Spitz, MC Staley, KJ AF Maa, Edward H. Kahle, Kristopher T. Walcott, Brian P. Spitz, Mark C. Staley, Kevin J. TI Diuretics and epilepsy: Will the past and present meet? SO EPILEPSIA LA English DT Article DE NKCC1; KCC2; Cation chloride cotransporter; Bumetanide; Mesial temporal sclerosis; Neonatal seizures ID K-CL COTRANSPORTER; TEMPORAL-LOBE EPILEPSY; CATION-CHLORIDE COTRANSPORTERS; HIPPOCAMPAL PYRAMIDAL CELLS; CONGESTIVE HEART-FAILURE; NEONATAL SEIZURES; IN-VITRO; EPILEPTIFORM ACTIVITY; EXTRACELLULAR-SPACE; REFRACTORY EPILEPSY AB Clinical studies from over half a century ago suggested efficacy of a variety of diuretics in focal and generalized epilepsies as well as in status epilepticus, but these findings have not been translated into modern epilepsy training or practice. Recent advances in our understanding of neuronal maturation and the pathophysiology of neonatal seizures provide fresh insight into the mechanisms by which diuretics might reduce susceptibility to seizures. In vitro and in vivo rodent studies and human epilepsy surgical cases have shown that specific diuretic agents targeting the cation-chloride cotransporters decrease neuronal synchrony and neuronal hyperexcitability. These agents are thought to convey their antiepileptic activity by either expanding the extracellular space or promoting a cellular chloride transport balance that reflects a more developmentally "mature," less excitable state. It may be time to reexamine whether diuretics could serve as adjunctive therapies in the treatment of refractory epilepsies. C1 [Maa, Edward H.] Denver Hlth & Hosp, Div Neurol, Denver, CO USA. [Maa, Edward H.; Spitz, Mark C.] Denver Vet Affairs Med Ctr, Dept Neurol, Denver, CO USA. [Maa, Edward H.; Spitz, Mark C.] Univ Colorado Denver, Hlth Sci Ctr, Dept Neurol, Denver, CO USA. [Kahle, Kristopher T.; Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA. RP Maa, EH (reprint author), 777 Bannock St,Mail Code 4000, Denver, CO 80204 USA. EM edward.maa@dhha.org NR 84 TC 17 Z9 17 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2011 VL 52 IS 9 BP 1559 EP 1569 DI 10.1111/j.1528-1167.2011.03203.x PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 821KK UT WOS:000294973700009 PM 21838793 ER PT J AU Timpano, KR Keough, ME Traeger, L Schmidt, NB AF Timpano, Kiara R. Keough, Meghan E. Traeger, Lara Schmidt, Norman B. TI General Life Stress and Hoarding: Examining the Role of Emotional Tolerance SO INTERNATIONAL JOURNAL OF COGNITIVE THERAPY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; SOCIAL-INTERACTION ANXIETY; DISTRESS TOLERANCE; PERSONALITY-DISORDER; PANIC-ATTACKS; PSYCHOMETRIC PROPERTIES; ABSTINENCE ATTEMPT; FUTURE-DIRECTIONS; SENSITIVITY; DEPRESSION AB Traumatic life events are one potential risk factor for hoarding, though little is known about mechanisms that could account for the association and it is unclear whether the relationship is unique to traumatic stressors. The present investigation examined the association between hoarding symptoms and general stress in a large nonclinical sample (N = 465). We also considered a model by which stress could be linked with hoarding. Results revealed that stress particularly interpersonal stress was related to greater hoarding symptoms, despite controlling for a range of mood and anxiety symptoms. Of the three cardinal hoarding domains, only clutter and acquiring had a robust association with stress. Path analysis found support for emotional intolerance as a partial mediator of the connection between stress and hoarding; however, the causal directionality of this model remains unclear. Results are discussed with respect to future investigations and the clinical implications of the connection between stress and hoarding. C1 [Timpano, Kiara R.] Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. [Keough, Meghan E.; Schmidt, Norman B.] Florida State Univ, Tallahassee, FL 32306 USA. [Traeger, Lara] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Traeger, Lara] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Timpano, KR (reprint author), Univ Miami, Dept Psychol, 5665 Ponce de Leon Blvd, Coral Gables, FL 33146 USA. EM kiaratim-pano@gmail.com RI Timpano, Kiara/C-8760-2012; OI Timpano, Kiara/0000-0002-0665-8722 NR 79 TC 14 Z9 14 U1 4 U2 8 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1937-1209 J9 INT J COGN THER JI Int. J. Cogn. Ther. PD SEP PY 2011 VL 4 IS 3 BP 263 EP 279 PG 17 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 822BN UT WOS:000295018800005 ER PT J AU Vu, TH Guha-Thakurta, N Harrell, RK Ahmed, S Kumar, AJ Johnson, VE Perrier, ND Hamberg, LM Hunter, GJ Schellingerhout, D AF Vu, Thinh H. Guha-Thakurta, Nandita Harrell, Robyn K. Ahmed, Salmaan Kumar, Ashok J. Johnson, Valen E. Perrier, Nancy D. Hamberg, Leena M. Hunter, George J. Schellingerhout, Dawid TI Imaging Characteristics of Hyperfunctioning Parathyroid Adenomas Using Multiphase Multidectector Computed Tomography: A Quantitative and Qualitative Approach SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE parathyroid adenoma localization; multiphase multidetector computed tomography; 4DCT ID GUIDE FOCUSED EXPLORATION; PRIMARY HYPERPARATHYROIDISM; DIRECTED PARATHYROIDECTOMY; PREOPERATIVE LOCALIZATION; SURGICAL-TREATMENT; SELECT PATIENTS; SCINTIGRAPHY; SPECT/CT AB Objective: The objective of the study was to characterize the enhancement pattern of hyperfunctioning parathyroid adenomas on multiphase multidetector computed tomography (CT) or 4-dimensional CT. Methods: We retrospectively studied the enhancement patterns of 48 pathologically confirmed parathyroid adenomas with 4-dimensional CT, compliant with institutional review and the Health Insurance Portability and Accountability Act. Region-of-interest analysis was done at baseline and at arterial (25 seconds), venous (55 seconds), and delayed (85 seconds) enhancement phases over the adenoma and adjacent normal thyroid tissue. Qualitative and quantitative analysis was done. Discriminant functions were calculated using a multivariate logistic regression model, and receiver operating characteristic curves were measured. Results: Adenomas are lower than thyroid in density, demonstrate avid early contrast enhancement, and show rapid wash-out of contrast. Adenomas and thyroid had baseline Hounsfield unit attenuations of 35 +/- 11 and 94 +/- 21 and enhancement percentage change from baseline to arterial of 493% +/- 328% and 132% +/- 148%, respectively (P < 0.0001 both). Quantitative analysis showed that these 2 measures of baseline density and the percentage change from baseline to arterial were the most powerful discriminatory features, with contrast wash-out from arterial peak to venous phase being a less powerful discriminator. Several discriminant functions were derived, the best of which was: X = 13.74 - (0.207 x baseline Hounsfield unit) - (0.006 x percent density change from baseline to arterial). X > 0.2 classifies tissue as parathyroid with high certainty (area under the receiver operating characteristic curve = 0.98; specificity, 0.938; sensitivity, 0.999). Conclusions: Parathyroid adenomas have a characteristic enhancement pattern that can be distinguished from thyroid tissue: the key diagnostic discriminators are baseline density, percentage change in density from baseline to arterial enhancement, and percentage decrease in density from arterial to venous phases. C1 [Vu, Thinh H.; Guha-Thakurta, Nandita; Ahmed, Salmaan; Kumar, Ashok J.; Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Harrell, Robyn K.] US Oncol, The Woodlands, TX USA. [Johnson, Valen E.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Perrier, Nancy D.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Hamberg, Leena M.; Hunter, George J.] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA. [Schellingerhout, Dawid] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Schellingerhout, D (reprint author), 1400 Pressler St,Unit 1482, Houston, TX 77030 USA. EM Dawid.Schellingerhout@di.mdacc.tmc.edu FU NCI NIH HHS [P30 CA016672] NR 21 TC 9 Z9 9 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2011 VL 35 IS 5 BP 560 EP 567 DI 10.1097/RCT.0b013e31822a1e70 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 821SH UT WOS:000294994200008 PM 21926850 ER PT J AU DeHaven, BC Gupta, K Isaacs, SN AF DeHaven, Brian C. Gupta, Kushol Isaacs, Stuart N. TI The vaccinia virus A56 protein: a multifunctional transmembrane glycoprotein that anchors two secreted viral proteins SO JOURNAL OF GENERAL VIROLOGY LA English DT Review ID COMPLEMENT-CONTROL PROTEIN; INTRACELLULAR MATURE VIRUS; ENTRY-FUSION COMPLEX; CELL-CELL-FUSION; INFECTED-CELLS; NUCLEOTIDE-SEQUENCE; HEMAGGLUTININ GENE; ECTROMELIA VIRUS; HUMAN MONKEYPOX; BALB/C MICE AB The vaccinia virus A56 protein was one of the earliest-described poxvirus proteins with an identifiable activity. While originally characterized as a haemagglutinin protein, A56 has other functions as well. The A56 protein is capable of binding two viral proteins, a serine protease inhibitor (K2) and the vaccinia virus complement control protein (VCP), and anchoring them to the surface of infected cells. This is important; while both proteins have biologically relevant functions at the cell surface, neither one can locate there on its own. The A56-K2 complex reduces the amount of virus superinfecting an infected cell and also prevents the formation of syncytia by infected cells; the A56-VCP complex can protect infected cells from complement attack. Deletion of the A56R gene results in varying effects on vaccinia virus virulence. In addition, since the gene encoding the A56 protein is non-essential, it can be used as an insertion point for foreign genes and has been deleted in some viruses that are in clinical development as oncolytic agents. C1 [DeHaven, Brian C.; Isaacs, Stuart N.] Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Gupta, Kushol] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. [Gupta, Kushol] Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. [Isaacs, Stuart N.] Philadelphia Vet Affairs Med Ctr, Infect Dis Sect, Philadelphia, PA 19104 USA. RP Isaacs, SN (reprint author), Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. EM isaacs@mail.med.upenn.edu FU Public Health Service, National Institute of Allergy and Infectious Disease [U01-AI077913, U01-AI066333, U54-AI057168]; [T32 AI07324] FX The authors would like to thank Joe Esposito for helpful discussions and the reviewers of the submitted manuscript whose comments helped improve this mini-review. S. N. I. is supported in part by Public Health Service grants U01-AI077913, U01-AI066333 and U54-AI057168 (Middle Atlantic Regional Center of Excellence in Biodefense and Emerging Infectious Diseases) from the National Institute of Allergy and Infectious Disease. B. C. D. is supported by institutional training grants T32 AI07324 and U01-AI066333. NR 86 TC 1 Z9 5 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 2011 VL 92 BP 1971 EP 1980 DI 10.1099/vir.0.030460-0 PN 9 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 822BO UT WOS:000295018900001 PM 21715594 ER PT J AU Beisele, M Shen, ZL Parry, N Mobley, M Taylor, NS Buckley, E Abedin, MZ Dewhirst, FE Fox, JG AF Beisele, Maike Shen, Zeli Parry, Nicola Mobley, Melissa Taylor, Nancy S. Buckley, Ellen Abedin, Mohammad Z. Dewhirst, Floyd E. Fox, James G. TI Helicobacter marmotae and novel Helicobacter and Campylobacter species isolated from the livers and intestines of prairie dogs SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID CHOLESTEROL GALLSTONE FORMATION; SP-NOV; HEPATICUS INFECTION; WILD RODENTS; MICE; GALLBLADDER; DISEASES; BILE; JEJUNI; CATS AB Prairie dogs (Cynomys ludovicianus) are used to study the aetiology and prevention of gallstones because of the similarities of prairie dog and human bile gallstone composition. Epidemiological and experimental studies have suggested a connection between infection with Helicobacter species and cholesterol cholelithiasis, cholecystis and gallbladder cancer. Ten of the 34 prairie dogs in this study had positive Helicobacter species identified by PCR using Helicobacter genus-specific primers. Ten of 34 prairie dogs had positive Campylobacter species identified in the intestine by PCR with Campylobacter genus-specific primers. Six Helicobacter sp. isolates and three Campylobacter sp. isolates were identified taxonomically by 16S rRNA gene analysis. The prairie dog helicobacters fell into three clusters adjacent to Helicobacter marmotae. On the basis of 16S rRNA gene sequence analysis, three strains in two adjacent clusters were included in the species H. marmotae. Three strains were only 97.1% similar to the sequence of H. marmotae and can be considered a novel species with the provisional designation Helicobacter sp. Prairie Dog 3. The prairie dog campylobacters formed a single novel cluster and represent a novel Campylobacter sp. with the provisional designation Campylobacter sp. Prairie Dog. They branched with Campylobacter cuniculorum at 96.3% similarity and had the greatest sequence similarity to Campylobacter helveticus at 97.1% similarity. Whether H. marmotae or the novel Helicobacter sp. and Campylobacter sp. identified in prairie dogs play a role in cholesterol gallstones or hepatobiliary disease requires further studies. C1 [Beisele, Maike; Shen, Zeli; Parry, Nicola; Mobley, Melissa; Taylor, Nancy S.; Buckley, Ellen; Fox, James G.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Dewhirst, Floyd E.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Abedin, Mohammad Z.] Drexel Univ, Coll Med, Philadelphia, PA 19102 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU National Institutes of Health [R01CA067529, R01DK052413, T32RR007036, P30ES002109, P01CA 026731, R01DK070865] FX This study was supported by National Institutes of Health grants R01CA067529, R01DK052413, T32RR007036, P30ES002109, P01CA 026731 (all to J. G. F.) and R01DK070865 (M. Z. A.). NR 46 TC 4 Z9 5 U1 2 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD SEP PY 2011 VL 60 IS 9 BP 1366 EP 1374 DI 10.1099/jmm.0.032144-0 PG 9 WC Microbiology SC Microbiology GA 822BM UT WOS:000295018700020 PM 21546560 ER PT J AU Wen, PY Schiff, D AF Wen, Patrick Y. Schiff, David TI Valproic acid as the AED of choice for patients with glioblastoma? The jury is out SO NEUROLOGY LA English DT Editorial Material ID AUTOPHAGY C1 [Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02215 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Schiff, David] Univ Virginia, Med Ctr, Charlottesville, VA USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, SW430D,450 Brookline Ave, Boston, MA 02215 USA. EM pwen@partners.org; ds4jd@virginia.edu NR 10 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 2011 VL 77 IS 12 BP 1114 EP 1115 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 822EX UT WOS:000295027800005 PM 21880995 ER PT J AU Bushnell, CD Olson, DM Zhao, X Pan, W Zimmer, LO Goldstein, LB Alberts, MJ Fagan, SC Fonarow, GC Johnston, SC Kidwell, C LaBresh, KA Ovbiagele, B Schwamm, L Peterson, ED AF Bushnell, C. D. Olson, D. M. Zhao, X. Pan, W. Zimmer, L. O. Goldstein, L. B. Alberts, M. J. Fagan, S. C. Fonarow, G. C. Johnston, S. C. Kidwell, C. LaBresh, K. A. Ovbiagele, B. Schwamm, L. Peterson, E. D. CA AVAIL Investigators TI Secondary preventive medication persistence and adherence 1 year after stroke SO NEUROLOGY LA English DT Article ID ISCHEMIC-STROKE; DRUG-THERAPY; PREDICTORS; REGISTRY; RISK AB Objective: Data on long-term use of secondary prevention medications following stroke are limited. The Adherence eValuation After Ischemic stroke-Longitudinal (AVAIL) Registry assessed patient, provider, and system-level factors influencing continuation of prevention medications for 1 year following stroke hospitalization discharge. Methods: Patients with ischemic stroke or TIA discharged from 106 hospitals participating in the American Heart Association Get With The Guidelines-Stroke program were surveyed to determine their use of warfarin, antiplatelet, antihypertensive, lipid-lowering, and diabetes medications from discharge to 12 months. Reasons for stopping medications were ascertained. Persistence was defined as continuation of all secondary preventive medications prescribed at hospital discharge, and adherence as continuation of prescribed medications except those stopped according to health care provider instructions. Results: Of the 2,880 patients enrolled in AVAIL, 88.4% (2,457 patients) completed 1-year interviews. Of these, 65.9% were regimen persistent and 86.6% were regimen adherent. Independent predictors of 1-year medication persistence included fewer medications prescribed at discharge, having an adequate income, having an appointment with a primary care provider, and greater understanding of why medications were prescribed and their side effects. Independent predictors of adherence were similar to those for persistence. Conclusions: Although up to one-third of stroke patients discontinued one or more secondary prevention medications within 1 year of hospital discharge, self-discontinuation of these medications is uncommon. Several potentially modifiable patient, provider, and system-level factors associated with persistence and adherence may be targets for future interventions. Neurology (R) 2011;77:1182-1190 C1 [Bushnell, C. D.] Wake Forest Sch Med, Dept Neurol, Winston Salem, NC 27157 USA. [Olson, D. M.; Zhao, X.; Pan, W.; Zimmer, L. O.; Peterson, E. D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Goldstein, L. B.] Duke Univ, Med Ctr, Dept Neurol, Durham, NC USA. [Alberts, M. J.] Northwestern Univ, Chicago, IL 60611 USA. [Fagan, S. C.] Univ Georgia, Augusta, GA USA. [Fonarow, G. C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Johnston, S. C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Kidwell, C.] Georgetown Univ, Dept Neurol, Washington, DC USA. [LaBresh, K. A.] Res Triangle Int, Res Triangle Pk, NC USA. [Ovbiagele, B.] Univ Calif Los Angeles, Sch Med, Stroke Ctr, Los Angeles, CA USA. [Ovbiagele, B.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA USA. [Schwamm, L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Bushnell, CD (reprint author), Wake Forest Sch Med, Dept Neurol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM cbushnel@wakehealth.edu RI LaBresh, Kenneth/A-6995-2017; OI LaBresh, Kenneth/0000-0001-9040-1956; Schwamm, Lee/0000-0003-0592-9145 FU Bristol-Myers Squibb/Sanofi; GWTG-Stroke program; Agency for Healthcare Research and Quality (AHRQ) [U18HS016964]; NIH/NINDS; American Heart Association/Bugher Foundation; Hazel K Goddess Fund for Research on Stroke in Women; AHRQ; holds stock in Abbott; Bayer Schering Pharma; Pfizer Inc; AGA Medical Corporation; Abbott; NIH; American Heart Association; El Centro Hispano; Athena Diagnostics, Inc. re; US Veterans Administration; sanofi-aventis; Strkyer Neurovascular; Boston Scientific; NIH (NCRR, NINDS); Kaiser-Permanente; AHA/ASA; Baxter International Inc.; Lundbeck Inc.; NIH (NINDS, NCRR); Department of Health and Human Services (CDC); Merck Serono FX Adherence eValuation After Ischemic stroke-Longitudinal (AVAIL) was supported by unrestricted funds from Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership and conducted through collaboration with the GWTG-Stroke program. AVAIL analyses were also supported in part by the Agency for Healthcare Research and Quality (AHRQ) cooperative agreement U18HS016964. DCRI developed the protocol, owns the data, and is responsible for study oversight, materials development and data collection, site communications, and all regulatory and clinical questions related to the AVAIL Registry study.; Dr. Bushnell serves on a data safety monitoring board for Boehringer Ingelheim; and received research support from the Bristol-Myers Squibb/Sanofi Partnership, the NIH/NINDS, the American Heart Association/Bugher Foundation, and the Hazel K Goddess Fund for Research on Stroke in Women. Dr. Olson serves on speakers' bureaus for and has received speaker honoraria from Zoll Medical, Integra Neuroscience, and The Medicines Company; and has received research support from the Bristol-Myers Squibb/Sanofi Partnership. X. Zhao and Dr. Pan report no disclosures. L. Zimmer receives research support from AHRQ and holds stock in Abbott. Dr. Goldstein serves on a scientific advisory board for Allergan; has received funding for travel and speaker honoraria from Bayer Schering Pharma; serves on the editorial boards of Neurology (R), Emergency Medicine, Stroke, Cerebrovascular Diseases, and Circulation: Cardiovascular Quality and Outcomes and as an Associate Editor for Continuum; receives publishing royalties from UpToDate and Henry Stewart Talks; serves as a consultant for Pfizer Inc, Boehringer Ingelheim, Johnson & Johnson, and Merck Serono; receives research support to his institution from Pfizer Inc, AGA Medical Corporation, and Abbott; and receives research support from the NIH, the American Heart Association, and El Centro Hispano. Dr. Alberts serves on a scientific advisory board, as a consultant, and on the speakers' bureau for and has received funding for travel and speaker honoraria from the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership; receives publishing royalties from Blackwell Publishing; and has received royalties from Athena Diagnostics, Inc. re: apoE genetic testing. Dr. Fagan serves on scientific advisory boards for Pfizer Inc and Genentech, Inc.; serves on the editorial board of Pharmacotherapy; serves as a consultant for Pfizer Inc, Genentech, Inc, and Ferrer Group; and receives research support from the NIH/NINDS and the US Veterans Administration. Dr. Fonarow serves as a consultant for Novartis and Pfizer Inc. Dr. Johnston is co-holder of patent re: the RNA panel to identify TIA and risk stratify; and receives research support from sanofi-aventis, Strkyer Neurovascular, Boston Scientific, the NIH (NCRR, NINDS), Kaiser-Permanente, and the AHA/ASA, Bugher Award. Dr. Kidwell serves on the editorial boards of Neurocritical Care, the Journal of Neuroimaging, and Stroke Research and Treatment; serves/served as a consultant for Embrella Cardiovascular, Inc., and Simcere Pharmaceutical Group; and receives research support from Baxter International Inc. and the NIH/NINDS. Dr. LaBresh reports no disclosures. Dr. Ovbiagele serves on a scientific advisory board for Avanir Pharmaceuticals and serves as an Assistant Editor of Stroke, an Associate Editor of Journal Watch Neurology and BMC Public Health, and on the editorial boards of the Journal of Stroke and Cerebrovascular Diseases and Stroke Research and Treatment. Dr. Schwamm serves as chair of the American Heart Association GWTG Steering Committee; serves on scientific advisory boards for CoAxia, Inc., Phreesia, and Lundbeck Inc.; serves on the editorial boards of Neurocritical Care and Stroke; may accrue revenue on a patent re: Imaging system for obtaining quantitative perfusion indices; his wife receives royalties from publishing Obstetric Anesthesia (Cambridge Pocket Clinicians, 2007); serves/has served as a consultant to CryoCath (R) Technologies Inc., Research Triangle Inc.; , Massachusetts Department of Public Health, and the Canadian Stroke Network; receives research supprt from Lundbeck Inc., the NIH (NINDS, NCRR), and the Department of Health and Human Services (CDC); and has provided expert medical opinions in malpractice lawsuits (re: stroke treatment and prevention). Dr. Peterson serves on the editorial board of the Journal of the American Medical Association and receives research support from Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership and Merck Serono. NR 21 TC 79 Z9 83 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 2011 VL 77 IS 12 BP 1182 EP 1190 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 822EX UT WOS:000295027800016 PM 21900638 ER PT J AU Hoen, PW de Jonge, P Na, BY Farzaneh-Far, R Epel, E Lin, J Blackburn, E Whooley, MA AF Hoen, Petra W. de Jonge, Peter Na, Bee Ya Farzaneh-Far, Ramin Epel, Elissa Lin, Jue Blackburn, Elizabeth Whooley, Mary A. TI Depression and Leukocyte Telomere Length in Patients With Coronary Heart Disease: Data From The Heart and Soul Study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE depression; telomere length; stable CHD ID CARDIOVASCULAR EVENTS; LONGITUDINAL FINDINGS; PHYSICAL-ACTIVITY; ARTERY-DISEASE; STRESS; VALIDITY; HEALTH; METAANALYSIS; ACTIVATION; MORTALITY AB Objective: Shortened telomere length has been associated with mortality in patients with coronary heart disease (CHD) and is considered as an emerging marker of biologic age. Whether depression is associated with telomere length or trajectory has not been evaluated in patients with CHD. Methods: In a prospective cohort study, we measured leukocyte telomere length in 952 participants with stable CHD at baseline and in 608 of these participants after 5 years of follow-up. The presence of major depressive disorder in the past month was assessed using the computerized diagnostic interview schedule at baseline. We used linear and logistic regression models to evaluate the association of depression with baseline and 5-year change in leukocyte telomere length. Results: Of the 952 participants, 206 (22%) had major depression at baseline. After the adjustment for age and sex, the patients with current major depressive disorder had shorter baseline telomere length than those without depression (mean [standard error] = 0.86 [0.02] versus 0.90 [0.01]; p = .02). This association was similar (but no longer statistically significant) after adjustment for body mass index, smoking, diabetes, left ventricular ejection fraction, statin use, antidepressant use, physical inactivity, and anxiety (0.85 [0.02] versus 0.89 [0.01], p = .06). Depression was not predictive of 5-year change in telomere length after adjustment for the mentioned covariates and baseline telomere length. Conclusions: Depression is associated with reduced leukocyte telomere length in patients with CHD but does not predict 5-year change in telomere length. Future research is necessary to elucidate the potential mechanisms underlying the association between depression and telomere length. C1 [Hoen, Petra W.; de Jonge, Peter] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 GZ Groningen, Netherlands. [de Jonge, Peter] Tilburg Univ, Dept Med Psychol, NL-5000 LE Tilburg, Netherlands. [Na, Bee Ya; Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Farzaneh-Far, Ramin; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Farzaneh-Far, Ramin] San Francisco Gen Hosp, Div Cardiol, San Francisco, CA 94110 USA. [Epel, Elissa] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Lin, Jue; Blackburn, Elizabeth] Univ San Francisco, Dept Biochem & Biophys, San Francisco, CA 94117 USA. RP Hoen, PW (reprint author), Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychiat Epidemiol, CC72,Hanzepl 1, NL-9713 GZ Groningen, Netherlands. EM p.w.hoen@med.umcg.nl RI de Jonge, peter/L-6395-2013 OI de Jonge, peter/0000-0002-0866-6929 FU Dutch Medical Research Council [016.086.397]; Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development service; National Heart Lung and Blood Institute [R01 HL079235]; American Federation for Aging Research; Robert Wood Johnson Foundation; Ischemia Research and Education Foundation; Nancy Kirwan Heart Research Fund; American Heart Association [0875014N] FX P.d.J. was supported by a VIDI Grant from the Dutch Medical Research Council (Grant 016.086.397). The Heart and Soul Study was supported by the Department of Veterans Affairs Epidemiology Merit Review Program, the Department of Veterans Affairs Health Services Research and Development service, the National Heart Lung and Blood Institute (R01 HL079235), the American Federation for Aging Research (Paul Beeson Scholars Program), the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), the Ischemia Research and Education Foundation, and the Nancy Kirwan Heart Research Fund. R.F.-F. is supported by the American Heart Association Fellow-to-Faculty Transition Award #0875014N. The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 38 TC 52 Z9 54 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP PY 2011 VL 73 IS 7 BP 541 EP 547 DI 10.1097/PSY.0b013e31821b1f6e PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 823KX UT WOS:000295122300004 PM 21597035 ER PT J AU Puterman, E O'Donovan, A Adler, NE Tomiyama, AJ Kemeny, M Wolkowitz, OM Epel, E AF Puterman, Eli O'Donovan, Aoife Adler, Nancy E. Tomiyama, A. Janet Kemeny, Margaret Wolkowitz, Owen M. Epel, Elissa TI Physical Activity Moderates Effects of Stressor-Induced Rumination on Cortisol Reactivity SO PSYCHOSOMATIC MEDICINE LA English DT Article DE acute stress; rumination; physical activity; mixed modeling; cortisol reactivity ID ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE; ALZHEIMERS-DISEASE; CARDIORESPIRATORY FITNESS; PERSEVERATIVE COGNITION; SYNAPTIC-PLASTICITY; PSYCHOSOCIAL STRESS; EXERCISE TREATMENT; MAJOR DEPRESSION; CONTROLLED-TRIAL AB Objective: Physically active individuals have lower rates of morbidity and mortality, and recent evidence indicates that physical activity may be particularly beneficial to those experiencing chronic stress. The tendency to ruminate increases and prolongs physiological stress responses, including hypothalamic-pituitary-adrenal (HPA) axis responses as indexed by cortisol reactivity to stressful experiences. We examined the association between ruminating in response to a laboratory stressor task and HPA axis reactivity and recovery and examined whether a physically active life-style moderates the associations between rumination and cortisol output trajectories. Methods: Forty-six postmenopausal women underwent the Trier Social Stress Test, whereas salivary cortisol was repeatedly measured. Twenty-five minutes after the end of the stressor, participants reported level of rumination in response to the stress. Results: Findings indicate that physical activity moderated the initial rate (B = -0.10, standard error = 0.04, p < .05) and curvature (B = -0.03, standard error = 0.01, p = .06) of the relationship between rumination and log-transformed cortisol trajectory. Among sedentary participants, those who responded to the stressor with higher levels of rumination had a more rapid initial increase in cortisol level (0.26 versus 0.21, p < .001), a later peak in cortisol reactivity (56 versus 39 minutes), and a delayed recovery from stress (curvature: -0.07 versus -0.08, p < .001) compared with those with lower levels of rumination. In active participants, cortisol trajectories were equivalent, regardless of the level of rumination. Conclusions: In sum, individuals who maintain a physically active life-style may be protected against the effects of rumination on HPA axis reactivity to and recovery from acute stress. C1 [Puterman, Eli; O'Donovan, Aoife; Adler, Nancy E.; Kemeny, Margaret; Wolkowitz, Owen M.; Epel, Elissa] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94118 USA. [O'Donovan, Aoife] San Francisco VA Med Ctr, San Francisco, CA USA. [Tomiyama, A. Janet] Rutgers State Univ, Dept Psychol, New Brunswick, NJ 08903 USA. [Tomiyama, A. Janet] Rutgers State Univ, Dept Nutr, New Brunswick, NJ 08903 USA. RP Puterman, E (reprint author), Univ Calif San Francisco, Dept Psychiat, 3333 Calif St,Suite 465, San Francisco, CA 94118 USA. EM eli.puterman@ucsf.edu OI Puterman, Eli/0000-0002-5898-2348 FU Division of Behavioral and Social Research at the National Institute on Aging/National Institutes of Health FX The research study was supported by the Division of Behavioral and Social Research at the National Institute on Aging/National Institutes of Health R56 Grant (E.E.). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 84 TC 19 Z9 19 U1 0 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP PY 2011 VL 73 IS 7 BP 604 EP 611 DI 10.1097/PSY.0b013e318229e1e0 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 823KX UT WOS:000295122300012 PM 21873586 ER PT J AU Gottlieb, JD Cather, C Shanahan, M Creedon, T Macklin, EA Goff, DC AF Gottlieb, Jennifer D. Cather, Corinne Shanahan, Meghan Creedon, Timothy Macklin, Eric A. Goff, Donald C. TI D-cycloserine facilitation of cognitive behavioral therapy for delusions in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE NMDA receptor hypofunction; D-cycloserine; Cognitive-behavioral therapy; Psychosis; Delusions; Schizophrenia ID NMDA; EXTINCTION; RECEPTOR; MEMORY; FEAR; RETENTION; FRAMEWORK; BIOLOGY; TASK AB Glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction has been proposed as a mechanism underlying psychosis. D-cycloserine, a partial agonist at the glycine site of the NMDA receptor, enhances learning in animal models, although tachyphylaxis develops with repeated dosing. Once-weekly dosing of D-cycloserine produces persistent improvement when combined with cognitive behavioral therapy (CBT) in anxiety disorders. Delusional beliefs can be conceptualized as a learning deficit, characterized by the failure to use contradictory evidence to modify the belief. CBT techniques have been developed with modest success to facilitate such reality-testing (or new learning) in delusional beliefs. The current study evaluated whether D-cycloserine could potentiate beneficial effects of CBT on delusional severity. Twenty-one outpatients with schizophrenia or schizoaffective disorder and moderately severe delusions were randomized in a double-blind cross-over design to receive a single-dose of either D-cycloserine 50 mg or placebo in a counterbalanced order on two consecutive weeks 1 h prior to a CBT intervention involving training in the generation of alternative beliefs. Assessments were completed at baseline, 7 days following the first study drug administration and 7 days following the second study drug administration. Contrary to prediction, there was no significant D-cycloserine treatment effect on delusional distress or severity as measured by the SAPS or PSYRATS. An unexpected finding was an order effect, whereby subjects who received D-cycloserine first had significantly reduced delusional severity, distress, and belief conviction on PSYRATS compared to subjects who received placebo first. However, this finding is consistent with animal models in which D-cycloserine enhances learning only when accompanying the first exposure to training. (C) 2011 Elsevier B.V. All rights reserved. C1 [Gottlieb, Jennifer D.] Dartmouth Psychiat Res Ctr, Dept Psychiat, Dartmouth Med Sch, Concord, NH 03301 USA. [Gottlieb, Jennifer D.; Cather, Corinne; Shanahan, Meghan; Creedon, Timothy; Goff, Donald C.] Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, Boston, MA 02114 USA. [Cather, Corinne; Macklin, Eric A.; Goff, Donald C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Gottlieb, JD (reprint author), Dartmouth Psychiat Res Ctr, Dept Psychiat, Dartmouth Med Sch, 105 Pleasant St, Concord, NH 03301 USA. EM Jennifer.D.Gottlieb@dartmouth.edu RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 FU Harvard Medical School [K24 MH002025, P50 MH60450]; NIMH [5K24 MH002025-10]; NIMH Neuroscience Center [5 P50 MH60450-11] FX Funding for this study was provided by a departmental grant from Harvard Medical School (JDG), K24 MH002025 (DCG) and P50 MH60450 (Joseph Coyle, PI).; Funding for this study was provided in part by a departmental grant from Harvard Medical School, awarded to the first author (PI: J.D. Gottlieb). Additional grant funding was provided by an NIMH K-Award of D. Gaffs (5K24 MH002025-10; "New Treatment Approaches in Schizophrenia:" PI: D. Goff) and via an NIMH Neuroscience Center grant (Neuroscience Center #5 P50 MH60450-11; "Glutamate Dysregulation in Schizophrenia", Silvio Conte Neuroscience Center; PI: J. Coyle: Co-Investigator: D. Goff). The funding sources had no involvement in the decision to write the paper or in the decision to submit the paper for publication. NR 26 TC 32 Z9 32 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2011 VL 131 IS 1-3 BP 69 EP 74 DI 10.1016/j.schres.2011.05.029 PG 6 WC Psychiatry SC Psychiatry GA 823GV UT WOS:000295111400012 PM 21723096 ER PT J AU Dickey, CC Panych, LP Voglmaier, MM Niznikiewicz, MA Terry, DP Murphy, C Zacks, R Shenton, ME McCarley, RW AF Dickey, Chandlee C. Panych, Lawrence P. Voglmaier, Martina M. Niznikiewicz, Margaret A. Terry, Douglas P. Murphy, Cara Zacks, Rayna Shenton, Martha E. McCarley, Robert W. TI Facial emotion recognition and facial affect display in schizotypal personality disorder SO SCHIZOPHRENIA RESEARCH LA English DT Article ID GENERALIZED POOR PERFORMANCE; SCHIZOPHRENIA-PATIENTS; FACE PERCEPTION; SOCIAL BRAIN; DEFICITS; EXPRESSIONS; IMPAIRMENT; COGNITION; FAMILY; DISCRIMINATION AB Background: Patients with schizophrenia have deficits in facial affect expression and detection that hinder social interactions. The goal of this study was to examine whether or not epidemiologically-related antipsychotic-naive schizotypal personality disorder (SPD) subjects would have similar deficits as patients with schizophrenia. Methods: Matched SPD and healthy comparison (HC) subjects were asked to identify the eight classic emotions (SPD N = 55, HC N = 67) and to discriminate gender. Subjects (SPD N = 22, HC N = 17) were also photographed while displaying the same emotional expressions. Raters scored the subjects' facial expressions along several dimensions. Results: SPD subjects compared with HC were slower and less accurate in identifying facial expressions. This may have been driven by deficits in identifying gender. Although raters were able to identify correctly SPD and HC subjects' expressions equally well, raters found SPD subjects' facial expressions to be more odd, more ambiguous, and the subjects less attractive in general compared with HC subjects. Raters were less confident in their ability to correctly interpret SPD subjects' facial expressions and raters were less comfortable with the idea of spending time with the SPD subjects compared with HC subjects. Conclusions: SPD subjects face two hurdles in terms of daily social interactions. They have problems both in correctly interpreting others' facial expressions and in generating socially attractive and unambiguous facial expressions. Published by Elsevier B.V. C1 [Dickey, Chandlee C.; Niznikiewicz, Margaret A.; Shenton, Martha E.; McCarley, Robert W.] VA Boston Healthcare Syst, Dept Psychiat, Psychiat 116A7, Brockton, MA 02301 USA. [Dickey, Chandlee C.; Voglmaier, Martina M.; Niznikiewicz, Margaret A.; Murphy, Cara; Zacks, Rayna; Shenton, Martha E.; McCarley, Robert W.] VA Boston Healthcare Syst, Neurosci Lab, Brockton, MA 02301 USA. [Dickey, Chandlee C.; Niznikiewicz, Margaret A.; Terry, Douglas P.; Shenton, Martha E.] Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Boston, MA 02215 USA. [Panych, Lawrence P.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02216 USA. RP Dickey, CC (reprint author), VA Boston Healthcare Syst, Dept Psychiat, Psychiat 116A7, 940 Belmont St, Brockton, MA 02301 USA. EM chandlee_dickey@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU Department of Veterans Affairs; National Institute of Mental Health (NIMH) [R21MH077979, RO1 MH52807]; VA Boston Healthcare System FX The project described was supported by the Department of Veterans Affairs and by NIMH Award Numbers R21MH077979 (CCD) and RO1 MH52807 (RWM) from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, or the Department of Veterans Affairs.; The authors would like to thank Jorge Alvarado, Laurel Bobrow, Diandra Lucia, Andrew Rausch, Tali Swisher, and Rebecca D. King for their ratings of facial expressions, and Lori Benjamin for her administrative support The project described was supported by the VA Boston Healthcare System and Award Number R21 MH077979 from the National Institute of Mental Health. NR 70 TC 14 Z9 14 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2011 VL 131 IS 1-3 BP 242 EP 249 DI 10.1016/j.schres.2011.04.020 PG 8 WC Psychiatry SC Psychiatry GA 823GV UT WOS:000295111400038 PM 21640557 ER PT J AU D'Addio, F Ueno, T Clarkson, M Zhu, BG Freeman, GJ Sayegh, MH Ansari, JI Habicht, A AF D'Addio, Francesca Ueno, Takuya Clarkson, Michael Zhu, Baogong Freeman, Gordon J. Sayegh, Mohamed H. Ansari, Javeed I. Habicht, Antje TI CD160Ig FUSION PROTEIN TARGETS A NOVEL COSTIMULATORY PATHWAY AND PROLONGS ALLOGRAFT SURVIVAL SO TRANSPLANT INTERNATIONAL LA English DT Meeting Abstract C1 [D'Addio, Francesca; Ueno, Takuya; Clarkson, Michael; Sayegh, Mohamed H.; Ansari, Javeed I.; Habicht, Antje] Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. [D'Addio, Francesca; Ueno, Takuya; Clarkson, Michael; Sayegh, Mohamed H.; Ansari, Javeed I.; Habicht, Antje] Childrens Hosp, Boston, MA 02115 USA. [Zhu, Baogong; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Clarkson, Michael] Cork Univ Hosp, Dept Renal Med, Cork, Ireland. [Habicht, Antje] Univ Hosp Munich Grosshadern, Transplant Ctr Munich, Munich, Germany. RI D'Addio, Francesca/F-3417-2017 OI D'Addio, Francesca/0000-0002-0345-0694 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD SEP PY 2011 VL 24 SU 2 SI SI BP 97 EP 98 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 819YA UT WOS:000294869600334 ER PT J AU Tena, A Turcotte, N Barone, AAL Arn, S Terlouw, SL Dobrinsky, JR Sachs, DH Hawley, RJ AF Tena, Aseda Turcotte, Nicole Barone, Angelo A. Leto Arn, Scott Terlouw, Steven L. Dobrinsky, John R. Sachs, David H. Hawley, Robert J. TI Miniature swine expressing human CD47 to enhance bone marrow engraftment in non-human primates SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the Cell-Transplant-Society(CTS)/International-Xenotransplantation-Associati on (IXA) CY OCT 23-26, 2011 CL Miami, FL SP Cell Transplant Soc, Int Xenotransplantat Assoc C1 [Tena, Aseda; Turcotte, Nicole; Barone, Angelo A. Leto; Arn, Scott; Sachs, David H.; Hawley, Robert J.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Terlouw, Steven L.; Dobrinsky, John R.] Minitube Amer, Genet, Verona, WI USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2011 VL 18 IS 5 SI SI BP 271 EP 271 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 823AJ UT WOS:000295092900011 ER PT J AU Zhao, GP Kim, J Lee, KM O'Connor, M Yang, MZ Lei, J Schuetz, C Markmann, J Deng, SP AF Zhao, Gaoping Kim, James Lee, Kang Mi O'Connor, Matthew Yang, Maozhu Lei, Ji Schuetz, Christian Markmann, James Deng, Shaoping TI Roles of B cells and Tregs in anti-CD45RB induced transplant tolerance to islet xenografts SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the Cell-Transplant-Society(CTS)/International-Xenotransplantation-Associati on (IXA) CY OCT 23-26, 2011 CL Miami, FL SP Cell Transplant Soc, Int Xenotransplantat Assoc C1 [Zhao, Gaoping; Kim, James; Lee, Kang Mi; O'Connor, Matthew; Yang, Maozhu; Lei, Ji; Schuetz, Christian; Markmann, James; Deng, Shaoping] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhao, Gaoping; Yang, Maozhu; Deng, Shaoping] Sichuan Prov Peoples Hosp, Chengdu, Sichuan, Peoples R China. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2011 VL 18 IS 5 SI SI BP 274 EP 274 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 823AJ UT WOS:000295092900021 ER PT J AU Machaidze, Z Wei, LL Yeh, H Schuetz, C Carvello, M Peng, Q Lei, J Deng, SP Smith, R Sachs, DH Markmann, J Buhler, L AF Machaidze, Zurab Wei, Lingling Yeh, Heidi Schuetz, Christian Carvello, Michele Peng, Qiang Lei, Ji Deng, Shaoping Smith, Rex Sachs, David H. Markmann, James Buhler, Leo TI Transplantation of encapsulated porcine hepatocytes improves metabolic function and survival in baboons with acute liver failure SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the Cell-Transplant-Society(CTS)/International-Xenotransplantation-Associati on (IXA) CY OCT 23-26, 2011 CL Miami, FL SP Cell Transplant Soc, Int Xenotransplantat Assoc C1 [Machaidze, Zurab; Wei, Lingling; Yeh, Heidi; Schuetz, Christian; Carvello, Michele; Peng, Qiang; Lei, Ji; Deng, Shaoping; Markmann, James; Buhler, Leo] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. [Smith, Rex] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sachs, David H.] Massachusetts Gen Hosp, Transplant Biol Res Ctr, Boston, MA 02114 USA. [Buhler, Leo] Univ Hosp Geneva, Dept Surg, Geneva, Switzerland. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2011 VL 18 IS 5 SI SI BP 284 EP 284 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 823AJ UT WOS:000295092900054 ER PT J AU Peng, Q Yeh, H Enjoji, K Machaidze, Z Wei, LL Csizmad, E Schuetz, C Deng, SP Markmann, J Robson, S Buhler, L AF Peng, Qiang Yeh, Heidi Enjoji, Keiichi Machaidze, Zurab Wei, Lingling Csizmad, Eva Schuetz, Christian Deng, Shaoping Markmann, James Robson, Simon Buhler, Leo TI Integrin dependent baboon platelet activation and phagocytosis by porcine hepatocytes and endothelial cells SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the Cell-Transplant-Society(CTS)/International-Xenotransplantation-Associati on (IXA) CY OCT 23-26, 2011 CL Miami, FL SP Cell Transplant Soc, Int Xenotransplantat Assoc C1 [Peng, Qiang; Yeh, Heidi; Machaidze, Zurab; Wei, Lingling; Schuetz, Christian; Deng, Shaoping; Markmann, James; Buhler, Leo] Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA 02114 USA. [Enjoji, Keiichi; Csizmad, Eva; Robson, Simon] Beth Israel Deaconess Med Ctr, Dept Gastroenterol, Boston, MA 02215 USA. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2011 VL 18 IS 5 SI SI BP 287 EP 288 PG 3 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 823AJ UT WOS:000295092900066 ER PT J AU Wang, YT Wang, H Fu, YW Yang, YG AF Wang, Yuantao Wang, Hui Fu, Yaowen Yang, Yongguang TI Rapid DC activation and diminished tolerance induction in mice treated with CD47-deficient DST and CD40/CD154 costimulatory blockade SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the Cell-Transplant-Society(CTS)/International-Xenotransplantation-Associati on (IXA) CY OCT 23-26, 2011 CL Miami, FL SP Cell Transplant Soc, Int Xenotransplantat Assoc C1 [Wang, Yuantao; Fu, Yaowen] Jilin Univ, Bethune Hosp 1, Urinary Dis Diag & Treatment Ctr, Changchun 130023, Jilin, Peoples R China. [Wang, Yuantao; Wang, Hui; Yang, Yongguang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Wang, Hui; Yang, Yongguang] Columbia Univ, Coll Phys & Surg, Columbia Ctr Translat Immunol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2011 VL 18 IS 5 SI SI BP 310 EP 310 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 823AJ UT WOS:000295092900140 ER PT J AU Schuetz, C Kim, K Elias, N Veillette, G Wamala, I Smith, R Robson, S Cosimi, B Sachs, D Hertl, M AF Schuetz, Christian Kim, Karen Elias, Nahel Veillette, Gregory Wamala, Isaac Smith, Rex Robson, Simon Cosimi, Benedict Sachs, David Hertl, Martin TI 9-day survival and control of thrombocytopenia following liver xenotransplantation in baboons using GalT-KO swine grafts SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint International Congress of the Cell-Transplant-Society(CTS)/International-Xenotransplantation-Associati on (IXA) CY OCT 23-26, 2011 CL Miami, FL SP Cell Transplant Soc, Int Xenotransplantat Assoc C1 [Schuetz, Christian; Kim, Karen; Elias, Nahel; Veillette, Gregory; Wamala, Isaac; Cosimi, Benedict; Sachs, David; Hertl, Martin] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Smith, Rex] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Robson, Simon] Beth Israel Deaconess Med Ctr, Dept Gastroenterol, Boston, MA USA. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2011 VL 18 IS 5 SI SI BP 314 EP 314 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 823AJ UT WOS:000295092900154 ER PT J AU Castranova, D Lawton, A Lawrence, C Baumann, DP Best, J Coscolla, J Doherty, A Ramos, J Hakkesteeg, J Wang, CM Wilson, C Malley, J Weinstein, BM AF Castranova, Daniel Lawton, Angela Lawrence, Christian Baumann, Diana P. Best, Jason Coscolla, Jordi Doherty, Amy Ramos, Juan Hakkesteeg, Jenna Wang, Chongmin Wilson, Carole Malley, James Weinstein, Brant M. TI The Effect of Stocking Densities on Reproductive Performance in Laboratory Zebrafish (Danio rerio) SO ZEBRAFISH LA English DT Article ID SALVELINUS-ALPINUS; CROWDING STRESS; ARCTIC CHARR; GROWTH; JUVENILES AB Despite the growing popularity of the zebrafish model system, the optimal husbandry conditions for this animal are not well defined. The aim of this study was to examine the effect of stocking density on reproductive performance in zebrafish. In this study, undertaken by eight different zebrafish facilities, clutches of at least 200 wild-type zebrafish embryos from a single pairwise mating were produced at each participating institution and subsequently reared according to "in-house protocols'' until they were 14 weeks old. Fish were then randomly assigned into treatment groups with balanced sex ratios and densities of 3, 6, or 12 fish/L. After a 1-month acclimation period, fish were spawned in pair crosses every 2 weeks for 3 months, for a total of six spawning dates. The number of viable and nonviable embryos produced in each clutch were counted at 1 day post-fertilization. Although there was a great deal of variability in clutch size and percent spawning success among laboratories, there were no significant differences in average clutch size, spawning success, or percent viable among the treatment densities. These data suggest that using stocking densities as high as 12 fish/L does not have a negative impact on performance, when measured by reproductive performance. C1 [Castranova, Daniel; Wang, Chongmin; Weinstein, Brant M.] NICHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. [Lawton, Angela] Univ Queensland, Brisbane, Qld 4072, Australia. [Lawrence, Christian; Best, Jason] Childrens Hosp Boston, Boston, MA USA. [Baumann, Diana P.] Stowers Inst Med Res, Kansas City, MO USA. [Coscolla, Jordi; Ramos, Juan] Barcelona Biomed Res Pk, Barcelona, Spain. [Doherty, Amy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hakkesteeg, Jenna; Wilson, Carole] UCL, London, England. [Malley, James] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Weinstein, BM (reprint author), NICHD, Program Genom Differentiat, NIH, Bldg 6B,Room 413,6 Ctr Dr, Bethesda, MD 20892 USA. EM castrand@mail.nih.gov; flyingfish2@nih.gov RI Zebrafish, UCL/A-3125-2009 NR 16 TC 11 Z9 11 U1 1 U2 17 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-8547 J9 ZEBRAFISH JI Zebrafish PD SEP PY 2011 VL 8 IS 3 BP 141 EP 146 DI 10.1089/zeb.2011.0688 PG 6 WC Developmental Biology; Zoology SC Developmental Biology; Zoology GA 822GL UT WOS:000295031900006 PM 21854208 ER PT J AU Wagner, BK Gilbert, TJ Hanai, J Imamura, S Bodycombe, NE Bon, RS Waldmann, H Clemons, PA Sukhatme, VP Mootha, VK AF Wagner, Bridget K. Gilbert, Tamara J. Hanai, Jun-ichi Imamura, Shintaro Bodycombe, Nicole E. Bon, Robin S. Waldmann, Herbert Clemons, Paul A. Sukhatme, Vikas P. Mootha, Vamsi K. TI A Small-Molecule Screening Strategy To Identify Suppressors of Statin Myopathy SO ACS CHEMICAL BIOLOGY LA English DT Article ID GERANYLGERANYLATION; INHIBITORS; RAT; FARNESYLTRANSFERASE; CHOLESTEROL; PRAVASTATIN; METABOLISM AB The reduction of plasma low-density lipoprotein levels by HMG-CoA reductase inhibitors, or statins, has had a revolutionary impact in medicine, but muscle-related side effects remain a dose-limiting toxicity in many patients. We describe a chemical epistasis approach that can be useful in refining the mechanism of statin muscle toxicity, as well as in screening for agents that suppress muscle toxicity while preserving the ability of statins to increase the expression of the low-density lipoprotein receptor. Using this approach, we identified one compound that attenuates the muscle side effects in both cellular and animal models of statin toxicity, likely by influencing Rab prenylation. Our proof-of-concept screen lays the foundation for truly high-throughput screens that could help lead to the development of clinically useful adjuvants that can one day be co-administered with statins. C1 [Wagner, Bridget K.; Gilbert, Tamara J.; Bodycombe, Nicole E.; Clemons, Paul A.; Mootha, Vamsi K.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. [Hanai, Jun-ichi; Sukhatme, Vikas P.] Beth Israel Deaconess Med Ctr, Dept Med, Div Renal, Boston, MA 02215 USA. [Hanai, Jun-ichi; Sukhatme, Vikas P.] Beth Israel Deaconess Med Ctr, Dept Med, Div Interdisciplinary Med & Biotechnol, Boston, MA 02215 USA. [Imamura, Shintaro] Natl Res Inst Fisheries Sci, Food Technol & Biochem Div, Yokohama, Kanagawa, Japan. [Bon, Robin S.; Waldmann, Herbert] Max Planck Inst Mol Physiol, Dept Chem Biol, D-44139 Dortmund, Germany. [Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Wagner, BK (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA. EM bwagner@broadinstitute.org; vamsi@hms.harvard.edu OI Bon, Robin/0000-0003-1733-3680; Waldmann, Herbert/0000-0002-9606-7247 FU Howard Hughes Medical Institute; Alexander von Humboldt Stiftung; National Institutes of Health [R24 DK-080261, DP2 DK-083048] FX We thank N. Doro, Z. Gauhar, and K. Hartland for technical assistance; M. Freeman, R. Gould, T. Kitami, and S. Shaw for helpful comments; and the Broad Chemical Biology Platform for compound arraying. This work was supported by fellowships or grants from the Howard Hughes Medical Institute (V.K.M.), the Alexander von Humboldt Stiftung (to R.S.B.), and the National Institutes of Health (R24 DK-080261 to V.K.M. and DP2 DK-083048 to B.K.W.). NR 24 TC 8 Z9 8 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD SEP PY 2011 VL 6 IS 9 BP 900 EP 904 DI 10.1021/cb200206w PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 819ZI UT WOS:000294874600005 PM 21732624 ER PT J AU Lane, AM Kim, IK Gragoudas, ES AF Lane, Anne Marie Kim, Ivana K. Gragoudas, Evangelos S. TI Proton Irradiation for Peripapillary and Parapapillary Melanomas SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID JUXTAPAPILLARY CHOROIDAL MELANOMA; STEREOTACTIC RADIOTHERAPY; PLAQUE RADIOTHERAPY; OPTIC DISC AB Objective: To examine ocular outcomes and survival after proton irradiation in patients with peripapillary and parapapillary melanomas ineligible for the Collaborative Ocular Melanoma Study. Methods: A total of 573 patients who received proton irradiation from January 4, 1985, through December 24, 1997, for tumors located within 1 disc diameter of the optic nerve, and therefore ineligible for the Collaborative Ocular Melanoma Study, were evaluated. Cumulative rates of vision loss in the treated eye, eye loss, melanoma-related mortality, and tumor recurrence were estimated using the Kaplan-Meier method. Results: Most (53.4%) tumors abutted the optic disc; median distance from the tumor to the macula was 0.5 disc diameters. By 5 years after proton therapy, radiation papillopathy had developed in 56.8% and maculopathy in 60.4% of patients. Of 450 patients with a base-line visual acuity of 20/200 or better in the treated eye, vision was retained in 54.9% at 2 years after irradiation. This decreased to 20.3% by 5 years after treatment, although 56.2% had visual acuity of counting fingers or better. Five- and 10-year rates of local recurrence were 3.3% and 6.0%, respectively. Enucleation rates were 13.3% at 5 years and 17.1% at 10 years after treatment. Melanoma-related mortality rates were similar to those in our larger cohort of patients (24.0% at 15 years). Conclusions: Proton irradiation should be considered for treating patients with tumors contiguous to the optic disc. Although visual acuity is compromised, some preservation is possible (counting fingers or better in many patients). Eye conservation is likely, with low rates of tumor recurrence and no increased risk of metastasis. C1 [Lane, Anne Marie; Kim, Ivana K.; Gragoudas, Evangelos S.] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RP Lane, AM (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM alane@meei.harvard.edu FU MEEI; Grimshaw-Gudewicz Charitable Foundation; Research to Prevent Blindness FX This research was funded in part by the MEEI Melanoma Research Fund, the Grimshaw-Gudewicz Charitable Foundation, and Research to Prevent Blindness (Dr Kim). NR 10 TC 10 Z9 10 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 2011 VL 129 IS 9 BP 1127 EP 1130 PG 4 WC Ophthalmology SC Ophthalmology GA 819YQ UT WOS:000294872000001 PM 21911661 ER PT J AU Liu, DP Zhou, XH AF Liu, Danping Zhou, Xiao-Hua TI Semiparametric Estimation of the Covariate-Specific ROC Curve in Presence of Ignorable Verification Bias SO BIOMETRICS LA English DT Article DE Alzheimer's disease; Covariate-specific ROC curve; Ignorable missingness; Verification bias; Weighted estimating equations ID ASSESSING ACCURACY; DIAGNOSTIC-TESTS; DISEASE; LIKELIHOOD; DEMENTIA; AREA AB Covariate-specific receiver operating characteristic (ROC) curves are often used to evaluate the classification accuracy of a medical diagnostic test or a biomarker, when the accuracy of the test is associated with certain covariates. In many large-scale screening tests, the gold standard is subject to missingness due to high cost or harmfulness to the patient. In this article, we propose a semiparametric estimation of the covariate-specific ROC curves with a partial missing gold standard. A location-scale model is constructed for the test result to model the covariates' effect, but the residual distributions are left unspecified. Thus the baseline and link functions of the ROC curve both have flexible shapes. With the gold standard missing at random (MAR) assumption, we consider weighted estimating equations for the location-scale parameters, and weighted kernel estimating equations for the residual distributions. Three ROC curve estimators are proposed and compared, namely, imputation-based, inverse probability weighted, and doubly robust estimators. We derive the asymptotic normality of the estimated ROC curve, as well as the analytical form of the standard error estimator. The proposed method is motivated and applied to the data in an Alzheimer's disease research. C1 [Liu, Danping; Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence, Seattle, WA 98108 USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM dpliu@u.washington.edu; azhou@u.washington.edu RI Liu, Danping/D-2544-2013 FU NIH/NIA [U01AG016976, NSFC30728019] FX The work was supported in part by NIH/NIA grant U01AG016976 and NSFC30728019. This article does not necessarily represent the findings and conclusions of VA HSR&D. Dr X-HZ is presently a Core Investigator and Biostatistics Unit Director at HSR&D Center of Excellence, Department of Veterans Affairs Puget Sound Health Care System, Seattle, Washington. NR 21 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2011 VL 67 IS 3 BP 906 EP 916 DI 10.1111/j.1541-0420.2011.01562.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 819XE UT WOS:000294866800024 PM 21361890 ER PT J AU Bellon, JR Harris, EER Arthur, DW Bailey, L Carey, L Goyal, S Halyard, MY Horst, KC Moran, MS MacDonald, SM Haffty, BG AF Bellon, Jennifer R. Harris, Eleanor E. R. Arthur, Douglas W. Bailey, Lisa Carey, Lisa Goyal, Sharad Halyard, Michele Y. Horst, Kathleen C. Moran, Meena S. MacDonald, Shannon M. Haffty, Bruce G. TI ACR Appropriateness Criteria (R) Conservative surgery and Radiation - Stage I and II Breast Carcinoma SO BREAST JOURNAL LA English DT Article DE appropriateness criteria; breast conservation; radiation therapy ID 20-YEAR FOLLOW-UP; RANDOMIZED-TRIAL; CONSERVING SURGERY; ADJUVANT CHEMOTHERAPY; CONTRALATERAL BREAST; RADIOTHERAPY HYPOFRACTIONATION; UK STANDARDIZATION; LOCAL RECURRENCE; TUMOR RECURRENCE; TOTAL MASTECTOMY AB Breast conservation is a safe and effective alternative to mastectomy for the majority of women with early-stage breast cancer. Adjuvant radiation therapy lowers the risk of recurrence within the breast and also confers a survival benefit. Although acute side effects of radiation therapy are generally well tolerated; efforts are ongoing to minimize the long-term side effects of radiation, most prominently atherosclerotic heart disease. Efforts to minimize radiation therapy are also underway. They include omitting treatment altogether in the elderly and using accelerated, hypofractionated whole-breast irradiation, and accelerated partial-breast irradiation. Several randomized studies are ongoing to determine the efficacy, safety, and appropriate patients for these shorter treatments. C1 [Bellon, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bellon, Jennifer R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Harris, Eleanor E. R.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Arthur, Douglas W.] Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. [Bailey, Lisa] Amer Coll Surg, Alta Bates Summit Med Ctr, Oakland, CA USA. [Carey, Lisa] Univ N Carolina Hlth Care Syst, Amer Soc Clin Oncol, Chapel Hill, NC USA. [Goyal, Sharad; Haffty, Bruce G.] UMDNJ Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Halyard, Michele Y.] Mayo Clin, Scottsdale, AZ USA. [Horst, Kathleen C.] Stanford Canc Ctr, Palo Alto, CA USA. [Moran, Meena S.] Yale Univ, Sch Med, New Haven, CT USA. [MacDonald, Shannon M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bellon, JR (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jbellon@lroc.harvard.edu NR 51 TC 13 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1075-122X EI 1524-4741 J9 BREAST J JI Breast J. PD SEP-OCT PY 2011 VL 17 IS 5 BP 448 EP 455 DI 10.1111/j.1524-4741.2011.01132.x PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 821MN UT WOS:000294979200002 PM 21790842 ER PT J AU Cotter, SE Chen, MH Moul, JW Lee, WR Koontz, BF Anscher, MS Robertson, CN Walther, PJ Polascik, TJ D'Amico, AV AF Cotter, Shane E. Chen, Ming Hui Moul, Judd W. Lee, W. Robert Koontz, Bridget F. Anscher, Mitchell S. Robertson, Cary N. Walther, Philip J. Polascik, Thomas J. D'Amico, Anthony V. TI Salvage Radiation in Men After Prostate-Specific Antigen Failure and the Risk of Death SO CANCER LA English DT Article DE prostate cancer; radiation therapy; salvage; radical prostatectomy ID CANCER-SPECIFIC MORTALITY; RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; DOUBLING TIME; RADIOTHERAPY; COMORBIDITY; PROGRESSION AB BACKGROUND: A survival benefit has been observed with salvage radiation therapy (RT) for prostate-specific antigen (PSA) failure after radical prostatectomy (RP) in men with rapid rises in PSA doubling time (DT, < 6 months). Whether such a benefit exits in men with a protracted PSA rise in DT (>= 6 months) is unclear and was examined in the current study. METHODS: Of 4036 men who underwent RP at Duke University between 1988 and 2008, 519 experienced a PSA failure, had complete data, and were the subjects of this study. Univariate and multivariate Cox regression analyses were performed to evaluate whether salvage RT in men with either a rapid (< 6 months) or a protracted (>= 6 months) PSA DT was associated with the risk of all-cause mortality adjusting for age at the time of PSA failure, known prostate cancer prognostic factors, and cardiac comorbidity. RESULTS: After a median follow-up of 11.3 years after PSA failure, 195 men died. Salvage RT was associated with a significant reduction in all-cause mortality for men with either a PSA DT of < 6 months (adjusted hazard ratio [AHR], 0.53; P = .02) or a PSA DT of >= 6 months (AHR, 0.52; P = .003). In a subset of patients with comorbidity data at the time of PSA failure, salvage RT remained associated with a significant reduction in all-cause mortality for both men with a PSA DT of < 6 months (AHR, 0.35; P = .042) or a PSA DT of >= 6 months (AHR, 0.60; P = .04). CONCLUSIONS: Salvage RT for PSA DTs less than or in excess of 6 months is associated with a decreased risk in all-cause mortality. Cancer 2011; 117: 3925-32. (C) 2011 American Cancer Society. C1 [Cotter, Shane E.] Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Chen, Ming Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Moul, Judd W.; Robertson, Cary N.; Walther, Philip J.; Polascik, Thomas J.] Duke Univ, Div Urol Surg, Durham, NC USA. [Moul, Judd W.; Robertson, Cary N.; Walther, Philip J.; Polascik, Thomas J.] Duke Univ, Duke Prostate Ctr, Dept Surg, Durham, NC USA. [Lee, W. Robert; Koontz, Bridget F.] Duke Univ, Dept Radiat Oncol, Durham, NC USA. [Anscher, Mitchell S.] Virginia Commonwealth Univ, Dept Radiat Oncol, Richmond, VA USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Cotter, SE (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Harvard Radiat Oncol Program, 75 Francis St,ASB1 L2, Boston, MA 02115 USA. EM scotter@partners.org OI Anscher, Mitchell/0000-0003-4480-111X NR 22 TC 43 Z9 44 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2011 VL 117 IS 17 BP 3925 EP 3932 DI 10.1002/cncr.25993 PG 8 WC Oncology SC Oncology GA 820SD UT WOS:000294924800015 PM 21437885 ER PT J AU Atochin, DN Huang, PL AF Atochin, Dmitriy N. Huang, Paul L. TI Role of Endothelial Nitric Oxide in Cerebrovascular Regulation SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE Cerebrovascular regulation; endothelial nitric oxide synthase; mutant mice ID CEREBRAL-BLOOD-FLOW; AKT-DEPENDENT ACTIVATION; SYNTHASE GENE-EXPRESSION; COA REDUCTASE INHIBITOR; PROTEIN-KINASE AKT; NOS KNOCKOUT MICE; RHO-KINASE; SMOOTH-MUSCLE; MUTANT MICE; STROKE PROTECTION AB Endothelial nitric oxide (NO) plays important roles in the vascular system. Animal models that show vascular dysfunction demonstrate the protective role of endothelial NO dependent pathways. This review focuses on the role of endothelial NO in the regulation of cerebral blood flow and vascular tone. We will discuss the importance of NO in cerebrovascular function using animal models with altered endothelial NO production under normal, ischemic and reperfusion conditions, as well as in hyperoxia. Pharmacological and genetic manipulations of the endothelial NO system demonstrate the essential roles of endothelial NO synthase in maintenance of vascular tone and cerebral perfusion under normal and pathological conditions. C1 [Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02129 USA. [Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. EM phuang1@partners.org RI Atochin, Dmitriy/Q-3150-2016 FU AHA [SDG 0835344N]; NIH [R01-NS033335] FX This work was supported by the AHA (SDG 0835344N) and the NIH (R01-NS033335) grants. NR 109 TC 8 Z9 8 U1 0 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 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD SEP PY 2011 VL 12 IS 9 BP 1334 EP 1342 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 820HO UT WOS:000294896500006 PM 21235451 ER PT J AU Deng, M Kwiatkowski, TJ Fan, D Zhang, J Zhang, N Tang, L AF Deng, M. Kwiatkowski, T. J., Jr. Fan, D. Zhang, J. Zhang, N. Tang, L. TI TARDBP GENE MUTATIONS IN CHINESE PATIENTS WITH FAMILIAL AMYOTROPHIC LATERAL SCLEROSIS SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 15th Congress of the European-Federation-of-Neurological-Societies (EFNS) CY SEP 10-13, 2011 CL Budapest, HUNGARY SP European Federat Neurol Soc C1 [Deng, M.] Peking Univ, Hosp 3, Dept Neurol, Beijing 100871, Peoples R China. [Kwiatkowski, T. J., Jr.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2011 VL 18 SU 2 SI SI BP 229 EP 229 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 819DW UT WOS:000294806600421 ER PT J AU Bajor, LA Ticlea, AN Osser, DN AF Bajor, Laura A. Ticlea, Ana Nectara Osser, David N. TI The Psychopharmacology Algorithm Project at the Harvard South Shore Program: An Update on Posttraumatic Stress Disorder SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE algorithms; posttraumatic stress disorder; psychopharmacology; stress disorders ID PLACEBO-CONTROLLED-TRIAL; VENLAFAXINE EXTENDED-RELEASE; OPEN-LABEL TRIAL; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; COMBAT VETERANS; QUETIAPINE TREATMENT; SLEEP DISTURBANCES; ADJUNCTIVE THERAPY; MAJOR DEPRESSION AB Background: This project aimed to provide an organized, sequential, and evidence-supported approach to the pharmacotherapy of posttraumatic stress disorder (PTSD), following the format of previous efforts of the Psychopharmacology Algorithm Project at the Harvard South Shore Program. Method: A comprehensive literature review was conducted to determine the best pharmacological choices for PTSD patients and to update the last published version (1999) of the algorithm. We focused on optimal pharmacological interventions to address the prominent symptoms of PTSD, with additional attention to the impact that common comorbidities have on treatment choices. Results: We found that SSRIs and SNRIs are not as effective as previously thought, and that awareness of their long-term side effects has increased. New evidence suggests that addressing fragmented sleep and nightmares can improve symptoms (in addition to insomnia) that are frequently seen with PTSD (e. g., hyperarousal, reexperiencing). Prazosin and trazodone are emphasized at this initial step; if significant PTSD symptoms remain, an antidepressant may be tried. For PTSD-related psychosis, an antipsychotic may be added. In resistant cases, two or three antidepressants may be used in sequence. Following that, or with partial improvement and residual symptomatology, augmentation may be tried; the best options are antipsychotics, clonidine, topiramate, and lamotrigine. Conclusion: This heuristic may be helpful in producing faster symptom resolution, fewer side effects, and increased compliance. (HARV REV PSYCHIATRY 2011; 19: 240-258.) C1 [Osser, David N.] VA Boston Healthcare Syst, Brockton Div, Brockton, MA 02301 USA. [Bajor, Laura A.; Ticlea, Ana Nectara] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Bajor, Laura A.; Ticlea, Ana Nectara] Harvard S Shore Psychiat Residency Training Progr, Brockton, MA USA. RP Osser, DN (reprint author), VA Boston Healthcare Syst, Brockton Div, 940 Belmont St, Brockton, MA 02301 USA. EM David.Osser@va.gov NR 146 TC 26 Z9 27 U1 7 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 2011 VL 19 IS 5 BP 240 EP 258 DI 10.3109/10673229.2011.614483 PG 19 WC Psychiatry SC Psychiatry GA 820QY UT WOS:000294921700003 PM 21916826 ER PT J AU Sharma, GVRK Woods, PA Lindsey, N O'Connell, C Connolly, L Joseph, J McIntyre, KM AF Sharma, G. V. R. K. Woods, Patricia A. Lindsey, Nancy O'Connell, Carol Connolly, Louise Joseph, Jacob McIntyre, Kevin M. TI Noninvasive Monitoring of Left Ventricular End-Diastolic Pressure Reduces Rehospitalization Rates in Patients Hospitalized for Heart Failure: A Randomized Controlled Trial SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Valsalva maneuver; left ventricular end-diastolic pressure; heart failure; outcomes; hospitalization ID ARTERY CATHETERIZATION EFFECTIVENESS; ESCAPE TRIAL; MANAGEMENT; HEMODYNAMICS; SYSTEM AB Background: In patients admitted for heart failure (HF), unrecognized elevation of left ventricular end-diastolic pressure (LVEDP) at the time of discharge may have a role in the high rehospitalization rate for HF on follow-up. Methods and Results: In a small, prospective study (n = 50), patients admitted for HF were randomized to management guided by daily noninvasive estimated LVEDP monitoring (Group I, open) to a target LVEDP of <20 mm Hg or management based on clinical assessment alone without knowledge of the estimated LVEDP (Group II, blinded). Noninvasive estimated LVEDP was measured by the VeriCor monitor, which uses the Valsalva maneuver to derive the LVEDP. The primary endpoints were the reduction of estimated LVEDP at discharge and the HF rehospitalization rate on follow-up. Estimated LVEDP was significantly reduced at discharge in the open group compared with the blinded group (mean estimated LVEDP 19.7 +/- 1.3 mm Hg vs 25.6 +/- 1.5 mm Hg, respectively, P = 0.01). The rehospitalization rates for HF on follow-up were significantly improved in the open group compared with the blinded group (at 1 month: 0% vs 25%, respectively [P = .05]; at 3 months: 0% vs 32% [P = .01]; at 6 months: 4% vs 36% [P = .01]; at 1 year: 16% vs 48% [P = .03]). Conclusions: When HF is managed by clinical assessment only, estimated LVEDPs remain high at discharge, resulting in early and frequent rehospitalization for HF. Therapy guided by estimated LVEDP monitoring optimizes filling pressures and reduces HF rehospitalization rates. (J Cardiac Fail 2011;17:718-725) C1 [Sharma, G. V. R. K.; Woods, Patricia A.; Lindsey, Nancy; O'Connell, Carol; Connolly, Louise; Joseph, Jacob] VA Boston Healthcare Syst, Boston, MA USA. [Sharma, G. V. R. K.; Joseph, Jacob] Harvard Univ, Sch Med, Boston, MA USA. [McIntyre, Kevin M.] CVP Diagnost, Boston, MA USA. RP Sharma, GVRK (reprint author), Vet Adm Boston Healthcare Syst, Dept Cardiol, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM gvrk_sharma@hotmail.com FU CVP Diagnostics FX Funding: CVP Diagnostics. NR 23 TC 12 Z9 13 U1 0 U2 3 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 SEP PY 2011 VL 17 IS 9 BP 718 EP 725 DI 10.1016/j.cardfail.2011.04.014 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 821NB UT WOS:000294980600004 PM 21872140 ER PT J AU Manzano-Fernandez, S Pastor-Perez, FJ Barquero-Perez, O Pascual-Figal, DA Goya-Esteban, R Rojo-Alvarez, JL Caamano-Fernandez, A Martinez-Espejo, MDM Januzzi, JL Valdes, M Garcia-Alberola, A AF Manzano-Fernandez, Sergio Pastor-Perez, Francisco J. Barquero-Perez, Oscar Pascual-Figal, Domingo A. Goya-Esteban, Rebeca Luis Rojo-Alvarez, Jose Caamano-Fernandez, Antonio Martinez Martinez-Espejo, Maria Dolores Januzzi, James Louis Valdes, Mariano Garcia-Alberola, Arcadio TI Short-Term Variability of Heart Rate Turbulence in Chronic Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Holter monitoring; heart failure; heart rate turbulence; variability ID ACUTE MYOCARDIAL-INFARCTION; VENTRICULAR PREMATURE BEATS; DILATED CARDIOMYOPATHY; RISK STRATIFICATION; EUROPEAN-SOCIETY; MORTALITY; GUIDELINES; ASSOCIATION; RELIABILITY; PREDICTOR AB Background: Heart rate turbulence (HRT) is associated with risk in chronic heart failure (CHF). The objective of this study was to assess the short-term variability of HRT and to compare the diagnostic yield of 7-day (7DH) versus 24-hour (1DH) Hotter monitoring for calculating HRT in a CHF population. Methods and Results: Forty-nine consecutive patients with CHF were studied. At inclusion, 7DH was performed to evaluate the variability of HRT parameters. For categorized analyses, turbulence onset (TO) >= 0% and turbulence slope (TS) <= 2.5 ms/RR were defined as abnormal, and patients were classified into subgroups based on the number of abnormal HRT parameters. The cumulative percentage of patients with calculable HRT increased from 69.4% with 1DH to 93.9% with 7DH. The intraclass correlation co-efficients across the 7-day monitoring were 0.81 (95% confidence interval [CI] 0.70-0.89) for TO and 0.90 (95% CI 0.84-0.95) for TS. When comparing 2 randomly selected days, TO and TS values were similar (P > .1) and showed a strong correlation (TO: r = 0.79; TS: r = 0.84: P < .001). Bland-Altman plots showed a mean difference of 0.31% (95% CI -0.07 to 0.70) for TO and 0.44 ms/RR (95% CI -1.37 to 0.48) for TS. In contrast, categorized analyses showed that up to 16% of patients changed their HRT subgroup score from day 1 to day 2 of comparison. Conclusions: In this population, 7DH significantly increased the percentage of patients with calculable HRT parameters. The short-term variability of the quantitative HRT values was good, but when patients were categorized into the established HRT subgroups, the concordance was suboptimal. (J Cardiac Fail 2011;17:735-741) C1 [Manzano-Fernandez, Sergio; Pastor-Perez, Francisco J.; Pascual-Figal, Domingo A.; Martinez Martinez-Espejo, Maria Dolores; Valdes, Mariano; Garcia-Alberola, Arcadio] Univ Hosp Virgen de la Arrixaca, Dept Cardiol, Murcia, Spain. [Barquero-Perez, Oscar; Goya-Esteban, Rebeca; Luis Rojo-Alvarez, Jose; Caamano-Fernandez, Antonio] Univ Rey Juan Carlos, Dept Signal Theory & Commun, Madrid, Spain. [Januzzi, James Louis] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Manzano-Fernandez, S (reprint author), Univ Hosp Virgen de la Arrixaca, Dept Cardiol, Murcia, Spain. EM sergiosmf13@hotmail.com RI Pascual Figal, Domingo /B-3794-2008; Goya-Esteban, Rebeca/C-6409-2013; Barquero-Perez, Oscar/C-6425-2013; Caamano, Antonio/C-8631-2011 OI Pascual Figal, Domingo /0000-0002-4993-9540; Caamano, Antonio/0000-0001-6532-5314 FU Spanish Government [TEC2009-12098, TEC2010-19263]; Ministerio de Educacion (Spanish Government) [AP2009-1726] FX Funding: Research Project from Medtronic Iberica and Research Grants TEC2009-12098 and TEC2010-19263 from the Spanish Government.; Oscar Barquero-Perez has the support of a FPU grant (reference number AP2009-1726) from the Ministerio de Educacion (Spanish Government). NR 24 TC 5 Z9 7 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 SEP PY 2011 VL 17 IS 9 BP 735 EP 741 DI 10.1016/j.cardfail.2011.05.007 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 821NB UT WOS:000294980600007 PM 21872143 ER PT J AU Sengel, C Gavarini, S Sharma, N Ozelius, LJ Bragg, DC AF Sengel, Cem Gavarini, Sophie Sharma, Nutan Ozelius, Laurie J. Bragg, D. Cristopher TI Dimerization of the DYT6 dystonia protein, THAP1, requires residues within the coiled-coil domain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dimerization; dystonia; DYT6; leucine zipper; THAP1 ID NUCLEAR-LOCALIZATION SIGNAL; PRIMARY TORSION DYSTONIA; EARLY-ONSET DYSTONIA; DNA-BINDING; LEUCINE-ZIPPER; AMINO-ACID; IMPORTIN-ALPHA; ZINC-FINGER; SEQUENCE VARIANTS; MUTANT TORSINA AB Thanatos-associated [THAP] domain-containing apoptosis-associated protein 1 (THAP1) is a DNA-binding protein that has been recently associated with DYT6 dystonia, a hereditary movement disorder involving sustained, involuntary muscle contractions. A large number of dystonia-related mutations have been identified in THAP1 in diverse patient populations worldwide. Previous reports have suggested that THAP1 oligomerizes with itself via a C-terminal coiled-coil domain, raising the possibility that DYT6 mutations in this region might affect this interaction. In this study, we examined the ability of wild-type THAP1 to bind itself and the effects on this interaction of the following disease mutations: C54Y, F81L, Delta F132, T142A, I149T, Q154fs180X, and A166T. The results confirmed that wild-type THAP1 associated with itself and most of the DYT6 mutants tested, except for the Q154fs180X variant, which loses most of the coiled-coil do-main because of a frameshift at position 154. However, deletion of C-terminal residues after position 166 produced a truncated variant of THAP1 that was able to bind the wild-type protein. The interaction of THAP1 with itself therefore required residues within a 13-amino acid region (aa 154-166) of the coiled-coil domain. Further inspection of this sequence revealed elements highly consistent with previous descriptions of leucine zippers, which serve as dimerization domains in other transcription factor families. Based on this similarity, a structural model was generated to predict how hydrophobic residues in this region may mediate dimerization. These observations offer additional insight into the role of the coiled-coil domain in THAP1, which may facilitate future analyses of DYT6 mutations in this region. C1 [Sengel, Cem; Sharma, Nutan; Bragg, D. Cristopher] Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Charlestown, MA 02129 USA. [Gavarini, Sophie; Ozelius, Laurie J.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Ozelius, Laurie J.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. RP Bragg, DC (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM bragg@helix.mgh.harvard.edu FU NIH [P30NS045776, NS064450, NS069973, NS071025, RR026123, NS037409]; Benign Essential Blepharospasm Research Foundation; Tyler's Hope for a Dystonia Cure, Inc. FX We gratefully acknowledge Dr John R. Engen for advice on structural modeling of THAP1, Mr Igor Bagayev and the MGH Neuroscience Center Image and Analysis Core (supported by NIH P30NS045776) for use of the Nikon scanner; and Ms Suzanne McDavitt for skilled editorial assistance in the preparation of the manuscript. Support for this work was provided by: NIH NS064450 (DCB), NS069973 (DCB), NS071025 (DCB), RR026123 (LJO), and NS037409 (LJO, NS); the Benign Essential Blepharospasm Research Foundation (DCB); and Tyler's Hope for a Dystonia Cure, Inc. (DCB). The authors declare no financial conflicts of interest. NR 86 TC 12 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2011 VL 118 IS 6 BP 1087 EP 1100 DI 10.1111/j.1471-4159.2011.07386.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 820JB UT WOS:000294900600014 PM 21752024 ER PT J AU Mannix, RC Zhang, J Park, J Lee, C Whalen, MJ AF Mannix, Rebekah C. Zhang, Jimmy Park, Juyeon Lee, Christopher Whalen, Michael J. TI Detrimental Effect of Genetic Inhibition of B-Site App-Cleaving Enzyme 1 on Functional Outcome after Controlled Cortical Impact in Young Adult Mice SO JOURNAL OF NEUROTRAUMA LA English DT Article DE beta-amyloid; traumatic brain injury ID TRAUMATIC BRAIN-INJURY; AMYLOID PROTEIN DEPOSITION; ALZHEIMERS-DISEASE; HEAD-INJURY; BETA-SECRETASE; RISK FACTOR; WATER-MAZE; AGE; NEURONS; ASSOCIATION AB beta-Amyloid (A beta) peptides, most notably associated with Alzheimer's disease, have been implicated in the pathogenesis of secondary injury after traumatic brain injury (TBI). A prior study has demonstrated that blocking the beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (Bace1) required for production of A beta from APP improved functional and histologic outcomes after controlled cortical impact (CCI) in aged mice. However, the majority of patients with severe TBI are young adults under the age of 40. Prior experimental models have suggested age-dependent differences in A beta clearance, and a recent study in our lab suggests that young animals remediate acute elevations in A beta after CCI better than older animals. We therefore tested the hypothesis that Bace1 deletion in young adult mice would not be protective after CCI. Male Bace1 knockout (Bace1(-/-)) and wild-type Bace1(+/+) (C57BL/6) mice (2-3 months old) were subjected to CCI (n=18-23/group) or sham injury (n=10-12/group). Functional outcomes were assessed with wire grip (motor) and the Morris water maze (MWM; spatial memory). Soluble A beta levels were assessed at 48 h after CCI. Histopathological outcomes were assessed by lesion and hippocampal volume. Clustered ordinal logistic regression showed overall significant impairment in motor performance in injured Bace1(-/-) versus Bace1(+/+) animals (p=0.003). No significant differences in MWM performance were found on repeated-measures ANOVA (p=0.11) between groups. Probe scores were significantly worse in injured Bace1(-/-) versus Bace1(+/+) mice (p=0.0009). Soluble A beta(40) was significantly lower in ipsilateral hemispheres of Bace1(-/-) than in Bace1(+/+) animals after CCI (0.9 [IQR 0.88-0.94] pmol/g protein versus 3.8 [IQR 2.4-6.0] pmol/g protein; p=0.005). Lesion and hippocampal volumes did not differ between injured groups. The data suggest that therapies targeting Bace1 may need to be tailored according to age and injury severity, as their use may exacerbate functional deficits after TBI in younger or less severely injured patients. C1 [Mannix, Rebekah C.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Emergency Med,Dept Med, Boston, MA 02115 USA. [Mannix, Rebekah C.; Zhang, Jimmy; Park, Juyeon; Lee, Christopher; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. [Zhang, Jimmy; Park, Juyeon; Lee, Christopher; Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA. RP Mannix, RC (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Emergency Med,Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM Rebekah.Mannix@childrens.harvard.edu FU National Institute of Child Health & Human Development [5K12HD052896]; Charles Hood Foundation; National Institute of Neurological Disorders and Stroke [5RO1NS047447] FX This work was supported by grants from the National Institute of Child Health & Human Development 5K12HD052896 (R.C.M.), the Charles Hood Foundation (R.C.M.), and the National Institute of Neurological Disorders and Stroke 5RO1NS047447 (M.J.W.). NR 38 TC 13 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP PY 2011 VL 28 IS 9 BP 1855 EP 1861 DI 10.1089/neu.2011.1759 PG 7 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 821AK UT WOS:000294947000016 PM 21639727 ER PT J AU Holschneider, DP Guo, YM Roch, M Norman, KM Scremin, OU AF Holschneider, Daniel P. Guo, Yumei Roch, Margareth Norman, Keith M. Scremin, Oscar U. TI Acetylcholinesterase Inhibition and Locomotor Function after Motor-Sensory Cortex Impact Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE acetylcholinesterase; cholinergic; motor function; neurorehabilitation; TBI ID TRAUMATIC BRAIN-INJURY; ORAL PHYSOSTIGMINE; MEMORY DEFICITS; WORKING MEMORY; HEAD-INJURY; LONG-TERM; RECOVERY; RATS; RIVASTIGMINE; DONEPEZIL AB Traumatic brain injury (TBI) induces transient or persistent dysfunction of gait and balance. Enhancement of cholinergic transmission has been reported to accelerate recovery of cognitive function after TBI, but the effects of this intervention on locomotor activity remain largely unexplored. The hypothesis that enhancement of cholinergic function by inhibition of acetylcholinesterase (AChE) improves locomotion following TBI was tested in Sprague-Dawley male rats after a unilateral controlled cortical impact (CCI) injury of the motor-sensory cortex. Locomotion was tested by time to fall on the constant speed and accelerating Rotarod, placement errors and time to cross while walking through a horizontal ladder, activity monitoring in the home cages, and rearing behavior. Assessments were performed the 1st and 2nd day and the 1st, 2nd, and 3rd week after TBI. The AChE inhibitor physostigmine hemisulfate (PHY) was administered continuously via osmotic minipumps implanted subcutaneously at the rates of 1.6-12.8 mu mol/kg/day. All measures of locomotion were impaired by TBI and recovered to initial levels between 1 and 3 weeks post-TBI, with the exception of the maximum speed achievable on the accelerating Rotarod, as well as rearing in the open field. PHY improved performance in the accelerating Rotarod at 1.6 and 3.2 mu mol/kg/day (AChE activity 95 and 78% of control, respectively), however, higher doses induced progressive deterioration. No effect or worsening of outcomes was observed at all PHY doses for home cage activity, rearing, and horizontal ladder walking. Potential benefits of cholinesterase inhibition on locomotor function have to be weighed against the evidence of the narrow range of useful doses. C1 [Holschneider, Daniel P.; Guo, Yumei] Univ So Calif, USC Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Univ So Calif, USC Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Univ So Calif, USC Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.; Roch, Margareth; Norman, Keith M.; Scremin, Oscar U.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Scremin, Oscar U.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. RP Holschneider, DP (reprint author), Univ So Calif, USC Keck Sch Med, Dept Psychiat & Behav Sci, 1333 San Pablo St,BMT 403,MC9112, Los Angeles, CA 90033 USA. EM holschne@usc.edu FU Department of Veterans Affairs Rehabilitation Research & Development Merit Review (VA RRD) [B5089R] FX This work was supported by a Department of Veterans Affairs Rehabilitation Research & Development Merit Review (VA RR&D) #B5089R and a VA RR&D Research Career Scientist award (O.U.S). NR 42 TC 11 Z9 11 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD SEP PY 2011 VL 28 IS 9 BP 1909 EP 1919 DI 10.1089/neu.2011.1978 PG 11 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 821AK UT WOS:000294947000020 PM 21787180 ER PT J AU Winkelman, WD Lauderdale, K Balboni, MJ Phelps, AC Peteet, JR Block, SD Kachnic, LA VanderWeele, TJ Balboni, TA AF Winkelman, William D. Lauderdale, Katharine Balboni, Michael J. Phelps, Andrea C. Peteet, John R. Block, Susan D. Kachnic, Lisa A. VanderWeele, Tyler J. Balboni, Tracy A. TI The Relationship of Spiritual Concerns to the Quality of Life of Advanced Cancer Patients: Preliminary Findings SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PALLIATIVE CARE; QUESTIONNAIRE; ILL; ATTITUDES; VALIDITY; BELIEFS; NEEDS AB Purpose: Religion and/or spirituality (R/S) have increasingly been recognized as key elements in patients' experience of advanced illness. This study examines the relationship of spiritual concerns (SCs) to quality of life (QOL) in patients with advanced cancer. Patients and Methods: Patients were recruited between March 3, 2006 and April 14, 2008 as part of a survey-based study of 69 cancer patients receiving palliative radiotherapy. Sixteen SCs were assessed, including 11 items assessing spiritual struggles (e. g., feeling abandoned by God) and 5 items assessing spiritual seeking (e. g., seeking forgiveness, thinking about what gives meaning in life). The relationship of SCs to patient QOL domains was examined using univariable and multivariable regression analysis. Results: Most patients (86%) endorsed one or more SCs, with a median of 4 per patient. Younger age was associated with a greater burden of SCs (beta = -0.01, p = 0.006). Total spiritual struggles, spiritual seeking, and SCs were each associated with worse psychological QOL (beta = -1.11, p = 0.01; beta = -1.67, p < 0.05; and beta = -1.06, p < 0.001). One of the most common forms of spiritual seeking (endorsed by 54%)-thinking about what gives meaning to life-was associated with worse psychological and overall QOL (beta = -5.75, p = 0.02; beta = -12.94, p = 0.02). Most patients (86%) believed it was important for health care professionals to consider patient SCs within the medical setting. Conclusions: SCs are associated with poorer QOL among advanced cancer patients. Furthermore, most patients view attention to SCs as an important part of medical care. These findings underscore the important role of spiritual care in palliative cancer management. C1 [Balboni, Michael J.; Phelps, Andrea C.; Peteet, John R.; Block, Susan D.; Balboni, Tracy A.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 01225 USA. [Peteet, John R.; Block, Susan D.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Lauderdale, Katharine] Harvard Univ, Dept Stat, Boston, MA 02115 USA. [Balboni, Michael J.; Phelps, Andrea C.; Peteet, John R.; Block, Susan D.; Balboni, Tracy A.] Dana Farber Canc Inst, Dept Psychooncol & Palliat Care, Boston, MA 01225 USA. [Kachnic, Lisa A.] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [VanderWeele, Tyler J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 01225 USA. RP Balboni, TA (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 44 Binney St, Boston, MA 01225 USA. EM tbalboni@lroc.harvard.edu FU American Society of Clinical Oncology FX This research was supported in part by an American Society of Clinical Oncology Young Investigator Award to Dr. Tracy Balboni. NR 25 TC 27 Z9 27 U1 1 U2 12 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 SEP PY 2011 VL 14 IS 9 BP 1022 EP 1028 DI 10.1089/jpm.2010.0536 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 819CU UT WOS:000294803800010 PM 21767165 ER PT J AU Billings, JA Block, SD AF Billings, J. Andrew Block, Susan D. TI Part III: A Guide for Structured Discussions SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID INTENSIVE-CARE-UNIT; OF-LIFE CARE; SURROGATE DECISION-MAKERS; CHRONIC CRITICAL ILLNESS; TERMINALLY-ILL PATIENTS; FAMILY CONFERENCES; PALLIATIVE CARE; CRITICALLY-ILL; PROACTIVE APPROACH; CLINICAL-PRACTICE C1 [Billings, J. Andrew; Block, Susan D.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Block, Susan D.] Dana Farber Canc Ctr, Dept Psychosocial Oncol & Palliat Care, Boston, MA USA. [Block, Susan D.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Billings, JA (reprint author), 11 1-2 Hilliard St, Cambridge, MA 02138 USA. EM jbillings@partners.org FU Promoting Excellence in End-of-Life Care, a national office of the Robert Wood Johnson Foundation Robert Wood Johnson Foundation FX Susan Block provided helpful suggestions. This research was supported in part by Promoting Excellence in End-of-Life Care, a national office of the Robert Wood Johnson Foundation Robert Wood Johnson Foundation. NR 44 TC 15 Z9 15 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD SEP PY 2011 VL 14 IS 9 BP 1058 EP 1064 DI 10.1089/jpm.2011.0038-c PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 819CU UT WOS:000294803800015 PM 21910613 ER PT J AU Wheelwright, D Vesel, T Scarlett, WG AF Wheelwright, Divna Vesel, Tamara Scarlett, W. George TI For Xavier SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 [Vesel, Tamara] Harvard Univ, Dana Farber Canc Inst, Pediat Palliat Div, Dept Palliat Care & Psychosocial Oncol, Boston, MA 02115 USA. [Vesel, Tamara] Harvard Univ, Childrens Hosp, Boston, MA 02115 USA. [Wheelwright, Divna; Scarlett, W. George] Tufts Univ, Eliot Pearson Dept Child Dev, Boston, MA 02111 USA. RP Vesel, T (reprint author), Harvard Univ, Dana Farber Canc Inst, Pediat Palliat Div, Dept Palliat Care & Psychosocial Oncol, Boston, MA 02115 USA. EM Tamara_Vesel@dfci.harvard.edu 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 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD SEP PY 2011 VL 14 IS 9 BP 1068 EP 1068 DI 10.1089/jpm.2011.0049 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 819CU UT WOS:000294803800018 PM 21910616 ER PT J AU Niederman, R AF Niederman, Richard TI MORE ABOUT EVIDENCE-BASED DENTISTRY Response SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Letter C1 Forsyth Inst, Ctr Evidence Based Dent, Boston, MA 02115 USA. RP Niederman, R (reprint author), Forsyth Inst, Ctr Evidence Based Dent, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2011 VL 142 IS 9 BP 1003 EP 1004 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 821KD UT WOS:000294973000006 ER PT J AU Terrando, N Brzezinski, M Degos, V Eriksson, LI Kramer, JH Leung, JM Miller, BL Seeley, WW Vacas, S Weiner, MW Yaffe, K Young, WL Xie, ZC Maze, M AF Terrando, Niccolo Brzezinski, Marek Degos, Vincent Eriksson, Lars I. Kramer, Joel H. Leung, Jacqueline M. Miller, Bruce L. Seeley, William W. Vacas, Susana Weiner, Michael W. Yaffe, Kristine Young, William L. Xie, Zhongcong Maze, Mervyn TI Perioperative Cognitive Decline in the Aging Population SO MAYO CLINIC PROCEEDINGS LA English DT Article ID INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; ISOFLURANE INDUCES APOPTOSIS; BILATERAL FEMUR FRACTURE; CORONARY-ARTERY-BYPASS; AMYLOID PROTEIN-LEVELS; POSTOPERATIVE DELIRIUM; ALZHEIMERS-DISEASE; NONCARDIAC SURGERY; RISK-FACTORS AB Elderly patients who have an acute Illness or who undergo surgery often experience cognitive decline. The pathophysiologic mechanisms that cause neurodegeneration resulting in cognitive decline, including protein deposition and neuroInflammation, also play a role in animal models of surgery-Induced cognitive decline. With the aging of the population, surgical candidates of advanced age with underlying neurodegeneration are encountered more often, raising concerns that, in patients with this combination, cognitive function will precipitously decline postoperatively. This special article is based on a symposium that the University of California, San Francisco, convened to explore the contributions of surgery and anesthesia to the development of cognitive decline In the aged patient. A road map to further elucidate the mechanisms, diagnosis, risk factors, mitigation, and treatment of postoperative cognitive decline in the elderly is provided. C1 [Terrando, Niccolo; Brzezinski, Marek; Degos, Vincent; Eriksson, Lars I.; Leung, Jacqueline M.; Vacas, Susana; Young, William L.; Maze, Mervyn] Univ Calif San Francisco, Sch Med, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Degos, Vincent; Young, William L.] Univ Calif San Francisco, Sch Med, Cerebrovasc Res Ctr, San Francisco, CA 94143 USA. [Kramer, Joel H.; Miller, Bruce L.; Seeley, William W.; Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Sch Med, Dept Radiol & Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Eriksson, Lars I.] Karolinska Inst, Dept Physiol & Pharmacol, Sect Anesthesiol & Intens Care Med, Stockholm, Sweden. [Vacas, Susana] Programme Adv Med Educ, Lisbon, Portugal. [Weiner, Michael W.] DVA Med Ctr, MRS Unit, San Francisco, CA USA. [Xie, Zhongcong] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Maze, M (reprint author), Univ Calif San Francisco, Sch Med, Dept Anesthesia & Perioperat Care, 521 Parnassus Ave,C455, San Francisco, CA 94143 USA. EM mazem@anesthesia.ucsf.edu RI Vacas, Susana/J-3123-2014 OI Vacas, Susana/0000-0002-4099-3946 FU Elan/Wyeth Alzheimer's Immunotherapy Program North American Advisory Board; Novartis; Alzheimer's Association, Forest, University of California; University Medical School; Colloquium Paris; Ipsen; Wenner-Gren Foundations; Social Security Administration; Korean Neurological Association; National Institutes of Health; Washington University at St. Louis; Banner Alzheimer's Institute; Veterans Affairs Central Office, Beijing Institute of Geriatrics, Innogenetics; New York University; Neuro Vigil, Inc; CHRU-Hopital Roger Salengro; Siemens; AstraZeneca; Geneva University Hospitals; Lilly; University of California; San Diego-ADNI; Paris University; Institut Catala de Neurosciencies Aplicades; University of New Mexico School of Medicine; Pfizer; NIA FX Dr Weiner reports the following financial disclosures: served on the following scientific boards in 2009, Elan/Wyeth Alzheimer's Immunotherapy Program North American Advisory Board, Novartis Misfolded Protein Scientific Advisory Board Meeting, Banner Alzheimer's Institute Alzheimer's Prevention Initiative Advisory Board Meeting, and Research Advisory Committee on Gulf War Veterans' Illnesses; in 2010, Lilly, Araclon and Institut Catala de Neurociencies Aplicades, Gulf War Veterans Illnesses Advisory Committee, VACO, and Biogen Idec; and in 2011, Pfizer. He did consulting for the following in 2009: Elan/Wyeth, Novartis, Forest, Ipsen, and Daiichi Sankyo, Inc; in 2010, Astra Zeneca, Araclon, Medivation/Pfizer, Ipsen, TauRx Therapeutics Ltd, Bayer Healthcare, Biogen Idec, Exonhit Therapeutics, SA, Servier, and Synarc; in 2011, Pfizer. He received funding for travel in 2009 from Elan/Wyeth Alzheimer's Immunotherapy Program North American Advisory Board, Alzheimer's Association, Forest, University of California, Davis, Tel-Aviv University Medical School, Colloquium Paris, Ipsen, Wenner-Gren Foundations, Social Security Administration, Korean Neurological Association, National Institutes of Health, Washington University at St. Louis, Banner Alzheimer's Institute, Clinical Trials on Alzheimer's Disease, Veterans Affairs Central Office, Beijing Institute of Geriatrics, Innogenetics, and New York University; in 2010, Neuro Vigil, Inc, CHRU-Hopital Roger Salengro, Siemens, AstraZeneca, Geneva University Hospitals, Lilly, University of California, San Diego-ADNI, Paris University, Institut Catala de Neurosciencies Aplicades, University of New Mexico School of Medicine, Ipsen, and CTAD (Clinical Trials on Alzheimer's Disease); in 2011, Pfizer, AD PD meeting, Paul Sabatier University, and Novartis. Dr Weiner serves on the Editorial Advisory Board for Alzheimer's & Dementia, and MRI; received honoraria in 2009 from American Academy of Neurology and Ipsen; in 2010, from NeuroVigil, Inc, and Insitut Catala de Neurociencies Aplicades. He receives Commercial Entities Research Support from Merck and Avid; Government Entities Research Support from DOD and VA; and has stock options in Synarc and Elan. The following organizations contribute to the Foundation for NIH and thus to the NIA-funded Alzheimer's Disease Neuroimaging Initiative: Abbott, Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Anonymous Foundation, AstraZeneca, Bayer Healthcare, BioClinica Inc (ADNI 2), Bristol-Myers Squibb, Cure Alzheimer's Fund, Eisai, Elan, Gene Network Sciences, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly & Company, Medpace, Merck, Novartis, Pfizer Inc, Roche, Schering Plough, Synarc, and Wyeth. NR 118 TC 59 Z9 65 U1 3 U2 14 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD SEP PY 2011 VL 86 IS 9 BP 885 EP 893 DI 10.4065/mcp.2011.0332 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 821JC UT WOS:000294970200010 PM 21878601 ER PT J AU Lee, D Desmond, MJ Fraser, SA Katerelos, M Gleich, K Martinello, P Li, YQ Thomas, MC Michelucci, R Cole, AJ Saftig, P Schwake, M Stapleton, D Berkovic, SF Power, DA AF Lee, D. Desmond, M. J. Fraser, S. A. Katerelos, M. Gleich, K. Martinello, P. Li, Y. Q. Thomas, M. C. Michelucci, R. Cole, A. J. Saftig, P. Schwake, M. Stapleton, D. Berkovic, S. F. Power, D. A. TI FAILURE OF PROTEOLYSIS AS A NOVEL MECHANISM FOR TUBULAR PROTEINURIA IN MICE AND HUMANS LACKING THE INTRINSIC LYSOSOMAL PROTEIN SCARB2/LIMP-2 SO NEPHROLOGY LA English DT Meeting Abstract C1 [Lee, D.; Desmond, M. J.; Power, D. A.] Austin Hlth, Dept Nephrol, Melbourne, Vic, Australia. [Martinello, P.] Austin Hlth, Dept Anat Pathol, Melbourne, Vic, Australia. [Fraser, S. A.; Katerelos, M.; Gleich, K.; Li, Y. Q.; Power, D. A.] Austin Hlth, Inst Breathing & Sleep, Melbourne, Vic, Australia. [Thomas, M. C.] Danielle Alberti Mem Ctr Diabet Complicat, Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. [Michelucci, R.] Univ Bologna, Dept Neurosci, Bellaria Hosp, Neurol Unit, Bologna, Italy. [Cole, A. J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. [Saftig, P.; Schwake, M.] Univ Kiel, Inst Biochem, D-24098 Kiel, Germany. [Stapleton, D.] Univ Melbourne, Dept Biochem & Mol Biol, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic, Australia. [Berkovic, S. F.] Austin Hlth, Epilepsy Res Ctr, Melbourne, Vic, Australia. [Berkovic, S. F.; Power, D. A.] Univ Melbourne, Dept Med, Melbourne, Vic, Australia. RI Saftig, Paul/A-7966-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD SEP PY 2011 VL 16 SU 1 MA 074 BP 44 EP 44 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 821LX UT WOS:000294977600075 ER PT J AU Nishino, M Medoff, BD Mark, EJ Matsubara, O O'Donnell, WJ Currier, PF Kradin, RL AF Nishino, Michiya Medoff, Benjamin D. Mark, Eugene J. Matsubara, Osamu O'Donnell, Walter J. Currier, Paul F. Kradin, Richard L. TI Variant alveolar lipoproteinosis: A syndrome with distinct clinical and pathological features SO PATHOLOGY INTERNATIONAL LA English DT Article DE corticosteroid therapy; lung; lung lavage; pulmonary alveolar proteinosis ID COLONY-STIMULATING FACTOR; PERITONEAL-MACROPHAGE FUNCTION; OPEN ABDOMINAL-SURGERY; PREOPERATIVE CORTICOSTEROIDS; DEFICIENT MICE; RAT MODEL; PROTEINOSIS; AUTOANTIBODIES; SIROLIMUS AB Pulmonary alveolar proteinosis (PAP) is a rare condition in which pulmonary macrophages fail to clear surfactant, resulting in the alveolar accumulation of lipoproteinaceous debris. The histopathology of PAP is typified by diffuse filling of terminal airways with eosinophilic, PAS/diastase (PAS/D)-positive acellular material. We present five patients who showed histopathological changes in the lungs consistent with mild PAP. However, these cases were notable for the abundance of degenerating alveolar macrophages, weak PAS staining of lipoproteinaceous material and paucity of lamellated bodies on ultrastructural examination. Only one patient showed the CT finding of mosaiform 'crazy-paving' and the opalescent bronchoalveolar lavage fluid characteristic of PAP. In one case, therapeutic lung lavage based on a presumptive diagnosis of PAP exacerbated respiratory distress. Three patients showed partial or near-complete resolution of disease in response to high-dose corticosteroid therapy, a treatment approach that is generally ineffective in PAP. We conclude that distinguishing 'variant alveolar lipoproteinosis' from classical PAP is clinically important. Despite the otherwise typical appearance of lipoproteinaceous alveolar material in lung biopsies, the presence of degenerating foamy macrophages and atypical histochemical, ultrastructural and radiographic features suggest a steroid-responsive form of proteinosis that is likely pathogenetically distinct and may not be amenable to whole-lung lavage. C1 [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Pathol Serv, Boston, MA 02114 USA. [Medoff, Benjamin D.; O'Donnell, Walter J.; Currier, Paul F.; Kradin, Richard L.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Matsubara, Osamu] Natl Def Med Coll, Dept Basic Pathol, Tokorozawa, Saitama 359, Japan. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Pathol Serv, 55 Fruit St, Boston, MA 02114 USA. EM rkradin@partners.org NR 33 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD SEP PY 2011 VL 61 IS 9 BP 509 EP 517 DI 10.1111/j.1440-1827.2011.02710.x PG 9 WC Pathology SC Pathology GA 821LO UT WOS:000294976700002 PM 21884300 ER PT J AU Cao, XG Shen, DF Patel, MM Tuo, JS Johnson, TM Olsen, TW Chan, CC AF Cao, Xiaoguang Shen, Defen Patel, Mrinali M. Tuo, Jingsheng Johnson, T. Mark Olsen, Timothy W. Chan, Chi-Chao TI Macrophage polarization in the maculae of age-related macular degeneration: A pilot study SO PATHOLOGY INTERNATIONAL LA English DT Article DE age-related macular degeneration (AMD); chemokine; choroidal neovascularization; M1 macrophage; M2 macrophage ID CHOROIDAL NEOVASCULARIZATION; BRUCHS MEMBRANE; ACTIVATION; ANGIOGENESIS; INFLAMMATION; INVOLVEMENT; EXPRESSION; PHENOTYPE; GROWTH; SYSTEM AB Macrophages can be polarized to exhibit either proinflammatory M1 or pro-angiogenic M2 phenotypes, but have high phenotypic plasticity. This pilot study investigated macrophage polarization in the macular retina and choroid of age-related macular degeneration (AMD) and non-AMD subjects, as well as in AMD choroidal neovascular membranes (CNVM). All specimens were evaluated for routine histopathology. Quantitative real-time polymerase chain reaction for representative M1 (CXCL11) and M2 (CCL22) transcripts were performed on macular choroidal trephines (MCT) of 19 AMD and nine non-AMD eye bank eyes, on the microdissected macular retinal cells from the archived slides of five geographic atrophic AMD, five exudative/neovascular AMD, and eight normal autopsied eyes, and on microdissected inflammatory cells from two surgically removed CNVM that did not respond to anti-vascular endothelial growth factor (VEGF) therapy. High M2-chemokine transcript and a low ratio of M1 to M2 chemokine transcript were found in aging non-AMD MCT. Advanced AMD maculae had a higher M1 to M2 chemokine transcript ratio compared to normal autopsied eyes. Macrophages in the two CNVM of patients unresponsive to anti-VEGF therapy were polarized toward either M1 or M2 phenotypes. The number of M2 macrophages was increased compared to M1 macrophages in normal aging eyes. A pathological shift of macrophage polarization may play a potential role in AMD pathogenesis. C1 [Cao, Xiaoguang; Shen, Defen; Patel, Mrinali M.; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Johnson, T. Mark] Natl Retina Inst, Chevy Chase, MD USA. [Patel, Mrinali M.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Olsen, Timothy W.] Emory Univ, Emory Eye Ctr, Atlanta, GA 30322 USA. [Cao, Xiaoguang] Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100871, Peoples R China. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov RI du, zhao jiang/F-6229-2011; OI Tuo, Jingsheng/0000-0002-1372-7810 FU NEI FX The NEI Intramural Research program supported the study. NR 33 TC 72 Z9 78 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1320-5463 J9 PATHOL INT JI Pathol. Int. PD SEP PY 2011 VL 61 IS 9 BP 528 EP 535 DI 10.1111/j.1440-1827.2011.02695.x PG 8 WC Pathology SC Pathology GA 821LO UT WOS:000294976700004 PM 21884302 ER PT J AU Saha, S Beach, MC AF Saha, Somnath Beach, Mary Catherine TI The impact of patient-centered communication on patients' decision making and evaluations of physicians: A randomized study using video vignettes SO PATIENT EDUCATION AND COUNSELING LA English DT Article; Proceedings Paper CT Conference of the European-Association-for-Communication-in-Healthcare (EACH) CY 2010 CL Verona, ITALY SP European Assoc Commun Hlth Care DE Physician-patient relations; Patient-centered care; Communication; Decision making ID PRIMARY-CARE; OUTCOMES; HEALTH; CONSULTATIONS; RELIABILITY; MEDICINE; SCALE; TRUST; MODEL AB Objective: To assess the impact of patient-centered communication (PCC) behaviors on patients' evaluations of physicians and acceptance of clinical recommendations. Methods: We randomized 248 patients to view video-recorded, standardized vignettes, depicting a cardiologist using a high vs. low degree of PCC while recommending bypass surgery to a patient with angina and 3-vessel coronary artery disease. We compared patients' ratings of the physician and their decision making in response to the physician's recommendation, for high vs. low PCC vignettes. Results: Patients viewing high PCC vignettes rated the video physician more favorably overall (3.01 vs. 2.12, p < 0.001) and as more competent (3.22 vs. 2.66, p < 0.001) and trustworthy (2.93 vs. 2.28, p < 0.001) than those viewing the low PCC version (0-4 range for all scales). Patients viewing the high PCC version more frequently said they would undergo bypass surgery (96% vs. 74%, p < 0.001) if they were the patient in the video. Conclusion: Patients expressed greater confidence in physicians who used more PCC behaviors, and greater willingness to accept an evidence-based recommendation. Practice implications: PCC may make physicians more effective in the delivery of evidence-based care. Published by Elsevier Ireland Ltd. C1 [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR 97239 USA. [Saha, Somnath] Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Beach, Mary Catherine] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. RP Saha, S (reprint author), Portland VA Med Ctr, Gen Internal Med Sect, 3710 SW US Vet Hosp Rd P2HSRD, Portland, OR 97239 USA. EM sahas@ohsu.edu FU NIMH NIH HHS [R34 MH089279, R34 MH089279-01A1, R34 MH089279-02]; NIMHD NIH HHS [L60 MD000303, L60 MD000303-01, L60 MD000303-02] NR 33 TC 26 Z9 27 U1 1 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD SEP PY 2011 VL 84 IS 3 SI SI BP 386 EP 392 DI 10.1016/j.pec.2011.04.023 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 820XM UT WOS:000294939400015 PM 21600723 ER PT J AU Mehta, NK Chang, VW AF Mehta, Neil K. Chang, Virginia W. TI Secular Declines in the Association Between Obesity and Mortality in the United States SO POPULATION AND DEVELOPMENT REVIEW LA English DT Article ID BODY-MASS-INDEX; US ADULTS; LIFE EXPECTANCY; RISK-FACTORS; DEATHS; OVERWEIGHT; TRENDS; UNDERWEIGHT; PREVALENCE; SMOKING AB Recent research suggests that rising obesity will restrain future gains in US life expectancy and that obesity is an important contributor to the current shortfall in US longevity compared to other high-income countries. Estimates of the contribution of obesity to current and future national-level mortality patterns are sensitive to estimates of the magnitude of the association between obesity and mortality at the individual level. We assessed secular trends in the obesity/mortality association among cohorts of middle-aged adults between 1948 and 2006 using three long-running US data sources: the Framingham Heart Study, the National Health and Nutrition Examination Survey, and the National Health Interview Survey. We find substantial declines over time in the magnitude of the association between obesity and overall mortality and, in certain instances, cardiovascular-specific mortality. We conclude that estimates of the contribution of obesity to current national-level mortality patterns should take into account recent reductions in the magnitude of the obesity and mortality association. C1 [Mehta, Neil K.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Chang, Virginia W.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Chang, Virginia W.] Univ Penn, Philadelphia, PA 19104 USA. RP Mehta, NK (reprint author), Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. FU NIA NIH HHS [T32 AG000177-19, T32 AG000177] NR 46 TC 31 Z9 31 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0098-7921 J9 POPUL DEV REV JI Popul. Dev. Rev. PD SEP PY 2011 VL 37 IS 3 BP 435 EP + DI 10.1111/j.1728-4457.2011.00429.x PG 18 WC Demography; Sociology SC Demography; Sociology GA 818PB UT WOS:000294764500002 PM 22110257 ER PT J AU Handel, DA Pines, J Aronsky, D Genes, N Ginde, AA Hackman, J Hilton, JA Hwang, U Kamali, M Powell, E Sattarian, M Fu, RW AF Handel, Daniel A. Pines, Jesse Aronsky, Dominik Genes, Nicholas Ginde, Adit A. Hackman, Jeffrey Hilton, Joshua A. Hwang, Ula Kamali, Michael Powell, Emilie Sattarian, Medhi Fu, Rongwei TI Variations in Crowding and Ambulance Diversion in Nine Emergency Departments SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Scientific Assembly of the American-College-of-Emergency-Physicians CY SEP, 2010 CL Las Vegas, NV SP Amer Coll Emergency Phys ID OCCUPANCY RATE; DELAYS AB Objectives: The primary study aim was to examine the variations in crowding when an emergency department (ED) initiates ambulance diversion. Methods: This retrospective, multicenter study included nine geographically disparate EDs. Daily ED operational variables were collected during a 12-month period (January 2009 to December 2009), including total number of ED visits, mean overall length of stay (LOS), number of ED beds, and hours on ambulance diversion. The primary outcome variable was the "ED workload rate," a surrogate marker for daily ED crowding. It was calculated as the total number of daily ED visits multiplied by the overall mean LOS (in hours) and divided by the number of ED beds available for acute treatment in a given day. The primary predictor variables were ambulance diversion, as a dichotomous variable of whether or not an ED went on diversion at least once during a 24-hour period, diversion hour quintiles, and sites. Results: The annual ED census ranged from 43,000 to 101,000 patients. The percentage of days that an ED went on diversion at least once varied from 4.9% to 86.6%. On days with ambulance diversion, the mean ED workload rate varied from 17.1 to 62.1 patient LOS hours per ED bed among sites. The magnitude of variation in ED workload rate was similar on days without ambulance diversion. Differences in ED workload rate varied among sites, ranging from 1.0 to 6.0 patient LOS hours per ED bed. ED workload rate was higher on average on diversion days compared to nondiversion days. The mean difference between diversion and nondiversion was statistically significant for the majority of sites. Conclusions: There was marked variation in ED workload rates and whether or not ambulance diversion occurred during a 24-hour period. This variability in initiating ambulance diversion suggests different or inconsistently applied decision-making criteria for initiating diversion. ACADEMIC EMERGENCY MEDICINE 2011; 18: 941-946 (C) 2011 by the Society for Academic Emergency Medicine C1 [Handel, Daniel A.; Fu, Rongwei] Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, Portland, OR 97201 USA. [Pines, Jesse] George Washington Univ, Sch Med, Dept Emergency Med, Dept Hlth Policy,George Washington Sch Publ Hlth, Washington, DC USA. [Aronsky, Dominik] Vanderbilt Univ, Dept Biomed Informat & Emergency Med, Nashville, TN USA. [Genes, Nicholas; Hwang, Ula] Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. [Ginde, Adit A.] Univ Colorado, Dept Emergency Med, Denver Sch Med, Aurora, CO USA. [Hackman, Jeffrey] Univ Missouri, Truman Med Ctr, Dept Emergency Med, Kansas City, MO 64108 USA. [Hilton, Joshua A.] Univ Penn, Dept Emergency Med, Philadelphia, PA 19104 USA. [Hwang, Ula] James J Peters VAMC, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Kamali, Michael] Univ Rochester, Dept Emergency Med, Rochester, NY USA. [Powell, Emilie] Northwestern Univ, Dept Emergency Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Fu, Rongwei] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Handel, DA (reprint author), Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, Portland, OR 97201 USA. EM handeld@ohsu.edu RI Siry, Bonnie/D-7189-2017; OI Genes, Nicholas/0000-0002-9836-2477 FU NIA NIH HHS [K24 AG022345] NR 24 TC 16 Z9 16 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD SEP PY 2011 VL 18 IS 9 BP 941 EP 946 DI 10.1111/j.1553-2712.2011.01149.x PG 6 WC Emergency Medicine SC Emergency Medicine GA 818OZ UT WOS:000294764200008 PM 21906203 ER PT J AU Rutter, CM Knudsen, AB Pandharipande, PV AF Rutter, Carolyn M. Knudsen, Amy B. Pandharipande, Pari V. TI Computer Disease Simulation Models: Integrating Evidence for Health Policy SO ACADEMIC RADIOLOGY LA English DT Article DE Medical imaging; computer simulation; colonography; computed tomographic ID COST-EFFECTIVENESS ANALYSIS; SECONDARY DATA SOURCES; SERVICES TASK-FORCE; COLORECTAL-CANCER; CT COLONOGRAPHY; TOMOGRAPHIC COLONOGRAPHY; BREAST-CANCER; VIRTUAL COLONOSCOPY; MEDICARE POPULATION; DECISION-ANALYSIS AB Computer disease simulation models are increasingly being used to evaluate and inform health care decisions across medical disciplines. The aim of researchers who develop these models is to integrate and synthesize short-term outcomes and results from multiple sources to predict the long-term clinical outcomes and costs of different health care strategies. Policy makers, in turn, can use the predictions generated by disease models together with other evidence to make decisions related to health care practices and resource utilization. Models are particularly useful when the existing evidence does not yield obvious answers or does not provide answers to the questions of greatest interest, such as questions about the relative cost-effectiveness of different practices. This review focuses on models used to inform decisions about imaging technology, discussing the role of disease models for health policy development and providing a foundation for understanding the basic principles of disease modeling. This manuscript draws from the collective computed tomographic colonography modeling experience, reviewing 10 published investigations of the clinical effectiveness and cost-effectiveness of computed tomographic colonography relative to colonoscopy. The discussion focuses on implications of different modeling assumptions and difficulties that may be encountered when evaluating the quality of models. This underscores the importance of forging stronger collaborations between researchers who develop disease models and radiologists, to ensure that policy-level models accurately represent the experience of everyday clinical practices. C1 [Rutter, Carolyn M.] Grp Hlth Res Inst, Biostat Unit, Seattle, WA 98101 USA. [Rutter, Carolyn M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Knudsen, Amy B.; Pandharipande, Pari V.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Pandharipande, Pari V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Rutter, CM (reprint author), Grp Hlth Res Inst, Biostat Unit, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM rutter.c@ghc.org FU National Cancer Institute (Bethesda, MD) [U01-CA-152959-01, K07CA133097] FX This study was supported by grants U01-CA-152959-01 (C.M.R., A.B.K.) and K07CA133097 (P.V.P.) from the National Cancer Institute (Bethesda, MD). NR 56 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 2011 VL 18 IS 9 BP 1077 EP 1086 DI 10.1016/j.acra.2011.02.004 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 812GJ UT WOS:000294278800004 PM 21435924 ER PT J AU Oriol, NE Hayden, EM Joyal-Mowschenson, J Muret-Wagstaff, S Faux, R Gordon, JA AF Oriol, Nancy E. Hayden, Emily M. Joyal-Mowschenson, Julie Muret-Wagstaff, Sharon Faux, Russell Gordon, James A. TI Using immersive healthcare simulation for physiology education: initial experience in high school, college, and graduate school curricula SO ADVANCES IN PHYSIOLOGY EDUCATION LA English DT Article DE mannequin simulation; technology-enhanced education ID MEDICAL-EDUCATION AB Oriol NE, Hayden EM, Joyal-Mowschenson J, Muret-Wagstaff S, Faux R, Gordon JA. Using immersive healthcare simulation for physiology education: initial experience in high school, college, and graduate school curricula. Adv Physiol Educ 35: 252-259, 2011; doi:10.1152/advan.00043.2011.- In the natural world, learning emerges from the joy of play, experimentation, and inquiry as part of everyday life. However, this kind of informal learning is often difficult to integrate within structured educational curricula. This report describes an educational program that embeds naturalistic learning into formal high school, college, and graduate school science class work. Our experience is based on work with hundreds of high school, college, and graduate students enrolled in traditional science classes in which mannequin simulators were used to teach physiological principles. Specific case scenarios were integrated into the curriculum as problem-solving exercises chosen to accentuate the basic science objectives of the course. This report also highlights the historic and theoretical basis for the use of mannequin simulators as an important physiology education tool and outlines how the authors' experience in healthcare education has been effectively translated to nonclinical student populations. Particular areas of focus include critical-thinking and problem-solving behaviors and student reflections on the impact of the teaching approach. C1 [Oriol, Nancy E.; Hayden, Emily M.; Joyal-Mowschenson, Julie; Gordon, James A.] Harvard Univ, Sch Med, Gilbert Program Med Simulat, Boston, MA 02115 USA. [Oriol, Nancy E.; Muret-Wagstaff, Sharon] Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. [Hayden, Emily M.; Gordon, James A.] Massachusetts Gen Hosp, MGH Learning Lab, Boston, MA 02114 USA. [Hayden, Emily M.; Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Joyal-Mowschenson, Julie] Brookline High Sch, Brookline, MA USA. [Faux, Russell] Davis Sq Res Associates, Somerville, MA USA. RP Oriol, NE (reprint author), Harvard Univ, Sch Med, Gilbert Program Med Simulat, 260 Longwood Ave,Suite 244, Boston, MA 02115 USA. EM nancy_oriol@hms.harvard.edu FU Harvard Medical School; Harvard Integrated Life Sciences; Joseph M. & Thelma Linsey Foundation; Theodore & Evelyn Berenson Charitable Foundation; Carol and Howard Anderson Family Fund; The Boston Foundation; Harvard University FX This work was supported by the Gilbert Program in Medical Simulation at Harvard Medical School, a Harvard University Provost Educational Technology grant, Harvard Integrated Life Sciences, the Joseph M. & Thelma Linsey Foundation, the Theodore & Evelyn Berenson Charitable Foundation, the Carol and Howard Anderson Family Fund, and The Boston Foundation. NR 14 TC 5 Z9 5 U1 2 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1043-4046 J9 ADV PHYSIOL EDUC JI Adv. Physiol. Educ. PD SEP PY 2011 VL 35 IS 3 BP 252 EP 259 PG 8 WC Education, Scientific Disciplines; Physiology SC Education & Educational Research; Physiology GA 818QR UT WOS:000294770000004 PM 21908833 ER PT J AU Smulowitz, PB Lipton, R Wharam, JF Adelman, L Weiner, SG Burke, L Baugh, CW Schuur, JD Liu, SW McGrath, ME Liu, B Sayah, A Burke, MC Pope, JH Landon, BE AF Smulowitz, Peter B. Lipton, Robert Wharam, J. Frank Adelman, Leon Weiner, Scott G. Burke, Laura Baugh, Christopher W. Schuur, Jeremiah D. Liu, Shan W. McGrath, Meghan E. Liu, Bella Sayah, Assaad Burke, Mary C. Pope, J. Hector Landon, Bruce E. TI Emergency Department Utilization After the Implementation of Massachusetts Health Reform SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID HOSPITAL EMERGENCY; REGULAR SOURCE; UNITED-STATES; MEDICAL-CARE; ACCESS; VISITS; IMPACT AB Study objective: Health care reform in Massachusetts improved access to health insurance, but the extent to which reform affected utilization of the emergency department (ED) for conditions potentially amenable to primary care is unclear. Our objective is to determine the relationship between health reform and ED use for low-severity conditions. Methods: We studied ED visits, using a convenience sample of 11 Massachusetts hospitals for identical 9-month periods before and after health care reform legislation was implemented in 2006. Individuals most affected by the health reform law (the uninsured and low-income populations covered by the publicly subsidized insurance products) were compared with individuals unlikely to be affected by the legislation (those with Medicare or private insurance). Our main outcome measure was the rate of overall and low-severity ED visits for the study population and the comparison population during the period before and after health reform implementation. Results: Total visits increased from 424,878 in 2006 to 442,102 in 2008. Low-severity visits among publicly subsidized or uninsured patients decreased from 43.8% to 41.2% of total visits for that group (difference=2.6%; 95% confidence interval [CI] 2.25% to 2.85%), whereas low-severity visits for privately insured and Medicare patients decreased from 35.7% to 34.9% of total visits for that group (difference=0.8%; 95% CI 0.62% to 0.98%), for a difference in differences of 1.8% (95% CI 1.7% to 1.9%). Conclusion: Although overall ED volume continues to increase, Massachusetts health reform was associated with a small but statistically significant decrease in the rate of low-severity visits for those populations most affected by health reform compared with a comparison population of individuals less likely to be affected by the reform. Our findings suggest that access to health insurance is only one of a multitude of factors affecting utilization of the ED. [Ann Emerg Med. 2011;58:225-234.] C1 [Smulowitz, Peter B.; Lipton, Robert; Burke, Laura] Harvard Univ, Dept Emergency Med, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Adelman, Leon] Harvard Univ, Harvard Affiliated Emergency Med Residency, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wharam, J. Frank] Harvard Univ, Dept Populat Med, Sch Med, Boston, MA 02215 USA. [Wharam, J. Frank] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Weiner, Scott G.] Tufts Med Ctr, Dept Emergency Med, Boston, MA USA. [Weiner, Scott G.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Baugh, Christopher W.; Schuur, Jeremiah D.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Liu, Shan W.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Landon, Bruce E.] Harvard Univ, Dept Hlth Care Policy, Sch Med, Boston, MA 02215 USA. [McGrath, Meghan E.] Boston Med Ctr, Dept Emergency Med, Boston, MA USA. [McGrath, Meghan E.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Sayah, Assaad] Cambridge Hlth Alliance, Dept Emergency Med, Cambridge, MA USA. [Burke, Mary C.] Milford Reg Med Ctr, Dept Emergency Med, Worcester, MA USA. [Burke, Mary C.] Univ Massachusetts, Med Ctr, Dept Emergency Med, Worcester, MA USA. [Pope, J. Hector] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. RP Smulowitz, PB (reprint author), Harvard Univ, Dept Emergency Med, Sch Med, Beth Israel Deaconess Med Ctr, 1 Deaconess Rd,WCC 2, Boston, MA 02215 USA. EM psmulowi@bidmc.harvard.edu NR 33 TC 44 Z9 44 U1 1 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2011 VL 58 IS 3 BP 225 EP 234 DI 10.1016/j.annemergmed.2011.02.020 PG 10 WC Emergency Medicine SC Emergency Medicine GA 818KK UT WOS:000294750400003 PM 21570157 ER PT J AU Wen, LS AF Wen, Leana S. TI "Old" SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. RP Wen, LS (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, 75 Francis St,Neville House 236-A, Boston, MA 02114 USA. EM LWen@patners.org NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2011 VL 58 IS 3 BP 305 EP 306 DI 10.1016/j.annemergmed.2010.12.013 PG 2 WC Emergency Medicine SC Emergency Medicine GA 818KK UT WOS:000294750400020 PM 21871235 ER PT J AU Caplan, LR Arenillas, J Cramer, SC Joutel, A Lo, EH Meschia, J Savitz, S Tournier-Lasserve, E AF Caplan, Louis R. Arenillas, Juan Cramer, Steven C. Joutel, Anne Lo, Eng H. Meschia, James Savitz, Sean Tournier-Lasserve, Elizabeth TI Stroke-Related Translational Research SO ARCHIVES OF NEUROLOGY LA English DT Review ID CEREBRAL CAVERNOUS MALFORMATIONS; AUTOSOMAL-DOMINANT ARTERIOPATHY; ACUTE ISCHEMIC-STROKE; ANEURYSMAL SUBARACHNOID HEMORRHAGE; CONSTRAINT-INDUCED MOVEMENT; BDNF VAL66MET POLYMORPHISM; CERVICAL ARTERY DISSECTION; SMALL-VESSEL DISEASE; COLLAGEN-IV A1; COL4A1 MUTATIONS AB Stroke-related translational research is multifaceted. Herein, we highlight genome-wide association studies and genetic studies of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, COL4A1 mutations, and cerebral cavernous malformations; advances in molecular biology and biomarkers; newer brain imaging research; and recovery from stroke emphasizing cell-based and other rehabilitative modalities. Arch Neurol. 2011;68(9):1110-1123. Published online May 9, 2011. doi:10.1001/archneurol.2011.99 C1 [Caplan, Louis R.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Lo, Eng H.] Harvard Univ, Sch Med, Dept Radiol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lo, Eng H.] Harvard Univ, Sch Med, Dept Neurol, Neuroprotect Res Lab,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cramer, Steven C.] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Cramer, Steven C.] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92717 USA. [Meschia, James] Mayo Clin, Jacksonville, FL 32224 USA. [Savitz, Sean] Univ Texas Med Sch, Houston, TX USA. [Arenillas, Juan] Univ Valladolid, Dept Neurol, Univ Hosp, Valladolid, Spain. [Joutel, Anne; Tournier-Lasserve, Elizabeth] Univ Paris, Fac Med, F-75252 Paris, France. [Tournier-Lasserve, Elizabeth] Grp Hosp Lariboisiere Fernand Widal, Genet Lab, Paris, France. RP Caplan, LR (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 330 Brookline Ave,Palmer 127 W Campus, Boston, MA 02215 USA. EM lcaplan@bidmc.harvard.edu FU GlaxoSmithKline; Stem Cell Therapeutics FX Dr Cramer has received grant funding from GlaxoSmithKline and Stem Cell Therapeutics and has been a consultant to GlaxoSmithKline, Stem Cell Therapeutics, Pfizer, Photothera, Allergan, and Asubio. NR 160 TC 8 Z9 9 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2011 VL 68 IS 9 BP 1110 EP 1123 DI 10.1001/archneurol.2011.99 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 817RW UT WOS:000294693200002 PM 21555605 ER PT J AU Bird, TD Yu, CE AF Bird, Thomas D. Yu, Chang-En TI Alois Alzheimer's Case, Auguste D., Did Not Carry the N141I Mutation in PSEN2 Characteristic of Alzheimer Disease in Volga Germans Reply SO ARCHIVES OF NEUROLOGY LA English DT Letter C1 [Bird, Thomas D.; Yu, Chang-En] Univ Washington, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98108 USA. RP Bird, TD (reprint author), Univ Washington, Geriatr Res Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbia Way, Seattle, WA 98108 USA. EM tomnroz@u.washington.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 2011 VL 68 IS 9 BP 1211 EP 1211 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 817RW UT WOS:000294693200024 ER PT J AU Devine, SM Carter, S Soiffer, RJ Pasquini, MC Hari, PN Stein, A Lazarus, HM Linker, C Stadtmauer, EA Alyea, EP Keever-Taylor, CA O'Reilly, RJ AF Devine, Steven M. Carter, Shelly Soiffer, Robert J. Pasquini, Marcelo C. Hari, Parameswaran N. Stein, Anthony Lazarus, Hillard M. Linker, Charles Stadtmauer, Edward A. Alyea, Edwin P., III Keever-Taylor, Carolyn A. O'Reilly, Richard J. TI Low Risk of Chronic Graft-versus-Host Disease and Relapse Associated with T Cell-Depleted Peripheral Blood Stem Cell Transplantation for Acute Myelogenous Leukemia in First Remission: Results of the Blood and Marrow Transplant Clinical Trials Network Protocol 0303 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE AML; GVHD; Prophylaxis; Transplantation ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW; ADULT PATIENTS; HEMATOLOGIC MALIGNANCIES; POSTREMISSION THERAPY; WORKING GROUP; CHRONIC PHASE; ADD-BACK; DONORS; RECIPIENTS AB Graft-versus-host disease (GVHD) is most effectively prevented by ex vivo T cell depletion (TCD) of the allograft, but its role in the treatment of patients undergoing allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) in complete remission (CR) remains unclear. We performed a phase 2 single-arm multicenter study to evaluate the role of TCD in AML patients in CR1 or CR2 up to age 65 years. The primary objective was to achieve a disease-free survival (DFS) rate of > 75% at 6 months post-transplantation. A total of 44 patients with AML in CR1 (n = 37) or CR2 (n = 7) with a median age of 48.5 years (range, 21-59 years) received myeloablative chemotherapy and fractionated total body irradiation (1375 cGy) followed by immunomagnetically selected CD34-enriched, T cell depleted allografts from HLA-identical siblings. No pharmacologic GVHD prophylaxis was given. All patients engrafted. The incidence of acute GVHD grade II-IV was 22.7%, and the incidence of extensive chronic GVHD was 6.8% at 24 months. The relapse rate for patients in CR1 was 17.4% at 36 months. With a median follow-up of 34 months, DFS for all patients was 82% at 6 months, and DFS for patients in CR I was 72.8% at 12 months and 58% at 36 months. HCT after myeloablative chemoradiotherapy can be performed in a multicenter setting using a uniform method of TCD, resulting in a low risk of extensive chronic GVHD and relapse for patients with AML in CR1. Biol Blood Marrow Transplant 17: 1343-1351 (2011) (C) 2011 American Society fix Blood and Marrow Transplantation C1 [Devine, Steven M.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA. [Carter, Shelly] EMMES Corp, Rockville, MD USA. [Soiffer, Robert J.; Alyea, Edwin P., III] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pasquini, Marcelo C.; Hari, Parameswaran N.; Keever-Taylor, Carolyn A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Stein, Anthony] City Hope Natl Med Ctr, Duarte, CA USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Linker, Charles] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Stadtmauer, Edward A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [O'Reilly, Richard J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Devine, SM (reprint author), B316 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM steven.devine@osumc.edu FU National Heart, Lung, and Blood Institute; National Cancer Institute; Miltenyi Biotec FX This work was supported in part by the National Heart, Lung, and Blood Institute and the National Cancer Institute, along with contributions from Miltenyi Biotec. NR 40 TC 55 Z9 55 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD SEP PY 2011 VL 17 IS 9 BP 1343 EP 1351 DI 10.1016/j.bbmt.2011.02.002 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 816JQ UT WOS:000294594900010 PM 21320619 ER PT J AU Ojha, RP Evans, EL Felini, MJ Singh, KP Thertulien, R AF Ojha, Rohit P. Evans, Eva L. Felini, Martha J. Singh, Karan P. Thertulien, Raymond TI The association between renal cell carcinoma and multiple myeloma: insights from population-based data SO BJU INTERNATIONAL LA English DT Article DE renal cell carcinoma; multiple myeloma; second primary malignancy; risk factors ID OF-THE-LITERATURE; CASE SERIES; PRIMARY MALIGNANCIES; PRIMARY CANCERS; ADIPOSE-TISSUE; PROLIFERATION; EXPERIENCE; LYMPHOMA; RISK AB OBJECTIVE To evaluate the hypothesis of an association between renal cell carcinoma and multiple myeloma. PATIENTS AND METHODS Data from nine population-based registries in the Surveillance, Epidemiology and End Results programme were used to evaluate two separate cohorts of patients diagnosed between 1973 and 2006: patients diagnosed with renal cell carcinoma as a primary malignancy (n = 57 190) and patients diagnosed with multiple myeloma as a primary malignancy (n = 34 156). We estimated standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs) by dividing the number of observed cases of multiple myeloma within the renal cell carcinoma cohort and the number of renal cell carcinoma cases within the multiple myeloma cohort by the number of expected cases for each malignancy in the US general population. RESULTS The renal cell carcinoma cohort yielded 88 multiple myeloma cases during 293 511 person-years of follow up. Patients with renal cell carcinoma had a higher relative risk of multiple myeloma than the general population (SIR = 1.51, 95% CI 1.21-1.85). The multiple myeloma cohort yielded 69 renal cell carcinoma cases during 100 804 person-years of follow up. Patients with multiple myeloma had a higher relative risk of renal cell carcinoma than the general population (SIR = 1.89, 95% CI 1.47-2.40). CONCLUSION Our analyses revealed a bidirectional association between renal cell carcinoma and multiple myeloma, which typically indicates shared risk factors. C1 [Ojha, Rohit P.] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Ojha, Rohit P.; Evans, Eva L.; Felini, Martha J.] Univ N Texas, Hlth Sci Ctr, Dept Epidemiol, Ft Worth, TX USA. [Singh, Karan P.] Univ N Texas, Hlth Sci Ctr, Dept Biostat, Ft Worth, TX USA. [Thertulien, Raymond] US Oncol, Canc Ctr N Carolina, Asheville, NC USA. RP Ojha, RP (reprint author), 44 Binney St,SM 271, Boston, MA 02115 USA. EM rohit_ojha@dfci.harvard.edu OI Ojha, Rohit/0000-0003-0595-8990 NR 32 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD SEP PY 2011 VL 108 IS 6 BP 825 EP 830 DI 10.1111/j.1464-410X.2010.09892.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 819VZ UT WOS:000294862000009 PM 21091979 ER PT J AU Richardson, PG Lonial, S Jakubowiak, AJ Harousseau, JL Anderson, KC AF Richardson, Paul G. Lonial, Sagar Jakubowiak, Andrzej J. Harousseau, Jean-Luc Anderson, Kenneth C. TI Monoclonal antibodies in the treatment of multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE multiple myeloma; monoclonal antibodies; novel therapies; novel targets; targeted therapies ID CLINICAL-IMPLICATIONS; PHASE-2 TRIAL; IN-VITRO; CELLS; CYTOTOXICITY; THERAPY; CANCER; DEXAMETHASONE; TARGET; INTERLEUKIN-6 AB Despite recent advances in treatment that have significantly improved overall survival, multiple myeloma (MM) remains incurable. Although rituximab, the first monoclonal antibody (MAb) evaluated in MM treatment, provided only very limited benefit, research is ongoing into a number of other MAbs directed against a variety of MM-related target antigens. Given the inherent immune dysfunction associated with MM, newer strategies that may enhance immune function in conjunction with antibodies may also provide a more fruitful clinical approach. Potential MAb targets in MM include growth factors and their receptors, other signalling molecules, and antigens expressed exclusively or predominantly on MM cells. MAb therapy involves a range of mechanisms, including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, interference with receptor-ligand interactions, and MAb conjugation to radioisotopes or toxins. The antigens currently targeted in MM therapy are discussed, along with the development status of the corresponding MAb therapeutics. Elotuzumab, an anti-CS1 MAb, has recently achieved clinically meaningful responses when combined with lenalidomide or bortezomib in patients with relapsed and relapsed/refractory MM. Other MAbs are also showing early promise. More ongoing clinical research is required to identify optimal combination regimens and biomarkers that may help predict response to specific MAb-based combinations. C1 [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lonial, Sagar] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Jakubowiak, Andrzej J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Harousseau, Jean-Luc] Ctr Rene Gauducheau, F-44035 Nantes, France. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu FU Bristol-Myers Squibb FX All authors contributed to the concept and design of the review, the interpretation of the data, and the drafting and critical revision of the manuscript. All authors approved the final manuscript version for publication. The authors would like to thank Stephen Collins, MS, and Ted Everson, PhD, who provided medical writing services, funded by Bristol-Myers Squibb. NR 57 TC 46 Z9 47 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2011 VL 154 IS 6 BP 745 EP 754 DI 10.1111/j.1365-2141.2011.08790.x PG 10 WC Hematology SC Hematology GA 816MG UT WOS:000294604300010 PM 21777223 ER PT J AU Richardson, PG Laubach, J Mitsiades, CS Schlossman, R Hideshima, T Redman, K Chauhan, D Ghobrial, IM Munshi, N Anderson, KC AF Richardson, Paul G. Laubach, Jacob Mitsiades, Constantine S. Schlossman, Robert Hideshima, Teru Redman, Katherine Chauhan, Dharminder Ghobrial, Irene M. Munshi, Nikhil Anderson, Kenneth C. TI Managing multiple myeloma: the emerging role of novel therapies and adapting combination treatment for higher risk settings SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE multiple myeloma; malignancy; therapies ID UNDETERMINED SIGNIFICANCE; THERAPEUTIC APPLICATIONS; MONOCLONAL GAMMOPATHY; LONG-TERM; KAPPA-B; DEXAMETHASONE; LENALIDOMIDE; BORTEZOMIB; SURVIVAL; TRIAL AB Novel therapies have transformed the treatment paradigm for multiple myeloma with significant improvements in survival now seen in both younger and older patients. Nonetheless, the disease is heterogeneous and high-risk patients in particular continue to have poor outcome. Moreover, the disease remains incurable. Efforts to refine risk stratification and disease characteristics continue with the use of cytogenetics, enhanced imaging techniques and other new technologies, such as genomics. The integration of novel therapies into induction therapy, consolidation and maintenance continues to evolve, and the appropriate use of combination strategies including proteasome inhibition and immunomodulatory treatment is emerging as a platform with application across the disease spectrum. Despite these advances, resistance to novel agents occurs and so the identification of new targets and the recognition of clonal heterogeneity are especially important as improvements to current treatment strategies are developed, with the goal of further improving patient outcome. C1 [Richardson, Paul G.; Laubach, Jacob; Mitsiades, Constantine S.; Schlossman, Robert; Hideshima, Teru; Redman, Katherine; Chauhan, Dharminder; Ghobrial, Irene M.; Munshi, Nikhil; Anderson, Kenneth C.] Harvard Univ, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Med Sch Boston, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Harvard Univ, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Med Sch Boston, 44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 41 TC 14 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 2011 VL 154 IS 6 BP 755 EP 762 DI 10.1111/j.1365-2141.2011.08791.x PG 8 WC Hematology SC Hematology GA 816MG UT WOS:000294604300011 PM 21732930 ER PT J AU Kirchhoff, AC Krull, KR Ness, KK Armstrong, GT Park, ER Stovall, M Robison, LL Leisenring, W AF Kirchhoff, Anne C. Krull, Kevin R. Ness, Kirsten K. Armstrong, Gregory T. Park, Elyse R. Stovall, Marilyn Robison, Leslie L. Leisenring, Wendy TI Physical, Mental, and Neurocognitive Status and Employment Outcomes in the Childhood Cancer Survivor Study Cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LONG-TERM SURVIVORS; QUALITY-OF-LIFE; ADULT SURVIVORS; SOCIAL OUTCOMES; UNEMPLOYMENT; LIMITATIONS AB Introduction: We examined the relationship of physical, mental, and neurocognitive function with employment and occupational status in the Childhood Cancer Survivor Study. Methods: We included survivors 25 years or older with available short form-36 (physical and mental health component scores), brief symptom inventory (depression, anxiety, and somatization), and neurocognitive questionnaire (task efficiency, emotional regulation, organization, and memory). We generated relative risks (RR) from generalized linear models for these measures on unemployment (n = 5,386) and occupation (n = 3,763) outcomes adjusted for demographic and cancer-related factors and generated sex-stratified models. Results: Poor physical health was associated with an almost eightfold higher risk of health-related unemployment (P < 0.001) compared to survivors with normal physical health. Male survivors with somatization and memory problems were approximately 50% (P < 0.05 for both) more likely to report this outcome, whereas task efficiency limitations were significant for both sexes (males: RR = 2.43, P < 0.001; females: RR = 2.28, P < 0.001). Employed female survivors with task efficiency, emotional regulation, and memory limitations were 13% to 20% (P < 0.05 for all) less likely to work in professional or managerial occupations than unaffected females. Conclusions: Physical problems may cause much of the health-related unemployment among childhood cancer survivors. Whereas both male and female survivors with neurocognitive deficits-primarily in task efficiencies-are at risk for unemployment, employed female survivors with neurocognitive deficits may face poor occupational outcomes more often than males. Impact: Childhood cancer survivors are at risk for poor employment outcomes. Screening and intervention for physical, mental, and neurocognitive limitations could improve employment outcomes for this population. Cancer Epidemiol Biomarkers Prev; 20(9); 1838-49. (C)2011 AACR. C1 [Kirchhoff, Anne C.] Huntsman Canc Inst, Canc Control & Populat Sci Res Program, Salt Lake City, UT 84112 USA. [Kirchhoff, Anne C.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. [Krull, Kevin R.; Ness, Kirsten K.; Armstrong, Gregory T.; Robison, Leslie L.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. [Park, Elyse R.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Leisenring, Wendy] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Leisenring, Wendy] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. RP Kirchhoff, AC (reprint author), Huntsman Canc Inst, Canc Control & Populat Sci Res Program, 2000 Circle Hope, Salt Lake City, UT 84112 USA. EM Anne.Kirchhoff@hci.utah.edu FU National Cancer Institute [U24 CA55727]; Cancer Center [CA 21765]; American, Syrian, Lebanese Associated Charities (ALSAC) FX The Childhood Cancer Survivor Study is funded by the National Cancer Institute (U24 CA55727, principal investigator (L.L. Robison). Support to St. Jude Children's Research Hospital was also provided by the Cancer Center Support (CORE) grant (CA 21765) and by the American, Syrian, Lebanese Associated Charities (ALSAC). NR 33 TC 25 Z9 25 U1 21 U2 69 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 SEP PY 2011 VL 20 IS 9 BP 1838 EP 1849 DI 10.1158/1055-9965.EPI-11-0239 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 816NN UT WOS:000294609200005 PM 21844244 ER PT J AU Demirtas-Tatlidede, A Freitas, C Pascual-Leone, A Schmahmann, JD AF Demirtas-Tatlidede, Asli Freitas, Catarina Pascual-Leone, Alvaro Schmahmann, Jeremy D. TI Modulatory Effects of Theta Burst Stimulation on Cerebellar Nonsomatic Functions SO CEREBELLUM LA English DT Article DE Transcranial magnetic stimulation (TMS); Theta burst stimulation (TBS); Vermis; Cerebellum; Somatovisceral integration; Nonsomatic modulation ID POSITRON-EMISSION-TOMOGRAPHY; CLASSICALLY-CONDITIONED BRADYCARDIA; TRANSCRANIAL MAGNETIC STIMULATION; COGNITIVE-AFFECTIVE SYNDROME; HUMAN MOTOR CORTEX; HYPOTHALAMO-CEREBELLAR; CARDIOVASCULAR CONTROL; ANGIOTENSIN-II; INTERPOSITUS NUCLEAR; PREFRONTAL CORTEX AB Clinical and functional imaging studies suggest that the cerebellar vermis is involved in the regulation of a range of nonsomatic functions including cardiovascular control, thirst, feeding behavior, and primal emotions. Cerebello-hypothalamic circuits have been postulated to be a potential neuroanatomical substrate underlying this modulation. We tested this putative relationship between the cerebellar vermis and nonsomatic functions by stimulating the cerebellum noninvasively via neuronavigated transcranial magnetic stimulation. In this randomized, counter-balanced, within-subject study, intermittent theta burst stimulation (TBS) was applied on three different days to the vermis and the right and left cerebellar hemispheres of 12 right-handed normal subjects with the aim of modulating activity in the targeted cerebellar structure. TBS-associated changes were investigated via cardiovascular monitoring, a series of emotionally arousing picture stimuli, subjective analog scales for primal emotions, and the Profile of Mood States test. All 36 sessions of cerebellar stimulation were tolerated well without serious adverse events. Cardiovascular monitoring pointed to a mild but significant decrease in heart rate subsequent to vermal stimulation; no changes were detected in systolic or diastolic blood pressure measurements. Subjective ratings detected a significant increase in Thirst and a trend toward increased Appetite following vermal stimulation. These observations are consistent with existing neurophysiological and neuroimaging data indicating a role for the cerebellum in the regulation of visceral responses. In conjunction with the modulatory function of the cerebellum, our results suggest a role for the vermis in somatovisceral integration likely through cerebello-hypothalamic pathways. Further research is warranted to elucidate the potential mechanisms underlying the cerebellar modulation of nonsomatic functions. C1 [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Ataxia Unit, Cognit Behav Neurol Unit, Lab Neuroanat & Cerebellar Neurobiol,Dept Neurol, Boston, MA 02114 USA. [Demirtas-Tatlidede, Asli; Freitas, Catarina; Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat, Behav Neurol Unit, Boston, MA 02215 USA. [Demirtas-Tatlidede, Asli; Freitas, Catarina; Pascual-Leone, Alvaro; Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Ataxia Unit, Cognit Behav Neurol Unit, Lab Neuroanat & Cerebellar Neurobiol,Dept Neurol, CPZS 340,175 Cambridge St, Boston, MA 02114 USA. EM jschmahmann@partners.org FU National Center for Research Resources [RR025758]; National Institutes of Health [K 24 RR018875]; Foundation for Science and Technology, Portugal [SFRH/BPD/44126/2008]; Birmingham Foundation; MINDlink Foundation; Executive Committee on Research of the Massachusetts General Hospital FX We gratefully acknowledge the contributions of Shirley Fecteau, Ph.D., Elke Praeg, Ph.D., and Lindsay Oberman, Ph.D., as well as the outstanding nursing staff at the Harvard-Thorndike Clinical Research Center. Work on this study was supported in part by Grant Number UL1 RR025758-Harvard Clinical and Translational Science Center, from the National Center for Research Resources and National Institutes of Health grant K 24 RR018875 to APL. CF was supported by the Foundation for Science and Technology, Portugal (SFRH/BPD/44126/2008). JDS was supported by the Birmingham Foundation, the MINDlink Foundation, and the Executive Committee on Research of the Massachusetts General Hospital. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 120 TC 11 Z9 11 U1 4 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1473-4222 J9 CEREBELLUM JI Cerebellum PD SEP PY 2011 VL 10 IS 3 SI SI BP 495 EP 503 DI 10.1007/s12311-010-0230-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 818WS UT WOS:000294787200016 PM 21132574 ER PT J AU Abu Dayyeh, BK Lautz, D Thompson, CC AF Abu Dayyeh, Barham K. Lautz, David Thompson, Christopher C. TI Gastrojejunal Stoma Diameter Predicts Weight Regain After Roux-en-Y Gastric Bypass Reply SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter C1 [Abu Dayyeh, Barham K.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Abu Dayyeh, Barham K.; Thompson, Christopher C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lautz, David] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Thompson, Christopher C.] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Abu Dayyeh, BK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 3 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD SEP PY 2011 VL 9 IS 9 BP 805 EP 805 DI 10.1016/j.cgh.2011.06.015 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 817MT UT WOS:000294678400026 ER PT J AU Kotton, CN AF Kotton, Camille Nelson TI Vaccinations in Kidney Transplant Patients: Searching for Optimal Protection SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID INFLUENZA VACCINATION; PANDEMIC H1N1; RECIPIENTS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 11 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2011 VL 6 IS 9 BP 2099 EP 2101 DI 10.2215/CJN.07330711 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 817EN UT WOS:000294654200001 PM 21852666 ER PT J AU Demirjian, S Chertow, GM Zhang, JH O'Connor, TZ Vitale, J Paganini, EP Palevsky, PM AF Demirjian, Sevag Chertow, Glenn M. Zhang, Jane Hongyuan O'Connor, Theresa Z. Vitale, Joseph Paganini, Emil P. Palevsky, Paul M. CA VA NIH Acute Renal Failure Trial N TI Model to Predict Mortality in Critically Ill Adults with Acute Kidney Injury SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; INTENSIVE-CARE-UNIT; REPLACEMENT THERAPY; TRIAL NETWORK; CLASSIFICATION-SYSTEM; ACUTE PHYSIOLOGY; RISK-ADJUSTMENT; SCORING SYSTEMS; SEVERITY; SUPPORT AB Background and objectives Acute kidney injury (AKI) requiring dialysis is associated with high mortality. Most prognostic tools used to describe case complexity and to project patient outcome lack predictive accuracy when applied in patients with AKI. In this study, we developed an AKI-specific predictive model for 60-day mortality and compared the model to the performance of two generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation II [APACHE II]) scores, and a disease specific (Cleveland Clinic [CCF]) score. Design, setting, participants, & measurements Data from 1122 subjects enrolled in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study; a multicenter randomized trial of intensive versus less intensive renal support in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 VA- and university-affiliated centers. Results The 60-day mortality was 53%. Twenty-one independent predictors of 60-day mortality were identified. The logistic regression model exhibited good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of 0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and CCF, when applied to our cohort, showed relatively poor discrimination, reflected by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and 0.65 (0.62 to 0.69), respectively. Conclusions Our new risk model outperformed existing generic and disease-specific scoring systems in predicting 60-day mortality in critically ill patients with AKI. The current model requires external validation before it can be applied to other patient populations. Clin J Am Soc Nephrol 6: 2114-2120, 2011. doi:10.2215/CJN.02900311 C1 [Demirjian, Sevag; Paganini, Emil P.] Cleveland Clin, Dept Hypertens & Nephrol, Cleveland, OH 44195 USA. [Chertow, Glenn M.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA. [Zhang, Jane Hongyuan; O'Connor, Theresa Z.; Vitale, Joseph] VA Connecticut Healthcare Syst, Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Demirjian, S (reprint author), Cleveland Clin, Dept Hypertens & Nephrol, 9500 Euclid Ave,Q7, Cleveland, OH 44195 USA. EM demirjs@ccf.org NR 24 TC 28 Z9 31 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2011 VL 6 IS 9 BP 2114 EP 2120 DI 10.2215/CJN.02900311 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 817EN UT WOS:000294654200005 PM 21896828 ER PT J AU Davison, BA Cotter, G Sun, HR Chen, L Teerlink, JR Metra, M Felker, GM Voors, AA Ponikowski, P Filippatos, G Greenberg, B Teichman, SL Unemori, E Koch, GG AF Davison, Beth A. Cotter, Gad Sun, Hengrui Chen, Li Teerlink, John R. Metra, Marco Felker, G. Michael Voors, Adriaan A. Ponikowski, Piotr Filippatos, Gerasimos Greenberg, Barry Teichman, Sam L. Unemori, Elaine Koch, Gary G. TI Permutation criteria to evaluate multiple clinical endpoints in a proof-of-concept study: lessons from Pre-RELAX-AHF SO CLINICAL RESEARCH IN CARDIOLOGY LA English DT Article DE Heart failure; Statistics; Clinical trials; Phase II ID ACUTE HEART-FAILURE; TRIALS; ROLOFYLLINE; ANTAGONIST; THERAPIES; DESIGN AB Clinically relevant endpoints cannot be routinely targeted with reasonable power in a small study. Hence, proof-of-concept studies are often powered to a primary surrogate endpoint. However, in acute heart failure (AHF) effects on surrogates have not translated into clinical benefit in confirmatory studies. Although observing an effect on one of many endpoints due to chance is likely, observing concurrent positive trends across several outcomes by chance is usually unlikely. Pre-RELAX-AHF, which compared 4 relaxin doses with placebo in AHF, has shown favourable trends versus placebo (one-sided P < 0.10) on six of nine clinical endpoints in the 30 mu g/kg/day group. To illustrate evaluation of multiple, correlated clinical endpoints for evidence of efficacy and for dose selection, a permutation method was applied retrospectively. By randomly re-assigning the treatment group to the actual data for each of the 229 subjects, 20,000 permutation samples were constructed. The permutation P value for at least six favourable trends among nine endpoints in any dose groups was 0.0073 (99.9% CI 0.0053-0.0093). This is higher than would be expected if the endpoints were uncorrelated (0.00026), but much lower than the probability of observing one of nine comparisons significant at the traditional two-sided P < 0.05 (0.74). Thus, the result was unlikely due to correlated endpoints or to chance. Examining consistency of effect across multiple clinical endpoints in a proof-of-concept study may identify efficacious therapies and enable dose selection for confirmatory trials. The merit of the approach described requires confirmation through prospective application in designing future studies. C1 [Davison, Beth A.; Cotter, Gad; Sun, Hengrui] Momentum Res Inc, Durham, NC USA. [Chen, Li; Koch, Gary G.] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. [Teerlink, John R.] Univ Calif San Francisco, Cardiol Sect, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Metra, Marco] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy. [Felker, G. Michael] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands. [Ponikowski, Piotr] Med Univ, Mil Hosp, Dept Cardiol, Dept Hlth Sci, Wroclaw, Poland. [Filippatos, Gerasimos] Univ Athens, Hosp Attikon, Athens, Greece. [Greenberg, Barry] Univ Calif San Diego, Adv Heart Failure Program, San Diego, CA 92103 USA. [Teichman, Sam L.; Unemori, Elaine] Corthera Inc, San Mateo, CA USA. RP Davison, BA (reprint author), Momentum Res Inc, Durham, NC USA. EM bethdavison@momentum-research.com RI Teerlink, John/D-2986-2012; Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Davison, Beth/0000-0003-2374-6449; Metra, Marco/0000-0001-6691-8568 FU Corthera, Inc. FX The authors thank Jill El-Khorazaty, Michael Hussey, and Daniela Sotres for their review and helpful comments. Pre-RELAX-AHF was sponsored by Corthera, Inc., a subsidiary of Novartis Pharmaceuticals Corp. (San Mateo, California). NR 18 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-0684 J9 CLIN RES CARDIOL JI Clin. Res. Cardiol. PD SEP PY 2011 VL 100 IS 9 BP 745 EP 753 DI 10.1007/s00392-011-0304-5 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 817RE UT WOS:000294690900004 PM 21416190 ER PT J AU Kanoni, S Nettleton, JA Hivert, MF Ye, Z van Rooij, FJA Shungin, D Sonestedt, E Ngwa, JS Wojczynski, MK Lemaitre, RN Gustafsson, S Anderson, JS Tanaka, T Hindy, G Saylor, G Renstrom, F Bennett, AJ van Duijn, CM Florez, JC Fox, CS Hofman, A Hoogeveen, RC Houston, DK Hu, FB Jacques, PF Johansson, I Lind, L Liu, YM McKeown, N Ordovas, J Pankow, JS Sijbrands, EJG Syvanen, AC Uitterlinden, AG Yannakoulia, M Zillikens, MC Wareham, NJ Prokopenko, I Bandinelli, S Forouhi, NG Cupples, LA Loos, RJ Hallmans, G Dupuis, J Langenberg, C Ferrucci, L Kritchevsky, SB McCarthy, MI Ingelsson, E Borecki, IB Witteman, JCM Orho-Melander, M Siscovick, DS Meigs, JB Franks, PW Dedoussis, GV AF Kanoni, Stavroula Nettleton, Jennifer A. Hivert, Marie-France Ye, Zheng van Rooij, Frank J. A. Shungin, Dmitry Sonestedt, Emily Ngwa, Julius S. Wojczynski, Mary K. Lemaitre, Rozenn N. Gustafsson, Stefan Anderson, Jennifer S. Tanaka, Toshiko Hindy, George Saylor, Georgia Renstrom, Frida Bennett, Amanda J. van Duijn, Cornelia M. Florez, Jose C. Fox, Caroline S. Hofman, Albert Hoogeveen, Ron C. Houston, Denise K. Hu, Frank B. Jacques, Paul F. Johansson, Ingegerd Lind, Lars Liu, Yongmei McKeown, Nicola Ordovas, Jose Pankow, James S. Sijbrands, Eric J. G. Syvanen, Ann-Christine Uitterlinden, Andre G. Yannakoulia, Mary Zillikens, M. Carola Wareham, Nick J. Prokopenko, Inga Bandinelli, Stefania Forouhi, Nita G. Cupples, L. Adrienne Loos, Ruth J. Hallmans, Goran Dupuis, Josee Langenberg, Claudia Ferrucci, Luigi Kritchevsky, Stephen B. McCarthy, Mark I. Ingelsson, Erik Borecki, Ingrid B. Witteman, Jacqueline C. M. Orho-Melander, Marju Siscovick, David S. Meigs, James B. Franks, Paul W. Dedoussis, George V. CA MAGIC Investigators TI Total Zinc Intake May Modify the Glucose-Raising Effect of a Zinc Transporter (SLC30A8) Variant A 14-Cohort Meta-analysis SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; GENE-ENVIRONMENT INTERACTIONS; RISK LOCI; INSULIN-RESISTANCE; CELL-FUNCTION; HOMEOSTASIS; SUPPLEMENTATION; ZNT8; POLYMORPHISMS; EXPRESSION AB OBJECTIVE-Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for beta-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants. RESEARCH DESIGN AND METHODS-We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes. RESULTS-We observed a significant association of total zinc intake with lower fasting glucose levels (beta-coefficient +/- SE per 1 mg/day of zinc intake: -0.0012 +/- 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (beta-coefficient +/- SE per A allele for 1 mg/day of greater total zinc intake: -0.0017 +/- 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant. CONCLUSIONS Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels. Diabetes 60:2407-2416, 2011 C1 [Kanoni, Stavroula; Yannakoulia, Mary; Dedoussis, George V.] Harokopio Univ, Dept Nutr Dietet, Athens, Greece. [Kanoni, Stavroula] Wellcome Trust Sanger Inst, Hinxton, England. [Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr, Div Epidemiol Htunan Genet & Environm Sci, Houston, TX USA. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada. [Ye, Zheng; Wareham, Nick J.; Forouhi, Nita G.; Loos, Ruth J.; Langenberg, Claudia] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England. [van Rooij, Frank J. A.; van Duijn, Cornelia M.; Hofman, Albert; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [van Rooij, Frank J. A.; van Duijn, Cornelia M.; Hofman, Albert; Sijbrands, Eric J. G.; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.] NGI NCHA, Leiden, Netherlands. [Shungin, Dmitry; Renstrom, Frida; Hallmans, Goran; Franks, Paul W.] Umea Univ Hosp, Dept Publ Hlth & Clin Med, Med Sect, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. [Shungin, Dmitry; Sonestedt, Emily; Hindy, George; Renstrom, Frida; Orho-Melander, Marju; Franks, Paul W.] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Shungin, Dmitry; Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden. [Ngwa, Julius S.; Cupples, L. Adrienne; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Wojczynski, Mary K.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [Lemaitre, Rozenn N.; Siscovick, David S.] Univ Washington, Dept Med & Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Gustafsson, Stefan; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Anderson, Jennifer S.; Saylor, Georgia] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Renstrom, Frida; Hu, Frank B.; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Bennett, Amanda J.; Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Fox, Caroline S.; Cupples, L. Adrienne; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Hoogeveen, Ron C.] Baylor Coll Med, Dept Med, Sect Atherosclerosis & Vasc Med, Houston, TX 77030 USA. [Hoogeveen, Ron C.] Methodist DeBakey Heart Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. [Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med,Sticht Ctr Aging, Winston Salem, NC 27103 USA. [Jacques, Paul F.; McKeown, Nicola] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA. [Lind, Lars; Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Liu, Yongmei] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [McKeown, Nicola] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Ordovas, Jose] Tufts Univ, Jean Mayer USDA HNRCA, Nutr & Genom Lab, Boston, MA 02111 USA. [Pankow, James S.] Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA. [Sijbrands, Eric J. G.; Uitterlinden, Andre G.; Zillikens, M. Carola] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Prokopenko, Inga; McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy. [McCarthy, Mark I.] Churchill Hosp, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 7LJ, England. [Meigs, James B.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Diabet Res Unit, Boston, MA 02114 USA. RP Kanoni, S (reprint author), Harokopio Univ, Dept Nutr Dietet, Athens, Greece. EM stavroula.kanoni@sanger.ac.uk; paul.franks@med.lu.se; dedousi@hua.gr RI Prokopenko, Inga/H-3241-2014; Sonestedt, Emily/I-3814-2016; Hindy, George/H-1864-2016; OI Prokopenko, Inga/0000-0003-1624-7457; Sonestedt, Emily/0000-0002-0747-4562; Ordovas, Jose/0000-0002-7581-5680; Cupples, L. Adrienne/0000-0003-0273-7965; Shungin, Dmitry/0000-0001-7900-5856; Hindy, George/0000-0002-7257-9299; Sijbrands, Eric/0000-0001-8857-7389; Dupuis, Josee/0000-0003-2871-3603; Kritchevsky, Stephen/0000-0003-3336-6781; Forouhi, Nita/0000-0002-5041-248X FU Medical Research Council [G0701863, MC_U106179471, MC_U106188470, MC_UP_A100_1003]; NHLBI NIH HHS [R01 HL087700]; Wellcome Trust [090532] NR 48 TC 39 Z9 41 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2011 VL 60 IS 9 BP 2407 EP 2416 DI 10.2337/db11-0176 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 817TN UT WOS:000294699600024 PM 21810599 ER PT J AU Lyssenko, V Eliasson, L Kotova, O Pilgaard, K Wierup, N Salehi, A Wendt, A Jonsson, A De Marinis, YZ Berglund, LM Taneera, J Balhuizen, A Hansson, O Osmark, P Duner, P Brons, C Stancakova, A Kuusisto, J Bugliani, M Saxena, R Ahlqvist, E Kieffer, TJ Tuomi, T Isomaa, B Melander, O Sonestedt, E Orho-Melander, M Nilsson, P Bonetti, S Bonadonna, R Miccoli, R DelPrato, S Marchetti, P Madsbad, S Poulsen, P Vaag, A Laakso, M Gomez, MF Groop, L AF Lyssenko, Valeriya Eliasson, Lena Kotova, Olga Pilgaard, Kasper Wierup, Nils Salehi, Albert Wendt, Anna Jonsson, Anna De Marinis, Yang Z. Berglund, Lisa M. Taneera, Jalal Balhuizen, Alexander Hansson, Ola Osmark, Peter Duner, Pontus Brons, Charlotte Stancakova, Alena Kuusisto, Johanna Bugliani, Marco Saxena, Richa Ahlqvist, Emma Kieffer, Timothy J. Tuomi, Tiinamaija Isomaa, Bo Melander, Olle Sonestedt, Emily Orho-Melander, Marju Nilsson, Peter Bonetti, Sara Bonadonna, Riccardo Miccoli, Roberto DelPrato, Stefano Marchetti, Piero Madsbad, Sten Poulsen, Pernille Vaag, Allan Laakso, Markku Gomez, Maria F. Groop, Leif TI Pleiotropic Effects of GIP on Islet Function Involve Osteopontin SO DIABETES LA English DT Article ID DEPENDENT INSULINOTROPIC POLYPEPTIDE; GASTRIC-INHIBITORY POLYPEPTIDE; LOW-BIRTH-WEIGHT; GLUCAGON-LIKE PEPTIDE-1; PANCREATIC BETA-CELLS; YOUNG MEN BORN; GLUCOSE-TOLERANCE; ORAL GLUCOSE; ASSOCIATION ANALYSIS; SUSCEPTIBILITY LOCI AB OBJECTIVE-The incretin hormone GIP (glucose-dependent insulinotropic polypeptide) promotes pancreatic beta-cell function by potentiating insulin secretion and beta-cell proliferation. Recently, a combined analysis of several genome-wide association studies (Meta-analysis of Glucose and Insulin-Related Traits Consortium [MAGIC]) showed association to postprandial insulin at the GIP receptor (GIPR) locus. Here we explored mechanisms that could explain the protective effects of GIP on islet function. RESEARCH DESIGN AND METHODS-Associations of GIPR rs10423928 with metabolic and anthropometric phenotypes in both nondiabetic (N = 53,730) and type 2 diabetic individuals (N = 2,731) were explored by combining data from 11 studies.Insulin secretion was measured both in vivo in nondiabetic subjects and in vitro in islets from cadaver donors. Insulin secretion was also measured in response to exogenous GIP. The in vitro measurements included protein and gene expression as well as measurements of beta-cell viability and proliferation. RESULTS-The A allele of GIPR rs10423928 was associated with impaired glucose- and GIP-stimulated insulin secretion and a decrease in BMI, lean body mass, and waist circumference. The decrease in BMI almost completely neutralized the effect of impaired insulin secretion on risk of type 2 diabetes. Expression of GIPR mRNA was decreased in human islets from carriers of the A allele or patients with type 2 diabetes. GIP stimulated osteopontin (OPN) mRNA and protein expression. OPN expression was lower in carriers of the A allele. Both GIP and OPN prevented cytokine-induced reduction in cell viability (apoptosis). In addition, OPN stimulated cell proliferation in insulin-secreting cells. CONCLUSIONS-These findings support beta-cell proliferative and antiapoptotic roles for GIP in addition to its action as an incretin hormone. Identification of a link between GIP and OPN may shed new light on the role of GIP in preservation of functional beta-cell mass in humans. Diabetes 60:2424-2433, 2011 C1 [Lyssenko, Valeriya; Kotova, Olga; Berglund, Lisa M.] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Vasc ET Coupling, Malmo, Sweden. [Pilgaard, Kasper; Brons, Charlotte; Poulsen, Pernille; Vaag, Allan] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Wierup, Nils] Lund Univ, Dept Expt Med Sci, Malmo, Sweden. [Salehi, Albert; Balhuizen, Alexander] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Div Endocrine Pharmacol, Malmo, Sweden. [Duner, Pontus; Gomez, Maria F.] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Expt Cardiovasc Res Unit, Malmo, Sweden. [Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Bugliani, Marco; Miccoli, Roberto; DelPrato, Stefano; Marchetti, Piero] Univ Pisa, Dept Endocrinol & Metab, Pisa, Italy. [Bugliani, Marco; Marchetti, Piero] AOUP Pisa, Pisa, Italy. [Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kieffer, Timothy J.] Univ British Columbia, Dept Surg, Lab Mol & Cellular Med, Inst Life Sci, Vancouver, BC V6T 1W5, Canada. [Kieffer, Timothy J.] Univ British Columbia, Dept Cellular & Physiol Sci, Lab Mol & Cellular Med, Inst Life Sci, Vancouver, BC V5Z 1M9, Canada. [Tuomi, Tiinamaija; Isomaa, Bo] Folkhalsan Res Ctr, Helsinki, Finland. [Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. [Tuomi, Tiinamaija] Univ Helsinki, Res Program Mol Med, Helsinki, Finland. [Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland. [Melander, Olle] Malmo Univ Hosp, Ctr Emergency Med, Malmo, Sweden. [Melander, Olle] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Clin Res Ctr, Malmo, Sweden. [Sonestedt, Emily; Orho-Melander, Marju] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Bonetti, Sara; Bonadonna, Riccardo] Univ Verona, Dept Med, Sect Endocrinol & Metab Dis, I-37100 Verona, Italy. [Madsbad, Sten] Univ Copenhagen, Hvidovre Hosp, Dept Endocrinol, Copenhagen, Denmark. RP Lyssenko, V (reprint author), Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Vasc ET Coupling, Malmo, Sweden. EM valeriya.lyssenko@med.lu.se RI Hansson, Ola/F-1793-2011; Marchetti, Piero/J-7439-2013; Gomez, Maria/D-3696-2014; Sonestedt, Emily/I-3814-2016; OI Wendt, Anna/0000-0001-8807-5979; Bonadonna, Riccardo/0000-0002-9809-1005; Hansson, Ola/0000-0002-7394-7639; Marchetti, Piero/0000-0003-4907-0635; Gomez, Maria/0000-0001-6210-3142; Sonestedt, Emily/0000-0002-0747-4562; Taneera, Jalal/0000-0002-3341-1063; Eliasson, Lena/0000-0002-6467-5029; Tuomi, Tiinamaija/0000-0002-8306-6202 FU Linnaeus grant [349-2008-2974]; Swedish Research Council [521-2007-4037]; Knut & Alice Wallenberg Foundation [KAW 2009-0243]; Novo Nordisk; Swedish Diabetes Foundation [2009-060]; Ahlen; Ake Wiberg; Magnus Bergwall; Tore Nilsson; Fredrik and Ingrid Thuring; Crafoord; Albert Pahlsson; Lars Hierta Memorial; Royal Physiographic Society; Foundation of the National Board of Health and Welfare; Malmo University Hospital; European Foundation for the Study of Diabetes (EFSD); EU [2007-201413]; CEED3 [2008-223211]; IngaBritt och Arne Lundberg's Research Foundation [359]; Torsten och Ragnar Soderbergs Stiftelser [MT33/09]; Academy of Finland; Finnish Diabetes Research Foundation; EC [LSHM-CT-2006-518153]; University of Verona; EFSD/Novartis; ForiSID-Eli Lilly Italy FX The studies at Lund University were supported by a Linnaeus grant (349-2008-2974) as well as several other grants from the Swedish Research Council (Grant 521-2007-4037; Exodiab 2009-1039 and 2009-4120) and an equipment grant from the Knut & Alice Wallenberg Foundation (KAW 2009-0243), as well as by grants from the following foundations: Novo Nordisk, the Swedish Diabetes Foundation (2009-060), Ahlen, Ake Wiberg, Magnus Bergwall, Tore Nilsson, Fredrik and Ingrid Thuring, Crafoord, Albert Pahlsson, Lars Hierta Memorial, Royal Physiographic Society, the Foundation of the National Board of Health and Welfare, Malmo University Hospital, the European Foundation for the Study of Diabetes (EFSD) and the EU-7th Framework Programme projects ENGAGE (2007-201413) and CEED3 (2008-223211), IngaBritt och Arne Lundberg's Research Foundation (Grant 359), and Torsten och Ragnar Soderbergs Stiftelser (MT33/09). M.F.G. and L.E. are senior scientists at the Swedish Heart and Lung Foundations and Swedish Research Council, respectively. Work in Kuopio, Finland, was supported by grants from the Academy of Finland and Finnish Diabetes Research Foundation. Work in Italy was supported by grants from the EC Eurodia project, the 6th Framework Programme (LSHM-CT-2006-518153) to M.B. and P.M., University of Verona to R.B., E.B., and M.M. of the Verona Newly Diagnosed Type 2 Diabetes Study, and from the EFSD/Novartis Programme to R.B. The GENFIEV study was supported by ForiSID-Eli Lilly Italy and from the EFSD/Novartis Programme (R.M. and S.D.P.). No other potential conflicts of interest relevant to this article were reported. NR 52 TC 32 Z9 32 U1 0 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2011 VL 60 IS 9 BP 2424 EP 2433 DI 10.2337/db10-1532 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 817TN UT WOS:000294699600026 PM 21810601 ER PT J AU Kardos, M Lundquist, A Misialek, M Friedman, LS AF Kardos, Marisa Lundquist, Andrew Misialek, Michael Friedman, Lawrence S. TI A Rare Presentation of an Uncommon Malignancy: Thromboembolism in a Patient with a Gastrointestinal Stromal Tumor SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE GIST; Gastrointestinal stromal tumor; Thromboembolism; Deep vein thrombosis; Pulmonary embolism; Malignancy ID VENOUS THROMBOEMBOLISM; RISK-FACTORS; CANCER C1 [Kardos, Marisa; Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. [Kardos, Marisa; Friedman, Lawrence S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Lundquist, Andrew; Friedman, Lawrence S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Misialek, Michael] Newton Wellesley Hosp, Dept Pathol, Newton, MA 02462 USA. [Friedman, Lawrence S.] Harvard Univ, Sch Med, Boston, MA USA. RP Kardos, M (reprint author), 2014 Washington St, Newton, MA 02462 USA. EM marisa.kardos@tufts.edu; alundquist@partners.org; mmisialek@partners.org; lfriedman@partners.org NR 9 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 2011 VL 56 IS 9 BP 2711 EP 2714 DI 10.1007/s10620-011-1811-y PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 819BJ UT WOS:000294800100027 PM 21732216 ER PT J AU Tharp, AT Vasterling, JJ Sullivan, G Han, XT Davis, T Deitch, EA Constans, J AF Tharp, Andra Teten Vasterling, Jennifer J. Sullivan, Greer Han, Xiaotong Davis, Teri Deitch, Elizabeth A. Constans, Joseph TI Effects of Pre- and Post-Katrina Nonviolent and Violent Experiences on Male Veterans' Psychological Functioning SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Article DE disaster; violence; veterans; posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; HURRICANE KATRINA; HEALTH; VICTIMIZATION; METAANALYSIS; POPULATION; DEPRESSION; OUTCOMES; ALCOHOL; TSUNAMI AB Background: Identifying individuals at risk for mental health problems after a disaster often involves assessing potentially traumatic exposures inherent to the disaster. Survivors of disasters also may have been exposed, both before and during the event, to trauma not directly related to the disaster. A substantial literature suggests exposure to interpersonal violence may have more severe negative outcomes than exposure to nonviolent events; however, it is unclear whether violent vs nonviolent exposures before and during a disaster have differential effects on postdisaster psychological functioning. Methods: We examined the associations of violent and nonviolent exposures before and during Hurricane Katrina with postdisaster psychological functioning in a sample of male military veterans. Results: Violent and nonviolent exposures post-Hurricane Katrina as well as pre-Katrina violent exposures were significantly associated with symptoms of posttraumatic stress disorder, panic, and generalized anxiety disorder more than 2 years after the storm. Moreover, veterans who reported violent exposures pre-Katrina were more than 4 times more likely to have reexperienced interpersonal violence during Katrina than those who did not report such exposures. Conclusions: Results suggest assessing disaster-specific experiences in addition to predisaster interpersonal violence may be important for identifying and triaging individuals at risk for postdisaster mental health problems. (Disaster Med Public Health Preparedness. 2011;5:S227-S234) C1 [Tharp, Andra Teten] Baylor Coll Med, Houston, TX 77030 USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Sullivan, Greer; Han, Xiaotong; Davis, Teri] Univ Arkansas Med Sci, S Cent VA Mental Illness Res Educ & Clin Ctr, Little Rock, AR 72205 USA. [Deitch, Elizabeth A.] Univ New Orleans, New Orleans, LA 70148 USA. [Constans, Joseph] Tulane Univ, S Cent VA Mental Illness Res Educ & Clin Ctr, SE Louisiana Vet Healthcare Syst, New Orleans, LA 70118 USA. RP Tharp, AT (reprint author), Ctr Dis Control & Prevent, Natl Ctr Injury Prevent & Control, 4770 Buford Hwy,MS F-64, Atlanta, GA 30341 USA. EM atharpn@cdc.gov RI Schueter, nicos/A-3625-2014 FU Department of Veterans Affairs' South Central Mental Illness Research, Education, and Clinical Center FX This work was supported by the Department of Veterans Affairs' South Central Mental Illness Research, Education, and Clinical Center. The work does not represent the views of the Department of Veterans Affairs or the US government. Data were collected before Andra Teten Tharp joined the Centers for Disease Control and Prevention. NR 30 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD SEP PY 2011 VL 5 SU 2 BP S227 EP S234 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 817ZH UT WOS:000294716700012 PM 21908700 ER PT J AU Baddley, JW Winthrop, KL Patkar, NM Delzell, E Beukelman, T Xie, FL Chen, L Curtis, JR AF Baddley, John W. Winthrop, Kevin L. Patkar, Nivedita M. Delzell, Elizabeth Beukelman, Timothy Xie, Fenglong Chen, Lang Curtis, Jeffrey R. TI Geographic Distribution of Endemic Fungal Infections among Older Persons, United States SO EMERGING INFECTIOUS DISEASES LA English DT Article ID OPPORTUNISTIC INFECTIONS; ELDERLY PERSONS; COCCIDIOIDOMYCOSIS; BLASTOMYCOSIS; HOSPITALIZATIONS; HISTOPLASMOSIS; SURVEILLANCE; SENSITIVITY; ARIZONA; USA AB To investigate the epidemiology and geographic distribution of histoplasmosis, coccidioidomycosis, and blastomycosis in older persons in the United States, we evaluated a random 5% sample of national Medicare data from 1999 through 2008. We calculated national, regional, and state-based incidence rates and determined 90-day postdiagnosis mortality rates. We identified 776 cases (357 histoplasmosis, 345 coccidioidomycosis, 74 blastomycosis). Patient mean age was 75.7 years; 55% were male. Histoplasmosis and blastomycosis incidence was highest in the Midwest (6.1 and 1.0 cases/100,000 person-years, respectively); coccidioidomycosis incidence rate was highest in the West (15.2). On the basis of available data, for 86 (11.1%) cases, there was no patient exposure to a traditional disease-endemic area. Knowledge of areas where endemic mycosis incidence is increased may affect diagnostic or prevention measures for older adults at risk. C1 [Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham VA Med Ctr, Birmingham, AL USA. [Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, 229 Tinsley Harrison Tower,1900 Univ Blvd, Birmingham, AL 35294 USA. EM jbaddley@uab.edu FU Agency for Healthcare Research and Quality [R01HS018517]; Amgen FX This study was supported by the Agency for Healthcare Research and Quality (R01HS018517). E.D. received research support from Amgen. NR 18 TC 43 Z9 45 U1 0 U2 3 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD SEP PY 2011 VL 17 IS 9 BP 1664 EP 1669 DI 10.3201/eid1709.101987 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 817FG UT WOS:000294656100012 PM 21888792 ER PT J AU Chen, YI Famous, K Xu, H Choi, JK Mandeville, JB Schmidt, HD Pierce, RC Jenkins, BG AF Chen, Y. Iris Famous, K. Xu, H. Choi, J. -K. Mandeville, Joseph B. Schmidt, H. D. Pierce, R. Christopher Jenkins, Bruce G. TI Cocaine self-administration leads to alterations in temporal responses to cocaine challenge in limbic and motor circuitry SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE addiction; cerebral blood volume; dopamine neurons; MRI; receptors ID STATE FUNCTIONAL CONNECTIVITY; DOPAMINE D2 RECEPTORS; CEREBRAL-BLOOD-FLOW; HUMAN BRAIN; RAT-BRAIN; PREFRONTAL CORTEX; PHARMACOLOGICAL MRI; SEEKING BEHAVIOR; DRUG-ABUSE; ADDICTION AB Chronic use of cocaine is associated with lasting alterations in brain metabolism, circuitry, and receptor properties. We used neuroimaging with pharmacological magnetic resonance imaging to assess alterations in response to cocaine (0.5 mg/kg) in animals trained to self-administer cocaine on a fixed-ratio 5 schedule of reinforcement, as well as saline-yoked controls, after 28 days of cocaine abstinence. We fitted the cerebral blood volume (CBV) curves for full-width half-maximum (FWHM) as well as peak CBV response. There were significant increases in the FWHM of the response curves in the cocaine self-administering (SA) animals as compared with saline-yoked controls in the medial prefrontal cortex (mPFC) and the caudate/putamen (CPu), and increases in peak CBV in the M1 motor cortex, CPu, and pedunculopontine tegmental nucleus. Functional connectivity analysis showed increased correlations in the cocaine SA rats upon acute cocaine challenge, especially in the S1, mPFC, and thalamus. As D3 receptor expression is postulated to increase following chronic cocaine administration, we also examined the response to 0.2 mg/kg of the D3-preferring agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT). Cocaine SA animals showed a decreased overall CBV response to this drug, except in the globus pallidus. The hypothalamus showed a negative CBV change in response to cocaine challenge, similar to that noted with the D3 agonist, and showed a smaller response in the cocaine SA animals than in the controls. Given the good coupling of cerebral hemodynamics with dopamine dynamics previously observed with pharmacological magnetic resonance imaging, these data suggest that increased persistence of dopamine in the prefrontal cortex may be responsible for some of the behavioral alterations observed subsequent to chronic cocaine use. C1 [Chen, Y. Iris; Choi, J. -K.; Mandeville, Joseph B.; Jenkins, Bruce G.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Chen, Y. Iris; Choi, J. -K.; Mandeville, Joseph B.; Jenkins, Bruce G.] Harvard Univ, Sch Med, Boston, MA USA. [Famous, K.] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA. [Xu, H.] Union Hosp, Dept Radiol, Wuhan, Peoples R China. [Schmidt, H. D.; Pierce, R. Christopher] Univ Penn, Sch Med, Dept Psychiat, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. RP Chen, YI (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. EM iris@nmr.mgh.harvard.edu FU NIH [5R01DA016187] FX This work is partially supported by NIH 5R01DA016187. NR 68 TC 16 Z9 16 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP PY 2011 VL 34 IS 5 BP 800 EP 815 DI 10.1111/j.1460-9568.2011.07806.x PG 16 WC Neurosciences SC Neurosciences & Neurology GA 819DL UT WOS:000294805500013 PM 21896062 ER PT J AU Sharma, P Meining, AR Coron, E Lightdale, CJ Wolfsen, HC Bansal, A Bajbouj, M Galiniche, JP Abrams, JA Rastogi, A Gupta, N Michalek, JE Lauwers, GY Wallace, MB AF Sharma, Prateek Meining, Alexander R. Coron, Emmanuel Lightdale, Charles J. Wolfsen, Herbert C. Bansal, Ajay Bajbouj, Monther Galiniche, Jean-Paul Abrams, Julian A. Rastogi, Amit Gupta, Neil Michalek, Joel E. Lauwers, Gregory Y. Wallace, Michael B. TI Real-time increased detection of neoplastic tissue in Barrett's esophagus with probe-based confocal laser endomicroscopy: final results of an international multicenter, prospective, randomized, controlled trial SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID INTESTINAL METAPLASIA; 4-QUADRANT BIOPSY; METHYLENE-BLUE; DYSPLASIA; ENDOSCOPY; CHROMOENDOSCOPY; ADENOCARCINOMA; DIAGNOSIS; CROSSOVER; MINIPROBE AB Background: Probe-based confocal laser endomicroscopy (pCLE) allows real-time detection of neoplastic Barrett's esophagus (BE) tissue. However, the accuracy of pCLE in real time has not yet been extensively evaluated. Objective: To compare the sensitivity and specificity of pCLE in addition to high-definition white-light endoscopy (HD-WLE) with HD-WLE alone for the detection of high-grade dysplasia (HGD) and early carcinoma (EC) in BE. Design: International, prospective, multicenter, randomized, controlled trial. Setting: Five tertiary referral centers. Patients: A total of 101 consecutive BE patients presenting for surveillance or endoscopic treatment of HGD/EC. Interventions: All patients were examined by HD-WLE, narrow-band imaging (NBI), and pCLE, and the findings were recorded before biopsy samples were obtained. The order of HD-WLE and NBI was randomized and performed by 2 independent, blinded encloscopists. All suspicious lesions on HD-WLE or NBI and 4-quadrant random locations were documented. These locations were examined by pCLE, and a presumptive diagnosis of benign or neoplastic (HGD/EC) tissue was made in real time. Finally, biopsies were taken from all locations and were reviewed by a central pathologist, blinded to endoscopic and pCLE data. Main Outcome Measurements: Diagnostic characteristics of pCLE. Results: The sensitivity and specificity for HD-WLE were 34.2% and 92.7%, respectively, compared with 68.3% and 87.8%, respectively, for HD-WLE or pCLE (P = .002 and P < .001, respectively). The sensitivity and specificity for HD-WLE or NB! were 45.0% and 88.2%, respectively, compared with 75.8% and 84.2%, respectively, for HD-WLE, NBI, or pCLE (P = .01 and P = .02, respectively). Use of pCLE in conjunction with HD-WLE and NBI enabled the identification of 2 and 1 additional HGD/EC patients compared with HD-WLE and HD-WLE or NB!, respectively, resulting in detection of all HGD/EC patients, although not statistically significant. Limitations: Academic centers with enriched population. Conclusions: pCLE combined with HD-WLE significantly improved the ability to detect neoplasia in BE patients compared with HD-WLE. This may allow better informed decisions to be made for the management and subsequent treatment of BE patients. (Clinical trial registration number: NCT00795184.) (Gastrointest Enclose 2011;74:465-72.) C1 [Sharma, Prateek; Bansal, Ajay; Rastogi, Amit; Gupta, Neil] Vet Affairs Med Ctr, Kansas City, MO USA. [Sharma, Prateek; Bansal, Ajay; Rastogi, Amit; Gupta, Neil] Univ Kansas, Sch Med, Kansas City, MO USA. [Meining, Alexander R.; Bajbouj, Monther] Tech Univ Munich, Klinikum Rechts Isar, D-8000 Munich, Germany. [Wolfsen, Herbert C.; Wallace, Michael B.] Mayo Clin, Jacksonville, FL 32224 USA. [Coron, Emmanuel; Wallace, Michael B.] CHU Nantes, F-44035 Nantes 01, France. [Lightdale, Charles J.; Abrams, Julian A.] Columbia Univ, Med Ctr, New York, NY USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Michalek, Joel E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Sharma, P (reprint author), Dept Vet Affairs Med Ctr, 4801 E Linwood Blvd, Kansas City, MO 64128 USA. EM psharma@kumc.edu RI Coron, Emmanuel/K-2415-2015 FU Mauna Kea Technologies FX The study was funded by Mauna Kea Technologies. The following authors disclosed financial relationships relevant to this publication: Dr. Wallace: unrestricted educational grant, Mauna Kea Technologies, Dr. Meining, co-inventor on a patent for another product, study Mauna Kea Technologies. The other authors disclosed no financial relationships relevant to this publication. NR 20 TC 106 Z9 109 U1 1 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD SEP PY 2011 VL 74 IS 3 BP 465 EP 472 DI 10.1016/j.gie.2011.04.004 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 817GV UT WOS:000294660200002 PM 21741642 ER PT J AU Dominitz, JA Ko, CW AF Dominitz, Jason A. Ko, Cynthia W. TI Will colon capsule endoscopy replace screening colonoscopy? SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID SERVICES TASK-FORCE; COLORECTAL-CANCER C1 [Dominitz, Jason A.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Dominitz, JA (reprint author), Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 10 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD SEP PY 2011 VL 74 IS 3 BP 590 EP 592 DI 10.1016/j.gie.2011.06.016 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 817GV UT WOS:000294660200020 PM 21872712 ER PT J AU Lomonaco, R Ortiz-Lopez, C Orsak, B Finch, J Webb, A Bril, F Louden, C Tio, F Cusi, K AF Lomonaco, Romina Ortiz-Lopez, Carolina Orsak, Beverly Finch, Joan Webb, Amy Bril, Fernando Louden, Christopher Tio, Fermin Cusi, Kenneth TI Role of Ethnicity in Overweight and Obese Patients with Nonalcoholic Steatohepatitis SO HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; DEPENDENT DIABETES-MELLITUS; INSULIN-RESISTANCE; HEPATIC STEATOSIS; UNITED-STATES; GLUCOSE; PIOGLITAZONE; POPULATION; PREVALENCE; SECRETION AB The role of ethnicity in determining disease severity in nonalcoholic steatohepatitis (NASH) remains unclear. We recruited 152 patients with biopsy-proven NASH, 63% of whom were Hispanic and 37% of whom were Caucasian. Both groups were well matched for age, sex, and total body fat. We measured: (1) liver fat by magnetic resonance imaging and spectroscopy; (2) fasting plasma glucose, fasting plasma insulin (FPI), and free fatty acid (FFA) levels; (3) total body fat by dual energy x-ray absorptiometry (DXA); (4) liver and muscle insulin sensitivity (insulin clamp with 3-[(3)H] glucose); (5) insulin resistance at the level of the liver (fasting endogenous glucose production derived from 3-[3H] glucose infusion x FPI) and adipose tissue (fasting FFA x FPI). Liver fat was slightly, but not significantly, higher in Hispanic vs. Caucasian patients (27 +/- 2% vs. 24 +/- 2%, p = 0.16). However, this trend did not translate into worse liver steatosis, necroinflammation or fibrosis. Patients with NASH had severe hepatic, adipose tissue and muscle insulin resistance versus healthy subjects without NASH nonalcoholic fatty liver disease, but there were no differences between both ethnic groups on these parameters. However, Hispanics versus Caucasians with type 2 diabetes mellitus (T2DM) had a trend for worse hepatic/adipose tissue insulin resistance and fibrosis. Conclusion: When Hispanic and Caucasian patients with NASH are well matched for clinical parameters, particularly for adiposity, slightly higher liver fat content is not associated with worse hepatic insulin resistance or more severe NASH on histology. Hispanic ethnicity does not appear to be a major determinant of disease severity in NASH, although those with diabetes may be at greater risk of fibrosis. Given the higher risk of T2DM in Hispanics, long-term studies are needed to define their risk of disease progression. (HEPATOLOGY 2011;54:837-845) C1 [Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Vet Adm Med Ctr, Dept Med, Diabet Div, San Antonio, TX 78229 USA. [Webb, Amy] Univ Texas Hlth Sci Ctr San Antonio, Div Hepatol, San Antonio, TX 78229 USA. [Louden, Christopher] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Tio, Fermin] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Cusi, K (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Audie L Murphy Vet Adm Med Ctr, Dept Med, Diabet Div, San Antonio, TX 78229 USA. EM cusi@uthscsa.edu RI webb, andrew/G-9642-2016 FU Burroughs Wellcome Fund; American Diabetes Association [1-08-CR-08]; VA Merit Award [1 101 CX000167-01]; Veterans Affairs Medical Research Fund; National Center for Research Resources [UL IRR025767] FX Supported by the Burroughs Wellcome Fund (K. C.), the American Diabetes Association (1-08-CR-08 [K. C.]), and a VA Merit Award (1 101 CX000167-01 [K. C.]). Additional support was received from the Veterans Affairs Medical Research Fund and by Award No. UL IRR025767 from the National Center for Research Resources. NR 45 TC 37 Z9 37 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2011 VL 54 IS 3 BP 837 EP 845 DI 10.1002/hep.24483 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 818FZ UT WOS:000294738300012 PM 21674556 ER PT J AU Grande, LJ Rudolph, JL Milberg, WP Barber, CE McGlinchey, RE AF Grande, Laura J. Rudolph, James L. Milberg, William P. Barber, Colleen E. McGlinchey, Regina E. TI Detecting cognitive impairment in individuals at risk for cardiovascular disease: the "Clock-in-the-Box" screening test SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE clock drawing; cognitive screening; cardiovascular; executive function; memory ID ALZHEIMERS-DISEASE; HYPERINTENSITIES; RELIABILITY; PERFORMANCE; DEMENTIA; VOLUMES AB Objective: The purpose of this study was to evaluate the performance on the Clock-in-the-Box (CIB), a screening measure for cognitive function, relative to neuropsychological testing in an older population with cardiovascular risk. Methods: A prospective cohort of older patients (>50 years) with cardiovascular risk was recruited to perform the CIB and complete a brief neuropsychological battery consisting of Trailmaking tests, the Hopkins Verbal Learning Test (HVLT), and fluency tasks. Performance on the CIB was scored according to standard criteria (range 0-8, 0-worst). The performance on the total CIB, working memory subscale (CIB-WM), and planning/organization (COB-PO) was compared to neuropsychological measures. Results: The cohort (n = 127) was older (age 67 +/- 7 years) and diverse with 33% female (n = 42) and 42% non-white race (n = 53). Cardiac risk factors were prevalent: hypertension (83%), hyperlipidemia (74%), overweight (84%), diabetes (48%), prior cardiac disease (39%), and smoking (11%). The CIB (mean 6.5 +/- 1.3) took 84 +/- 21 s on average to complete and had good inter-rater reliability (kappa = 0.809, p < 0.01). The CIB-WM subscale was significantly correlated with performance on Trailmaking B and HVLT learning, recall, and recognition. The CIB-PO subscale was significantly associated with semantic and phonemic fluency, Trailmaking B, and HVLT learning and recall. In regression modeling, CIB-WM significantly predicted performance on HVLT learning, recall, and retention. CIB-PO subscale predicted performance on Trailmaking B, HVLT learning, and HVLT recall. Conclusions: The CIB is a brief cognitive screening instrument with good reliability and predictive validity in a CV risk population. The CIB-WM and CIB-PO subscales could provide utility for clinicians. Published in 2010 by John Wiley & Sons, Ltd. C1 [Grande, Laura J.; Rudolph, James L.; Milberg, William P.; Barber, Colleen E.; McGlinchey, Regina E.] Boston VA Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA 02130 USA. [Grande, Laura J.; Milberg, William P.; McGlinchey, Regina E.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rudolph, James L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Rudolph, JL (reprint author), Boston VA Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA 02130 USA. EM jrudolph@partners.org RI McGlinchey, Regina/R-1971-2016 FU National Institutes of Health, Claude Pepper Older American Independence Center [5P60 AG0 8812, R03AG029861-02]; Institutional National Research Service [T32-AG023480]; VA Rehabilitation Career Development Award FX This work was supported by pilot grants from National Institutes of Health, Claude Pepper Older American Independence Center (5P60 AG0 8812), R03AG029861-02, and an Institutional National Research Service Award (T32-AG023480). Dr. Rudolph is funded by a VA Rehabilitation Career Development Award. NR 25 TC 7 Z9 7 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD SEP PY 2011 VL 26 IS 9 BP 969 EP 975 DI 10.1002/gps.2635 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 815YZ UT WOS:000294567200013 PM 21845599 ER PT J AU Brunoni, AR Amadera, J Berbel, B Volz, MS Rizzerio, BG Fregni, F AF Brunoni, Andre Russowsky Amadera, Joao Berbel, Bruna Volz, Magdalena Sarah Rizzerio, Brenno Gomes Fregni, Felipe TI A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Adverse effects; brain stimulation; meta-analysis; systematic review; transcranial direct current stimulation ID NONINVASIVE BRAIN-STIMULATION; HUMAN MOTOR CORTEX; DOUBLE-BLIND; PREFRONTAL CORTEX; DC STIMULATION; ELECTRICAL-STIMULATION; HYPOMANIC EPISODE; MAJOR DEPRESSION; DRUG-REACTIONS; CHRONIC PAIN AB Transcranial direct current stimulation (tDCS) is a non-invasive method of brain stimulation that has been intensively investigated in clinical and cognitive neuroscience. Although the general impression is that tDCS is a safe technique with mild and transient adverse effects (AEs), human data on safety and tolerability are largely provided from single-session studies in healthy volunteers. In addition the frequency of AEs and its relationship with clinical variables is unknown. With the aim of assessing tDCS safety in different conditions and study designs, we performed a systematic review and meta-analysis of tDCS clinical trials. We assessed Medline and other databases and reference lists from retrieved articles, searching for articles from 1998 (first trial with contemporary tDCS parameters) to August 2010. Animal studies, review articles and studies assessing other neuromodulatory techniques were excluded. According to our eligibility criteria, 209 studies (from 172 articles) were identified. One hundred and seventeen studies (56%) mentioned AEs in the report. Of these studies, 74 (63%) reported at least one AE and only eight studies quantified AEs systematically. In the subsample reporting AEs, the most common were, for active vs. sham tDCS group, itching (39.3% vs. 32.9%, p>0.05), tingling (22.2% vs. 18.3%, p>0.05), headache (14.8% vs. 16.2%, p>0.05), burning sensation (8.7% vs. 10%, p>0.05) and discomfort (10.4% vs. 13.4%, p>0.05). Meta-analytical techniques could be applied in only eight studies for itching, but no definite results could be obtained due to between-study heterogeneity and low number of studies. Our results suggested that some AEs such as itching and tingling were more frequent in the tDCS active group, although this was not statistically significant. Although results suggest that tDCS is associated with mild AEs only, we identified a selective reporting bias for reporting, assessing and publishing AEs of tDCS that hinders further conclusions. Based on our findings, we propose a revised adverse effects questionnaire to be applied in tDCS studies in order to improve systematic reporting of tDCS-related AEs. C1 [Brunoni, Andre Russowsky; Amadera, Joao; Berbel, Bruna; Volz, Magdalena Sarah; Rizzerio, Brenno Gomes; Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil,Lab Neuromodulat, Boston, MA 02114 USA. [Brunoni, Andre Russowsky; Amadera, Joao; Berbel, Bruna; Volz, Magdalena Sarah; Rizzerio, Brenno Gomes; Fregni, Felipe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brunoni, Andre Russowsky; Fregni, Felipe] Univ Sao Paulo, Inst Psychol, Dept Neurosci & Behav, Sao Paulo, Brazil. [Brunoni, Andre Russowsky] Univ Sao Paulo, Univ Hosp, Ctr Pesquisas Clin, Sao Paulo, Brazil. RP Fregni, F (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil,Lab Neuromodulat, 125 Nashua St,727, Boston, MA 02114 USA. EM fregni.felipe@mgh.harvard.edu RI Brunoni, Andre/H-8394-2012 OI Brunoni, Andre/0000-0002-6310-3571 FU German Academic Exchange Service (DAAD) FX M.S.V. is funded by a grant scholarship from German Academic Exchange Service (DAAD). NR 46 TC 195 Z9 207 U1 11 U2 58 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD SEP PY 2011 VL 14 IS 8 BP 1133 EP 1145 DI 10.1017/S1461145710001690 PG 13 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 815XY UT WOS:000294564500011 PM 21320389 ER PT J AU Tucker, EJ Compton, AG Calvo, SE Thorburn, DR AF Tucker, Elena J. Compton, Alison G. Calvo, Sarah E. Thorburn, David R. TI The Molecular Basis of Human Complex I Deficiency SO IUBMB LIFE LA English DT Review DE mitochondrial disorders; molecular genetics; mitochondria; human molecular disease ID RESPIRATORY-CHAIN DISORDERS; MITOCHONDRIAL-DNA MUTATIONS; LEIGH-SYNDROME; ASSEMBLY FACTOR; DISEASE; SUBUNIT; ENCEPHALOPATHY; CHAPERONE; CHILDREN; INVOLVEMENT AB Disorders of oxidative phosphorylation (OXPHOS) have a birth prevalence of similar to 1/5,000 and are the most common inborn errors of metabolism. The most common OXPHOS disorder is complex I deficiency. Patients with complex I deficiency present with variable symptoms, such as muscle weakness, cardiomyopathy, developmental delay or regression, blindness, seizures, failure to thrive, liver dysfunction or ataxia. Molecular diagnosis of patients with complex I deficiency is a challenging task clue to the clinical heterogeneity of patients and the large number of candidate disease genes, both nuclear-encoded and mitochondria! DNA (mtDNA)-encoded. In this review, we have thoroughly surveyed the literature to identify 149 patients described with both isolated complex 1 deficiency and pathogenic mutations within nuclear genes. In total, 115 different pathogenic mutations have been reported in 22 different nuclear genes encoding complex I subunits or assembly factors, highlighting the allelic and locus heterogeneity of this disorder. Missense mutations predominate in genes encoding core subunits and some assembly factors while null-type mutations are common in the genes encoding supernumerary subunits and other assembly factors. Despite developments in molecular technology, many patients do not receive molecular diagnosis and no gene has yet been identified that accounts for more than 5% of cases, suggesting that there are likely many disease genes that await discovery. (C) 2011 IUBMB IUBMB Life, 63(9): 669-677, 2011 C1 [Tucker, Elena J.; Compton, Alison G.; Thorburn, David R.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Tucker, Elena J.; Thorburn, David R.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia. [Calvo, Sarah E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Calvo, Sarah E.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Calvo, Sarah E.] Broad Inst, Cambridge, MA USA. [Thorburn, David R.] Royal Childrens Hosp, Genet Hlth Serv Victoria, Melbourne, Vic, Australia. RP Tucker, EJ (reprint author), Royal Childrens Hosp, Murdoch Childrens Res Inst, Flemington Rd, Parkville, Vic 3052, Australia. EM ejtucker@student.unimelb.edu.au RI Tucker, Elena/B-3487-2012; Thorburn, David/G-6266-2013; OI thorburn, david/0000-0002-7725-9470; Compton, Alison/0000-0002-2725-7055 FU Australian National Health and Medical Research Council (NHMRC); NHMRC; Australian Postgraduate Award FX The authors thank Prof. V. Mootha for his helpful feedback on this manuscript and for collaboration in the Mito study that prompted this invited review. The authors' work is supported by grants from the Australian National Health and Medical Research Council (NHMRC). DRT is supported by an NHMRC Principal Research Fellowship and EJT by an Australian Postgraduate Award. NR 50 TC 23 Z9 24 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD SEP PY 2011 VL 63 IS 9 BP 669 EP 677 DI 10.1002/iub.495 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 817FZ UT WOS:000294658000001 PM 21766414 ER PT J AU Connick, E Bosch, RJ Aga, E Schlichtemeier, R Demeter, LM Volberding, P AF Connick, Elizabeth Bosch, Ronald J. Aga, Evgenia Schlichtemeier, Rick Demeter, Lisa M. Volberding, Paul CA ACTG 709 Team TI Augmented HIV-Specific Interferon-Gamma Responses, But Impaired Lymphoproliferation During Interruption of Antiretroviral Treatment Initiated in Primary HIV Infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4-positive T lymphocytes; CD8-positive T lymphocytes; cytotoxic T lymphocytes; HIV infections; highly active antiretroviral therapy; treatment interruption ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; VIRAL REPLICATION; IMMUNE-RESPONSES; THERAPY; INDIVIDUALS; VIREMIA; TRIALS; IMMUNIZATION; ANTIGENS AB Background: Antiretroviral therapy (ART) introduced during primary HIV infection followed by treatment interruption (TI) is postulated to enhance virologic control through induction of HIV-specific CD4(+) T cells, which foster virus-specific CD8+ T cells that suppress virus replication. This hypothesis was evaluated in 21 subjects enrolled in AIDS Clinical Trials Group 709, a substudy of AIDS Clinical Trials Group 371, which prospectively evaluated subjects who received >= 1 year of ART initiated in acute or recent HIV infection followed by TI. Methods: Lymphoproliferation was assessed by [methyl-(3)H] thymidine incorporation and HIV-specific CD8+ T-cell interferon-gamma responses by enzyme-linked immunospot-forming assays. Virologic success was defined as sustained viral load <5000 copies per milliliter for 24 weeks after TI. Results: HIV-specific lymphoproliferative responses were detected at least once in 5 (24%) of 21 subjects, were generally transient, and were unrelated to HIV-specific interferon-gamma responses (P>0.4). HIV-specific CD8+ interferon-gamma responses increased after 48 weeks of ART (P = 0.03), but failed to predict virologic success (P = 0.18). Compared with seronegative subjects, lymphoproliferation to Candida, cytomegalovirus, and alloantigens was similar in HIV-infected subjects during ART, but lower during TI (P <= 0.04). Conclusions: HIV-specific CD8+ T-cell interferon-gamma responses expand during ART following primary HIV infection, but are not related to HIV-specific lymphoproliferative responses norvirologic success. Impaired non-HIV antigen-specific lymphoproliferation associated with TI suggests this strategy could be deleterious. C1 [Connick, Elizabeth; Schlichtemeier, Rick] Univ Colorado Denver, Dept Med, Div Infect Dis, Aurora, CO 80045 USA. [Bosch, Ronald J.; Aga, Evgenia] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Demeter, Lisa M.] Univ Rochester, Sch Med & Dent, Dept Med, Div Infect Dis, Rochester, NY 14642 USA. [Volberding, Paul] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Volberding, Paul] San Francisco Vet Adm Med Ctr, San Francisco, CA USA. RP Connick, E (reprint author), Univ Colorado Denver, Dept Med, Div Infect Dis, 12700 E 19th Ave,Box B168, Aurora, CO 80045 USA. EM liz.connick@ucdenver.edu FU AIDS Clinical Trials Group, under the National Institute of Allergy and Infectious Diseases [AI-68636, AI-38858, AI 69450, AI-38855, AI-069511, AI-69432, AI-68634] FX Supported by the AIDS Clinical Trials Group, under the National Institute of Allergy and Infectious Diseases grants AI-68636, AI-38858, AI 69450, AI-38855, AI-069511, AI-69432, and AI-68634. In addition, study drugs were provided by the manufacturers including GlaxoSmithKline, Bristol Myers Squibb, Agouron/Pfizer. NR 36 TC 2 Z9 2 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 SEP 1 PY 2011 VL 58 IS 1 BP 1 EP 8 DI 10.1097/QAI.0b013e318224d0c7 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 816OA UT WOS:000294610600006 PM 21637110 ER PT J AU Beck, D Niessner, H Flaherty, K Vasseur, S Iovanna, JL Bauer, J Weide, B Kulms, D Schadendorf, D Garbe, C Meier, F AF Beck, D. Niessner, H. Flaherty, K. Vasseur, S. Iovanna, J. L. Bauer, J. Weide, B. Kulms, D. Schadendorf, D. Garbe, C. Meier, F. TI The BRAFV600E kinase inhibitor vemurafenib induces endoplasmic reticulum stress-mediated apoptosis in BRAFV600E mutated melanoma cells SO JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT LA English DT Meeting Abstract C1 [Beck, D.; Niessner, H.; Bauer, J.; Weide, B.; Garbe, C.; Meier, F.] Univ Hautklin, Tubingen, Germany. [Flaherty, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vasseur, S.; Iovanna, J. L.] Ctr Rech INSERM, Marseille, France. [Kulms, D.] Univ Stuttgart, Inst Cell Biol & Immunol, Stuttgart, Germany. [Schadendorf, D.] Univ Essen Gesamthsch, Dept Dermatol, Essen, Germany. RI Kulms, Dagmar/H-1653-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1610-0379 J9 J DTSCH DERMATOL GES JI J. Dtsch. Dermatol. Ges. PD SEP PY 2011 VL 9 IS 9 BP 792 EP 792 PG 1 WC Dermatology SC Dermatology GA 816KH UT WOS:000294596900180 ER PT J AU Vorhies, JS Wang, Y Herndon, J Maloney, W Huddleston, JI AF Vorhies, John S. Wang, Yun Herndon, James Maloney, Williaml Huddleston, James I. TI Readmission and Length of Stay After Total Hip Arthroplasty in a National Medicare Sample SO JOURNAL OF ARTHROPLASTY LA English DT Article DE length of hospital stay; total hip arthroplasty; medicare AB Evaluation of hospital readmissions after total hip arthroplasty may help improve patient safety and cost reduction. This study investigates the rates and reasons for readmission as well as length of hospital stay (LOS) for 1802 total hip arthroplasty patients from 2002 to 2007. Data were abstracted from the Medicare Patient Safety Monitoring System. The overall 30-day rate of readmission was 6.8%. There was no difference in readmission rate from 2002 to 2004 (7.1%) to 2005 to 2007 (6.3%) (odds ratio, 0.90; 95% confidence interval, 0.63-1.30; P = .58). The overall mean LOS was 4.2 +/- 2.2 days. There was a significant reduction in LOS from 2002 to 2004 (4.4 +/- 2.5 days) to 2005 to 2007 (3.8 +/- 1.7 days) (odds ratio, 1.28; 95% confidence interval, 1.25-1.31; P < .0001). The most common causes for readmission were cardiac related. A reduction in LOS was not associated with an increase in the rate of readmission in this sample. Efforts to optimize cardiac status before discharge may lead to lower rates of readmission in the future. C1 [Vorhies, John S.; Maloney, Williaml; Huddleston, James I.] Stanford Univ, Med Ctr, Dept Orthopaed Surg, Stanford, CA 94305 USA. [Herndon, James] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Huddleston, JI (reprint author), Stanford Med Outpatient Ctr, Dept Orthopaed Surg, 450 Broadway St,Mailcode 6324, Redwood City, CA 94063 USA. NR 22 TC 46 Z9 46 U1 0 U2 2 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 SEP PY 2011 VL 26 IS 6 SU 1 BP 119 EP 123 DI 10.1016/j.arth.2011.04.036 PG 5 WC Orthopedics SC Orthopedics GA 813TL UT WOS:000294393000023 PM 21723700 ER PT J AU Malchau, H Bragdon, CR Muratoglu, OK AF Malchau, Henrik Bragdon, Charles R. Muratoglu, Orhun K. TI The Stepwise Introduction of Innovation into Orthopedic Surgery The Next Level of Dilemmas SO JOURNAL OF ARTHROPLASTY LA English DT Article DE introduction of innovation; complexity of innovation; complexity of introduction ID TOTAL HIP-ARTHROPLASTY; CROSS-LINKED POLYETHYLENE; MOLECULAR-WEIGHT POLYETHYLENE; 6-YEAR FOLLOW-UP; FEMORAL COMPONENT; ACETABULAR COMPONENTS; MECHANICAL-PROPERTIES; 3RD-BODY WEAR; MINIMUM; CEMENT AB The optimum method for the appropriate introduction of innovative technologies into orthopedics is a vital but vexing issue. Compromises in the introduction process are driven by (a) the magnitude of the problem addressed (incidence and severity), (b) the advantages and risks of the proposed solution, and (c) the "universal dilemma," meaning the inherent "gap" between all the nonhuman supporting data and the unknowns of both efficacy and long-term safety in large human usage over many years. Drawing on the data generated and the actual decision tree used in the introduction of a new highly cross-linked polyethylene as a case study, this article illustrates these "subsequent dilemmas." C1 [Malchau, Henrik; Bragdon, Charles R.; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. RP Malchau, H (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Fruit St,Jackson Bldg,Room 1126, Boston, MA 02114 USA. FU William H Harris Foundation; Zimmer, Inc; Biomet International FX Supported by the William H Harris Foundation.; Benefits or funds were received in partial or total support of the research material described in this article. These benefits or support were received from the following sources: Royalties received from Zimmer, Inc and Biomet International. NR 48 TC 21 Z9 21 U1 0 U2 2 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 SEP PY 2011 VL 26 IS 6 BP 825 EP 831 DI 10.1016/j.arth.2010.08.007 PG 7 WC Orthopedics SC Orthopedics GA 813TK UT WOS:000294392900001 PM 20888183 ER PT J AU Hariri, S York, SC O'Connor, MI Parsley, BS McCarthy, JC AF Hariri, Sanaz York, Sally C. O'Connor, Mary I. Parsley, Brian S. McCarthy, Joseph C. TI A Resident Survey Study of Orthopedic Fellowship Specialty Decision Making and Views on Arthroplasty as a Career SO JOURNAL OF ARTHROPLASTY LA English DT Article DE resident; career decision making; arthroplasty; fellowship AB A dramatic shortage of total hip arthroplasty (THA) and total knee arthroplasty (TKA) surgeons has been projected because fewer residents enter arthroplasty fellowships, and the demand for THAs/TKAs is rising. The purposes of this study were to ascertain the future supply of THA/TKA surgeons, to identify the criteria residents use to choose their fellowship specialty, and to assess resident perceptions of an arthroplasty career. Four hundred ninety-eight post-graduate year 3 and above residents completed the online survey. Residents most highly prioritize intellectual factors and role models/mentors in determining their fellowship specialty. In the face of a looming patient access-to-care crisis, the data from this study support a policy of highlighting the intellectual challenges and satisfaction of THA/TKA as a career and encouraging mentorship early in a resident's training. C1 [Hariri, Sanaz] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. [York, Sally C.] Univ Washington, Clin Fac, Nursing Program, Tacoma, WA USA. [O'Connor, Mary I.] Mayo Clin, Dept Orthoped Surg, Jacksonville, FL 32224 USA. [Parsley, Brian S.] Baylor Coll Med, Houston, TX 77030 USA. [McCarthy, Joseph C.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. [McCarthy, Joseph C.] Newton Wellesley Hosp, Kaplan Ctr Joint Reconstruct Surg, Newton, MA USA. RP Hariri, S (reprint author), 555 Knowles Dr,Suite 200, Los Gatos, CA 95032 USA. FU AAHKS FX The authors thank Heidi Schmalz (AAOS survey research manager) for fine-tuning the survey and posting it online in an efficient and professional format, and AAHKS for funding this study and for establishing the Health Policy Fellowship program in 2008. Dr. Hariri was the first AAHKS health policy fellow, and this survey study was her thesis. NR 20 TC 6 Z9 6 U1 0 U2 2 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 SEP PY 2011 VL 26 IS 6 BP 961 EP 968 DI 10.1016/j.arth.2010.09.012 PG 8 WC Orthopedics SC Orthopedics GA 813TK UT WOS:000294392900023 PM 21130602 ER PT J AU Stoddard, FJ White, GW Kazis, LE Murphy, JM Sorrentino, EA Hinson, M Stubbs, TK Chan, G Sheridan, RL Palmieri, T Kagan, R Herndon, D Tompkins, RG AF Stoddard, Frederick J., Jr. White, Gwyne W. Kazis, Lewis E. Murphy, J. Michael Sorrentino, Erica A. Hinson, Michelle Stubbs, Teresa Kim Chan, Grace Sheridan, Robert L. Palmieri, Tina Kagan, Richard Herndon, David Tompkins, Ronald G. TI Patterns of Medication Administration From 2001 to 2009 in the Treatment of Children With Acute Burn Injuries: A Multicenter Study SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; YOUNG-CHILDREN; ACUTE MORPHINE; ADOLESCENTS; MANAGEMENT; PTSD; PREVENTION; SYMPTOMS; PROPOFOL; ANXIETY AB Children with burn injuries receive a broad range of medications, from analgesics to antipsychotics, but how utilization of these drugs differs from one pediatric burn center to another is unclear. This study examined utilization patterns of six categories of medication administered acutely to burned children as a first step in creating evidence-based practice guidelines. Six medications administered to pediatric patients enrolled in a multicenter study were recorded from patient charts using a standardized chart review template. The medication categories included opiates, benzodiazepines, antidepressants, beta-blockers, two different anesthetics, and antipsychotics. Data were analyzed by chi(2) and logistical regression analysis. Analysis of data from three sites and 470 patients revealed significant differences in prescription patterns across hospitals for all medication groups except opiates. Differences were significant for benzodiazepines and antidepressants (chi(2) = 7.3; P < .01 for both) controlling for age, gender, race, language, burn size, and length of stay. Differences in prescribing patterns for beta-blockers and the anesthetics ketamine and propofol failed to reach statistical significance; however, the results did trend in that direction (chi(2) = 3.8 and 3.4, respectively; P < .10 for both). The pharmacotherapeutic agents described in this study are an integral part of acute pediatric burn care, and yet there is variation in use of these medications among the centers. The differences in prescribing indicate that, for certain drugs, a range of approaches to pharmacotherapeutics is being used and suggest that evidence-based guidelines for administration of these agents need to be developed. (J Burn Care Res 2011;32:519-528) C1 [Stoddard, Frederick J., Jr.; White, Gwyne W.; Murphy, J. Michael; Sorrentino, Erica A.; Sheridan, Robert L.; Tompkins, Ronald G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Stoddard, Frederick J., Jr.; White, Gwyne W.; Kazis, Lewis E.; Murphy, J. Michael; Sorrentino, Erica A.; Hinson, Michelle; Sheridan, Robert L.; Tompkins, Ronald G.] Shriners Hosp Children, Boston, MA USA. [Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, CAPP, Boston, MA 02215 USA. [Stubbs, Teresa Kim; Kagan, Richard] Shriners Hosp Children, Cincinnati, OH USA. [Chan, Grace; Palmieri, Tina] Shriners Hosp Children No Calif, Sacramento, CA USA. [Herndon, David] Shriners Hosp Children, Galveston, TX 77550 USA. RP Stoddard, FJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, SBH 610,55 Fruit St, Boston, MA 02114 USA. OI Kazis, Lewis/0000-0003-1800-5849 FU Shriners Hospitals for Children [9157] FX Supported by Grant # 9157 from the Shriners Hospitals for Children. NR 30 TC 6 Z9 6 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD SEP-OCT PY 2011 VL 32 IS 5 BP 519 EP 528 DI 10.1097/BCR.0b013e31822bef92 PG 10 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 817PW UT WOS:000294687300006 PM 21811176 ER PT J AU Klubo-Gwiezdzinska, J Manes, RP Chia, SH Burman, KD Stathatos, NA Deeb, ZE Wartofsky, L AF Klubo-Gwiezdzinska, Joanna Manes, R. Peter Chia, Stanley H. Burman, Kenneth D. Stathatos, Nikolaos A. Deeb, Ziad E. Wartofsky, Leonard TI Ectopic Cervical Thyroid Carcinoma-Review of the Literature with Illustrative Case Series SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID THYROGLOSSAL DUCT CARCINOMA; BRANCHIAL CLEFT CYST; UPPER AIRWAY-OBSTRUCTION; LYMPH-NODE METASTASES; MISSED PRIMARY TUMOR; LATERAL NECK CYST; PAPILLARY CARCINOMA; TISSUE; MANAGEMENT; GLAND AB Context: More than 99% of thyroid cancers arise eutopically within the thyroid gland. The most frequent sites of ectopic thyroid tissue are lingual, sublingual, thyroglossal, laryngotracheal, and lateral cervical. Thyroid tissue can also be found in remote structures that were associated with the thyroid anlage during development, including the esophagus, mediastinum, heart, aorta, adrenal, pancreas, gallbladder, and skin. Ectopic thyroid tissue can be subject to the same pathological processes as normal eutopic thyroid tissue such as inflammation, hyperplasia, and tumorigenesis. The aim of this review is to describe aspects of thyroid cancer arising from the ectopic thyroid tissue in the neck in regard to epidemiology, diagnosis, and treatment and to present an illustrative series of cases of ectopic thyroid cancer. Data Acquisition: We have searched the PubMed database for articles including the keywords "ectopic thyroid cancer" published between January 1, 1960, and January 1, 2011. As references, we used clinical case series, case reports, review articles, and practical guidelines focused on ectopic thyroid cancer confined to the neck region. Synthesis and Conclusions: The possibility of an ectopic thyroid cancer should be considered in the differential diagnosis of a pathological mass in the neck. Treatment of ectopic cervical thyroid cancer is based predominantly on the surgical excision of the malignant lesion. Management strategies, including performance of total thyroidectomy, neck dissection, and treatment with radioiodine, should be based on individualized risk stratification. (J Clin Endocrinol Metab 96: 2684-2691, 2011) C1 [Klubo-Gwiezdzinska, Joanna; Burman, Kenneth D.] Washington Hosp Ctr, Dept Endocrinol, Washington, DC USA. [Manes, R. Peter] Yale Univ, Sch Med, Dept Surg, Sect Otolaryngol Head & Neck Surg, New Haven, CT 06519 USA. [Chia, Stanley H.; Deeb, Ziad E.] Georgetown Univ Hosp, Dept Otolaryngol Head & Neck Surg, Washington, DC 20007 USA. [Stathatos, Nikolaos A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Klubo-Gwiezdzinska, Joanna] Nicolaus Copernicus Univ Torun, Coll Med Bydgoszcz, PL-85091 Bydgoszcz, Poland. [Wartofsky, Leonard] Washington Hosp Ctr, Dept Med, Washington, DC 20010 USA. RP Wartofsky, L (reprint author), Washington Hosp Ctr, Dept Med, 110 Irving St NW, Washington, DC 20010 USA. EM leonard.wartofsky@medstar.net NR 78 TC 18 Z9 18 U1 0 U2 4 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 SEP PY 2011 VL 96 IS 9 BP 2684 EP 2691 DI 10.1210/jc.2011-0611 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 815VR UT WOS:000294558600037 PM 21752893 ER PT J AU Vongpatanasin, W Kario, K Atlas, SA Victor, RG AF Vongpatanasin, Wanpen Kario, Kazuomi Atlas, Steven A. Victor, Ronald G. TI Central Sympatholytic Drugs SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Review ID MODERATE ESSENTIAL-HYPERTENSION; SYNDROME FOLLOWING CESSATION; PLASMA-RENIN ACTIVITY; BLOOD-PRESSURE; CLINICAL PHARMACOKINETICS; THERAPEUTIC EFFICACY; WITHDRAWAL SYNDROME; CLONIDINE; GUANFACINE; METHYLDOPA AB Key Points Central sympatholytic drugs reduce blood pressure mainly by stimulating central alpha(2)-adrenergic receptors in the brainstem centers, thereby reducing sympathetic nerve activity and neuronal release of norepinephrine to the heart and peripheral circulation. This class of drugs, however, is currently used mainly as fourth-line (or beyond) drug therapy for hypertension because of side effects of drowsiness, fatigue, and dry mouth. Rebound hypertension is also another major concern in certain drugs with a short half-life, particularly in patients who are nonadherent to the regimen. Therefore, their use on a "PRN" basis for treatment of blood pressure surge in the absence of symptoms or acute target complications should also be avoided. J Clin Hypertens (Greenwich). 2011; 13: 658-661. (C)2011 Wiley Periodicals, Inc. C1 [Vongpatanasin, Wanpen] Univ Texas SW Med Ctr Dallas, Div Cardiol, Hypertens Sect, Dallas, TX 75390 USA. [Kario, Kazuomi] Jichi Med Univ, Sch Med, Dept Med, Div Cardiovasc Med, Shimotsuke, Tochigi, Japan. [Atlas, Steven A.] Mt Sinai Sch Med, James J Peters VA Med Ctr, Bronx, NY USA. [Atlas, Steven A.] Mt Sinai Sch Med, Dept Med, Bronx, NY USA. [Victor, Ronald G.] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA. RP Vongpatanasin, W (reprint author), Univ Texas SW Med Ctr Dallas, Div Cardiol, Hypertens Sect, 5323 Harry Hines Blvd,U9-400, Dallas, TX 75390 USA. EM wanpen.vongpatanasin@utsouthwestern.edu NR 36 TC 10 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD SEP PY 2011 VL 13 IS 9 BP 658 EP 661 DI 10.1111/j.1751-7176.2011.00509.x PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 816KD UT WOS:000294596300006 PM 21896146 ER PT J AU Weir, GC Bonner-Weir, S AF Weir, Gordon C. Bonner-Weir, Susan TI Finally! A human pancreatic beta cell line SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID INSULIN-SECRETION; RAT; ESTABLISHMENT; LANGERHANS; EXPRESSION; ISLETS; TUMOR AB For decades, investigators have made numerous attempts to generate human pancreatic beta cell lines that could be used to advance beta cell biology, facilitate drug discovery, and provide a pathway to beta cell replacement therapy for the treatment of diabetes. In this issue of the JCI, Ravassard and colleagues report that this has finally been achieved successfully with a multistep process that led to the generation of cells, which they termed EndoC-beta H1 cells, that secreted insulin in response to glucose challenge. C1 [Weir, Gordon C.] Joslin Diabet Ctr, Div Res, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Cell Biol & Regenerat Med, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836, R01 DK066056, RC4 DK090781] NR 17 TC 4 Z9 4 U1 0 U2 3 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 SEP PY 2011 VL 121 IS 9 BP 3395 EP 3397 DI 10.1172/JCI58899 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 818LR UT WOS:000294753700009 PM 21865653 ER PT J AU Wu, JY Aarnisalo, P Bastepe, M Sinha, P Fulzele, K Selig, MK Chen, M Poulton, IJ Purton, LE Sims, NA Weinstein, LS Kronenberg, HM AF Wu, Joy Y. Aarnisalo, Piia Bastepe, Murat Sinha, Partha Fulzele, Keertik Selig, Martin K. Chen, Min Poulton, Ingrid J. Purton, Louise E. Sims, Natalie A. Weinstein, Lee S. Kronenberg, Henry M. TI G(s)alpha enhances commitment of mesenchymal progenitors to the osteoblast lineage but restrains osteoblast differentiation in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PARATHYROID-HORMONE; BONE-FORMATION; BETA-CATENIN; CHONDROCYTE DIFFERENTIATION; INTERMITTENT PTH; PROTEIN-KINASE; CELL-LINE; GS-ALPHA; RECEPTOR; OSTEOCYTES AB The heterotrimeric G protein subunit G(s)alpha stimulates cAMP-dependent signaling downstream of G protein-coupled receptors. In this study, we set out to determine the role of G(s)alpha signaling in cells of the early osteoblast lineage in vivo by conditionally deleting G(s)alpha from osterix-expressing cells. This led to severe osteoporosis with fractures at birth, a phenotype that was found to be the consequence of impaired bone formation rather than increased resorption. Osteoblast number was markedly decreased and osteogenic differentiation was accelerated, resulting in the formation of woven bone. Rapid differentiation of mature osteoblasts into matrix-embedded osteocytes likely contributed to depletion of the osteoblast pool. In addition, the number of committed osteoblast progenitors was diminished in both bone marrow stromal cells (BMSCs) and calvarial cells of mutant mice. In the absence of G(s)alpha, expression of sclerostin and dickkopf1 (Dkk1), inhibitors of canonical Wnt signaling, was markedly increased; this was accompanied by reduced Wnt signaling in the osteoblast lineage. In summary, we have shown that G(s)alpha regulates bone formation by at least two distinct mechanisms: facilitating the commitment of mesenchymal progenitors to the osteoblast lineage in association with enhanced Wnt signaling; and restraining the differentiation of committed osteoblasts to enable production of bone of optimal mass, quality, and strength. C1 [Wu, Joy Y.; Aarnisalo, Piia; Bastepe, Murat; Sinha, Partha; Fulzele, Keertik; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Aarnisalo, Piia] Univ Helsinki, Biomedicum Helsinki, Inst Biomed Physiol, Helsinki, Finland. [Aarnisalo, Piia] Univ Helsinki, Dept Clin Chem, SF-00100 Helsinki, Finland. [Aarnisalo, Piia] Helsinki Univ Cent Hosp, Helsinki, Finland. [Selig, Martin K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chen, Min; Weinstein, Lee S.] NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. [Poulton, Ingrid J.; Purton, Louise E.; Sims, Natalie A.] Univ Melbourne, St Vincents Inst, Fitzroy, Vic 3065, Australia. [Poulton, Ingrid J.; Purton, Louise E.; Sims, Natalie A.] Univ Melbourne, St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia. RP Wu, JY (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 1101, Boston, MA 02114 USA. EM jywu@partners.org; hkronenberg@partners.org FU NIH [AR053781, DK117940]; National Institute of Diabetes and Digestive and Kidney Diseases FX We thank David Rowe for providing the Col2.3::GFP transgenic mice; Mark Horowitz for providing the ALP antibody; James Oh, Jackie McConnell, and Rhiannon Chubb for technical assistance; the MGH Center for Comparative Medicine staff for care of the mice; and the Dana Farber Cancer Institute and Harvard Stem Cell Institute flow cytometry cores. This work was supported in part by NIH grants AR053781 (to J.Y. Wu) and DK117940 (to H.M. Kronenberg) and by the National Institute of Diabetes and Digestive and Kidney Diseases' Intramural Research Program (to M. Chen and L.S. Weinstein). NR 67 TC 36 Z9 39 U1 0 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 SEP PY 2011 VL 121 IS 9 BP 3492 EP 3504 DI 10.1172/JCI46406 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 818LR UT WOS:000294753700017 PM 21804192 ER PT J AU Wang, J Cheng, X Xiang, MX Alanne-Kinnunen, M Wang, JA Chen, H He, AN Sun, XH Lin, Y Tang, TT Tu, X Sjoberg, S Sukhova, GK Liao, YH Conrad, DH Yu, LY Kawakami, T Kovanen, PT Libby, P Shi, GP AF Wang, Jing Cheng, Xiang Xiang, Mei-Xiang Alanne-Kinnunen, Mervi Wang, Jian-An Chen, Han He, Aina Sun, Xinghui Lin, Yan Tang, Ting-Ting Tu, Xin Sjoeberg, Sara Sukhova, Galina K. Liao, Yu-Hua Conrad, Daniel H. Yu, Lunyin Kawakami, Toshiaki Kovanen, Petri T. Libby, Peter Shi, Guo-Ping TI IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in Apoe(-/-) mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FC-EPSILON-RI; MEDIATED GENE-TRANSFER; SMOOTH-MUSCLE-CELLS; E-DEFICIENT MICE; SCAVENGER RECEPTOR; APOLIPOPROTEIN-E; MAST-CELLS; REDUCES ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; PROINFLAMMATORY CYTOKINES AB IgE has a key role in the pathogenesis of allergic responses through its ability to activate mast cells via the receptor Fc epsilon R1. In addition to mast cells, many cell types implicated in atherogenesis express Fc epsilon R1, but whether IgE has a role in this disease has not been determined. Here, we demonstrate that serum IgE levels are elevated in patients with myocardial infarction or unstable angina pectoris. We found that IgE and the Fc epsilon R1 subunit Fc epsilon R1 alpha were present in human atherosclerotic lesions and that they localized particularly to macrophage-rich areas. In mice, absence of Fc epsilon R1 alpha reduced inflammation and apoptosis in atherosclerotic plaques and reduced the burden of disease. In cultured macrophages, the presence of TLR4 was required for Fc epsilon R1 activity. IgE stimulated the interaction between Fc epsilon R1 and TLR4, thereby inducing macrophage signal transduction, inflammatory molecule expression, and apoptosis. These IgE activities were reduced in the absence of Fc epsilon R1 or TLR4. Furthermore, IgE activated macrophages by enhancing Na+/H+ exchanger 1 (NHE1) activity. Inactivation of NHE1 blocked IgE-induced macrophage production of inflammatory molecules and apoptosis. Cultured human aortic SMCs (HuSMCs) and ECs also exhibited IgE-induced signal transduction, cytokine expression, and apoptosis. In human atherosclerotic lesions, SMCs and ECs colocalized with IgE and TUNEL staining. This study reveals what we believe to be several previously unrecognized IgE activities that affect arterial cell biology and likely other IgE-associated pathologies in human diseases. C1 [Wang, Jing; Cheng, Xiang; Chen, Han; He, Aina; Sun, Xinghui; Sjoeberg, Sara; Sukhova, Galina K.; Libby, Peter; Shi, Guo-Ping] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wang, Jing; Cheng, Xiang; Chen, Han; He, Aina; Sun, Xinghui; Sjoeberg, Sara; Sukhova, Galina K.; Yu, Lunyin; Libby, Peter; Shi, Guo-Ping] Harvard Univ, Sch Med, Boston, MA USA. [Cheng, Xiang; Tang, Ting-Ting; Liao, Yu-Hua] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Inst Cardiol, Wuhan 430074, Peoples R China. [Xiang, Mei-Xiang; Wang, Jian-An; Chen, Han; Lin, Yan] Zhejiang Univ, Coll Med, Affiliated Hosp 2, Dept Cardiol, Hangzhou 310003, Zhejiang, Peoples R China. [Alanne-Kinnunen, Mervi; Kovanen, Petri T.] Wihuri Res Inst, SF-00140 Helsinki, Finland. [Tu, Xin] Huazhong Univ Sci & Technol, Ctr Human Genome Res, Wuhan 430074, Peoples R China. [Tu, Xin] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China. [Conrad, Daniel H.] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA. [Yu, Lunyin] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kawakami, Toshiaki] La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA USA. RP Shi, GP (reprint author), Brigham & Womens Hosp, Dept Med, 77 Ave Louis Pasteur,NRB 7, Boston, MA 02115 USA. EM gshi@rics.bwh.harvard.edu RI Cheng, Xiang/K-2190-2012; Kawakami, Toshiaki/O-1616-2015; OI yan, wei/0000-0001-5575-7017 FU National Natural Science Foundation of China [30670867, 30871067]; NIH [HL60942, HL81090, HL88547, HL34636, HL80472]; American Heart Association [0840118N] FX This study is supported by grants from the National Natural Science Foundation of China (30670867 to M.X. Xiang; 30871067 to X. Cheng), the NIH (HL60942, HL81090, HL88547 to G.P. Shi; and HL34636, HL80472 to P. Libby), and the American Heart Association Established Investigator Award (0840118N to G.P. Shi). Wihuri Research Institute is maintained by the Jenny and Antti Wihuri Foundation, Helsinki, Finland. NR 58 TC 63 Z9 65 U1 2 U2 22 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 SEP PY 2011 VL 121 IS 9 BP 3564 EP 3577 DI 10.1172/JCI46028 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 818LR UT WOS:000294753700023 PM 21821913 ER PT J AU Vranceanu, AM Ring, D AF Vranceanu, Ana-Maria Ring, David TI Factors Associated With Patient Satisfaction SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Depression; doctor's uneasiness; pain catastrophizing; patient satisfaction ID DEPRESSION; OUTCOMES; CARE AB Purpose This investigation tested the null hypothesis that psychological factors have no effect on patient satisfaction in a hand and upper limb practice. Methods The Center for Epidemiologic Studies Depression Scale, the Pain Catastrophizing Scale, and the Disabilities of the Arm, Shoulder, and Hand questionnaire were administered to 248 new patients presenting to a hand and upper limb practice. After the appointment, the treating physician was asked to rate the patient's uneasiness with his or her symptoms. The Consumer Assessment of Health Care Providers and Systems questionnaire was mailed to patients 2 weeks after their visit. A total of 178 patients returned this questionnaire. Results There were small but significant correlations between (1) depression and perception of how well the doctor (a) listens carefully, (b) gives easy-to-understand instructions, and (c) spends enough time; (2) pain catastrophizing and the degree to which doctor gives enough information about a procedure; and (3) the doctor's perception of inordinate patient concern and (a) the impression that the doctor gives easy-to-understand explanations, (b) the impression that the doctor listens carefully, (c) the impression that the doctor gives enough information about surgical procedures, and (d) the patient's overall rating of the doctor. In multivariable models, the doctor's perception of disproportionate uneasiness was the only significant predictor of "doctor gave enough information" and "doctor listened carefully." Conclusions In this study, the provider's sense that the patient was disproportionately uneasy with his or her symptoms was the only significant predictor of patient satisfaction, and this accounted for a small percentage of the variance in responses to these items. Patient satisfaction is complex, and the divide between medical advice and a patient's expectations are not easily reduced to one or more disease-specific or patient-specific factors. (J Hand Surg 2011;36A:1504-1508. Copyright (C) 2011 by the American Society for Surgery of the Hand. All rights reserved.) Type of study/level of evidence Prognostic II. C1 [Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 15 TC 18 Z9 19 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD SEP PY 2011 VL 36A IS 9 BP 1504 EP 1508 DI 10.1016/j.jhsa.2011.06.001 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 816FV UT WOS:000294585000012 PM 21794990 ER PT J AU Yeo, BTT Krienen, FM Sepulcre, J Sabuncu, MR Lashkari, D Hollinshead, M Roffman, JL Smoller, JW Zoller, L Polimeni, JR Fischl, B Liu, HS Buckner, RL AF Yeo, B. T. Thomas Krienen, Fenna M. Sepulcre, Jorge Sabuncu, Mert R. Lashkari, Danial Hollinshead, Marisa Roffman, Joshua L. Smoller, Jordan W. Zoeller, Lilla Polimeni, Jonathan R. Fischl, Bruce Liu, Hesheng Buckner, Randy L. TI The organization of the human cerebral cortex estimated by intrinsic functional connectivity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE prefrontal; parietal; association cortex; functional magnetic resonance imaging; functional connectivity; default network; connectome ID POSTERIOR PARIETAL CORTEX; HUMAN VISUAL-CORTEX; INDEPENDENT COMPONENT ANALYSIS; CORPUS-CALLOSUM CONNECTIONS; MEDIAL PREFRONTAL NETWORKS; HUMAN INTRAPARIETAL SULCUS; EPISODIC MEMORY RETRIEVAL; BRAINS DEFAULT NETWORK; RESTING-STATE NETWORKS; SURFACE-BASED ANALYSIS AB Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, Roffman JL, Smoller JW, Zollei L, Polimeni JR, Fischl B, Liu H, Buckner RL. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol 106: 11251165, 2011. First published June 8, 2011; doi:10.1152/jn.00338.2011.-Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition. C1 [Yeo, B. T. Thomas; Krienen, Fenna M.; Sepulcre, Jorge; Hollinshead, Marisa; Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Yeo, B. T. Thomas; Krienen, Fenna M.; Sepulcre, Jorge; Sabuncu, Mert R.; Hollinshead, Marisa; Zoeller, Lilla; Polimeni, Jonathan R.; Fischl, Bruce; Liu, Hesheng; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Sepulcre, Jorge; Hollinshead, Marisa; Buckner, Randy L.] Howard Hughes Med Inst, Cambridge, MA USA. [Sabuncu, Mert R.; Lashkari, Danial; Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Roffman, Joshua L.; Smoller, Jordan W.; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Fischl, Bruce] MIT, Harvard Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Buckner, RL (reprint author), Harvard Univ, Dept Psychol, Ctr Brain Sci, 52 Oxford St,Northwest Bldg 280-06, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu RI Polimeni, Jonathan/P-1395-2014; OI Polimeni, Jonathan/0000-0002-1348-1179; Liu, Hesheng/0000-0002-7233-1509; Yeo, B.T. Thomas/0000-0002-0119-3276 FU Department of Defense; Sackler Scholars Program in Psychobiology; National Institutes of Health [AG021910, P41RR14074, K08MH067966, P41RR14075, U24RR021382, AG022381, RC1AT005728, R01NS052585, 1R21NS072652, 1S10RR023401, 1S10RR019, 1S10RR023043, 1R01NS070963]; Massachusetts General Hospital-University of California [U54MH091665]; Ellison Medical Foundation; Howard Hughes Medical Institute; Simons Foundation FX We thank Elizabeth Hemphill, Leah Bakst, and Sara Rubenstein for assistance with data collection; Karl Zilles and Katrin Amunts for the human histological data; Donna Dierker and David Van Essen for help with the Caret software, SumsDB; Doug Greve for help with the FreeSurfer/FsFast software; Simon Eickhoff for help with the SPM Anatomy toolbox; and Avram Holmes, Steve Petersen, Todd Preuss, Roger Tootell, Justin Vincent, and Justin Baker for useful discussion. We thank the Harvard Center for Brain Science Neuroimaging Core and the Athinoula A. Martinos Center for imaging support, and the Harvard Neuroinformatics Research Group (Gabriele Fariello, Timothy O'Keefe, and Victor Petrov). F. M. Krienen was supported by fellowships from the Department of Defense, an Ashford Graduate Fellowship in the Sciences, and the Sackler Scholars Program in Psychobiology.; This work was supported by National Institutes of Health Grants AG021910, P41RR14074, K08MH067966, P41RR14075, U24RR021382, AG022381, RC1AT005728, R01NS052585, 1R21NS072652, 1S10RR023401, 1S10RR019, 1S10RR023043, and 1R01NS070963, the Massachusetts General Hospital-University of California, Los Angeles Human Connectome Project (U54MH091665), the Ellison Medical Foundation, the Howard Hughes Medical Institute, and the Simons Foundation. NR 226 TC 786 Z9 793 U1 25 U2 173 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2011 VL 106 IS 3 BP 1125 EP 1165 DI 10.1152/jn.00338.2011 PG 41 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 818SM UT WOS:000294775500007 PM 21653723 ER PT J AU Miaskowski, C Penko, JM Guzman, D Mattson, JE Bangsberg, DR Kushel, MB AF Miaskowski, Christine Penko, Joanne M. Guzman, David Mattson, Jennifer E. Bangsberg, David R. Kushel, Margot B. TI Occurrence and Characteristics of Chronic Pain in a Community-Based Cohort of Indigent Adults Living With HIV Infection SO JOURNAL OF PAIN LA English DT Article DE HIV; substance use disorders; chronic pain; pain qualities; opioid analgesics ID AMBULATORY AIDS PATIENTS; QUALITY-OF-LIFE; SOCIAL ASSISTANCE RECIPIENTS; CHRONIC NONMALIGNANT PAIN; SAFETY-NET PROVIDERS; LOW-BACK-PAIN; METHADONE-MAINTENANCE; SUBSTANCE-ABUSE; PERIPHERAL NEUROPATHY; ASSESSMENT SCALE AB Pain is common among people living with HIV/AIDS (PLWHA), but little is known about chronic pain in socioeconomically disadvantaged HIV-infected populations with high rates of substance abuse in the postantiretroviral era. This cross-sectional study describes the occurrence and characteristics of pain in a community-based cohort of 296 indigent PLWHA. Participants completed questionnaires about sociodemographics, substance use, depression, and pain. Cut-point analysis was used to generate categories of pain severity. Of the 270 participants who reported pain or the use of a pain medication in the past week, 8.2% had mild pain, 38.1% had moderate pain, and 53.7% had severe pain. Female sex and less education were associated with more severe pain. Depression was more common among participants with severe pain than among those with mild pain. Increasing pain severity was associated with daily pain and with chronic pain. Over half of the participants reported having a prescription for an opioid analgesic. Findings from this study suggest that chronic pain is a significant problem in this high risk, socioeconomically disadvantaged group of patients with HIV disease and high rates of previous or concurrent use of illicit drugs. Perspective: This article presents epidemiological data showing that unrelieved chronic pain is a significant problem for indigent people living with HIV. Participants reported pain severity similar to those with metastatic cancer. Despite high rates of substance use disorders, approximately half received prescriptions for opioid analgesics, although few for long-acting agents. (C) 2011 by the American Pain Society C1 [Kushel, Margot B.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, Dept Internal Med, San Francisco, CA 94143 USA. [Miaskowski, Christine] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Initiat Global Hlth, Boston, MA USA. RP Kushel, MB (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, Dept Internal Med, Box 1364, San Francisco, CA 94143 USA. EM mkushel@medsfgh.ucsf.edu FU NIDA [R01 DA022550]; NIMH [R01 MH054907]; NIH/NCRR UCSF-CTSI [UL1RR024131] FX Funded by NIDA R01 DA022550, NIMH R01 MH054907 and NIH/NCRR UCSF-CTSI grant UL1RR024131. NR 81 TC 37 Z9 38 U1 2 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD SEP PY 2011 VL 12 IS 9 BP 1004 EP 1016 DI 10.1016/j.jpain.2011.04.002 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 819ZZ UT WOS:000294876600007 PM 21684218 ER PT J AU Shah, AA Butler, RB Sung, SY Wells, JH Higgins, LD Warner, JJP AF Shah, Anup A. Butler, Robert B. Sung, Seung-Yong Wells, Jessica H. Higgins, Laurence D. Warner, Jon J. P. TI Clinical outcomes of suprascapular nerve decompression SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Suprascapular nerve decompression; arthroscopic; outcomes ID ROTATOR-CUFF TEARS; VOLLEYBALL PLAYERS; SPINOGLENOID NOTCH; ARTHROSCOPIC RELEASE; GANGLION CYSTS; ENTRAPMENT; NEUROPATHY; SHOULDER; COMPRESSION; PREVALENCE AB Background: While the incidence and prevalence of suprascapular neuropathy (SSN) remains largely unknown, the evaluation and treatment of SSN appears to be increasing. Despite multiple technique articles demonstrating nerve decompression, there has been no clinical evidence to support the efficacy of SSN decompression in the absence of rotator cuff disease. Methods: Between October 2006 and February 2010, 27 patients underwent arthroscopic suprascapular nerve decompression at the suprascapular and/or spinoglenoid notch. Eighty-nine percent (24/27) of patients had preoperative positive electromyography and nerve conduction EMG/NCV studies documenting suprascapular nerve pathology. All patients had either a computed tomography (CT) arthrogram or magnetic resonance imaging (MRI) documenting rotator cuff integrity. All patients were evaluated with pre and postoperative subjective shoulder values (SSV) and American Shoulder and Elbow Society (ASES) self-assessment scores. Additionally, patients were questioned whether they would have the procedure again and approximately at what week they experienced noticeable pain relief. Results: The 27 patients were followed for an average of 22.5 months (range, 3-44). Three patients were lost to follow-up. Seventy-one percent (17/24) of patients reported pain relief (VAS [Visual Analogue Scales] pain scale) that was statistically significant (P = .0001) at an average of 9.4 weeks from surgery. Seventy-five percent (18/24) and 71% (17/24) had statistically significant improvement in ASES (P = .0001) and SSV scores (P = .0014), respectively. Seventy-one percent (17/24) would have the surgery again. Conclusion: The present study demonstrates a large series of patients treated for SSN without rotator cuff pathology. Our results show statistically significant improvement in VAS, ASES, and SSV. Level of evidence: Level IV, Case Series, Treatment Study. (C) 2011 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Shah, Anup A.; Butler, Robert B.; Sung, Seung-Yong; Wells, Jessica H.; Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. [Higgins, Laurence D.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Harvard Shoulder Serv, 55 Fruit St,Yawkey Bldg 3G, Boston, MA 02114 USA. EM jwarner@partners.org NR 47 TC 20 Z9 22 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP PY 2011 VL 20 IS 6 BP 975 EP 982 DI 10.1016/j.jse.2010.10.032 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 818QZ UT WOS:000294771000024 PM 21277808 ER PT J AU Boykin, RE Friedman, DJ Zimmer, ZR Oaklander, AL Higgins, LD Warner, JJP AF Boykin, Robert E. Friedman, Darren J. Zimmer, Zachary R. Oaklander, Anne Louise Higgins, Laurence D. Warner, Jon J. P. TI Suprascapular neuropathy in a shoulder referral practice SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Suprascapular neuropathy; electrodiagnostic testing; massive rotator cuff tear ID ROTATOR-CUFF TEARS; NERVE ENTRAPMENT; SPINOGLENOID LIGAMENT; GANGLION CYSTS; ARTHROSCOPIC RELEASE; VOLLEYBALL PLAYERS; INFRASPINATUS; SUPRASPINATUS; PAIN; DIAGNOSIS AB Hypothesis: Suprascapular neuropathy (SSN) is considered a rare condition, and few studies have analyzed how commonly it is encountered in practice. Electrophysiologic studies are the gold standard for diagnosis; however, there is no consensus on diagnostic criteria. We hypothesized that SSN would be frequently diagnosed by electrophysiologic testing in a subset of patients with specific clinical and radiographic findings suggestive of the pathology. This study characterizes SSN in an academic shoulder referral practice and documents the electrodiagnostic findings that are currently being used to diagnose the condition. Materials and methods: A retrospective review of a 1-year period was used to identify all patients who completed electrodiagnostic studies to evaluate the suprascapular nerve. Clinical exam findings and associated shoulder pathology was documented. The specific electromyography (EMG) and nerve conduction studies (NCS) findings were analyzed. Results: Electrodiagnostic results were available for 92 patients, and 40 (42%) had confirmed SSN. Patients with a massive rotator cuff tear were more likely to have an abnormal study than those without a tear (P = .006). The most common electrodiagnostic abnormalities were abnormal motor unit action potentials (88%), whereas only 33% had evidence of denervation. The average latency in studies reported as diagnostic of SSN was 2.90 +/- 0.08 milliseconds for the supraspinatus and 3.78 +/- 0.14 milliseconds for the infraspinatus. Discussion: An electrodiagnostically confirmed diagnosis of SSN was seen in 4.3% of all new patients and in 43% of patients with clinical or radiographic suspicion of SSN. Clinical evaluation may be difficult because other shoulder pathology can have overlapping symptoms. Conclusion: Shoulder surgeons should consider electrophysiologic evaluation of patients with clinical or radiographic signs of SSN and be cognizant of the parameters that constitute an abnormal study. Level of evidence: Level IV, Case Series. (C) 2011 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. [Friedman, Darren J.] NYU, Sch Med, Dept Orthopaed Surg, NYU Hosp Joint Dis, New York, NY USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Higgins, Laurence D.] Brigham & Womens Hosp, Harvard Shoulder Serv, Boston, MA 02115 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Harvard Shoulder Serv, Yawkey Ctr Outpatient Care, 55 Fruit St,Ste 3200,3G,Rm 3-046, Boston, MA 02114 USA. EM jwarner@partners.org FU National Institutes of Health [NINDS-K24NSO59892] FX This study was supported in part by National Institutes of Health Grant: NINDS-K24NSO59892 (ALO), which was used in data collection and manuscript preparation. The remainder of the funding for the project was internal. NR 40 TC 24 Z9 26 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP PY 2011 VL 20 IS 6 BP 983 EP 988 DI 10.1016/j.jse.2010.10.039 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 818QZ UT WOS:000294771000025 PM 21277806 ER PT J AU Namdari, S Goel, DP Romanowski, J Glaser, D Warner, JJP AF Namdari, Surena Goel, Danny P. Romanowski, James Glaser, David Warner, Jon J. P. TI Principles of glenoid component design and strategies for managing glenoid bone loss in revision shoulder arthroplasty in the absence of infection and rotator cuff tear SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Review ID LATERAL MENISCUS ALLOGRAFT; FINITE-ELEMENT-ANALYSIS; STRESS-ANALYSES; FOLLOW-UP; REPLACEMENT; JOINT; PROSTHESIS; SURVIVAL; REMOVAL; DISEASE C1 [Goel, Danny P.; Romanowski, James; Warner, Jon J. P.] Massachusetts Gen Hosp, Dept Orthoped Surg, Harvard Shoulder Serv, Yawkey Ctr Outpatient Serv, Boston, MA 02114 USA. [Namdari, Surena; Glaser, David] Hosp Univ Penn, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Harvard Shoulder Serv, Yawkey Ctr Outpatient Serv, Ste 3G,55 Fruit St, Boston, MA 02114 USA. EM jwarner@partners.org FU Zimmer FX Jon J.P. Warner receives royalties and institutional and research support from Zimmer. The remaining authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article. NR 55 TC 4 Z9 5 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP PY 2011 VL 20 IS 6 BP 1016 EP 1024 DI 10.1016/j.jse.2011.03.016 PG 9 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 818QZ UT WOS:000294771000029 PM 21705237 ER PT J AU Duckworth, AD Clement, ND Aitken, SA Ring, D McQueen, MM AF Duckworth, Andrew D. Clement, Nicholas D. Aitken, Stuart A. Ring, David McQueen, Margaret M. TI Essex-Lopresti lesion associated with an impacted radial neck fracture: interest of ulnar shortening in the secondary management of sequelae SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID DISTAL RADIOULNAR JOINT; INTEROSSEOUS MEMBRANE; CADAVER FOREARM; DISLOCATION; HEAD; INJURY; DISSOCIATION; REPLACEMENT C1 [Duckworth, Andrew D.; Clement, Nicholas D.; Aitken, Stuart A.; McQueen, Margaret M.] Royal Infirm Edinburgh NHS Trust, Edinburgh Orthopaed Trauma Unit, Edinburgh EH16 4SU, Midlothian, Scotland. [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Duckworth, AD (reprint author), Royal Infirm Edinburgh NHS Trust, Edinburgh Orthopaed Trauma Unit, 51 Little France Crescent, Edinburgh EH16 4SU, Midlothian, Scotland. EM andrew.duckworth@yahoo.co.uk FU Joint Active Systems; Biomet; Stryker; Orthopaedic Trauma Association; Wright Medical; Tornier; Acumed; Skeletal Dynamics; Illuminos; Mimedex; AO North America FX Dr Ring has the following disclosures, none of which related to this article: He has study-specific grants with Joint Active Systems, Biomet, Stryker, and the Orthopaedic Trauma Association. He is a consultant for Wright Medical, Tornier, Acumed, Skeletal Dynamics, Joint Active Systems, and Biomet. He has honoraria with AO North America and AO International. Royalties have been received from Wright Medical, and he has stock options with Illuminos and Mimedex. He has funding for a hand surgery fellowship through AO North America. He is Deputy Editor, Review Articles, Journal of Hand Surgery (American); Deputy Editor, Hand and Wrist, Journal of Orthopaedic Trauma; and is an Assistant Editor, Journal of Shoulder and Elbow Surgery. NR 27 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP PY 2011 VL 20 IS 6 BP E19 EP E24 DI 10.1016/j.jse.2011.02.017 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 818QZ UT WOS:000294771000005 PM 21602063 ER PT J AU Pennington, SD Dias, CM Warner, JJP AF Pennington, Scott D. Dias, Carlos M. Warner, Jon J. P. TI Shoulder arthroplasty in patients with dwarfism: a report of 2 cases SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID TOTAL HIP-ARTHROPLASTY; TOTAL KNEE ARTHROPLASTY; DIASTROPHIC DYSPLASIA; SKELETAL DYSPLASIA; OSTEOARTHRITIS C1 [Pennington, Scott D.; Dias, Carlos M.; Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Yawkey Outpatient Bldg,Suite 3G,55 Fruit St, Boston, MA 02114 USA. EM jwarner@partners.org NR 23 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP PY 2011 VL 20 IS 6 BP E1 EP E6 DI 10.1016/j.jse.2011.02.019 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 818QZ UT WOS:000294771000001 PM 21602066 ER PT J AU Forcade, NA Parchman, ML Jorgensen, JH Du, LC Nyren, NR Trevino, LB Pena, J Mann, MW Munoz, A Trevino, SB Mortensen, EM Wickes, BL Pollock, BH Frei, CR AF Forcade, Nicolas A. Parchman, Michael L. Jorgensen, James H. Du, Liem C. Nyren, Natalie R. Trevino, Lucina B. Pena, Joel Mann, Michael W. Munoz, Abilio Trevino, Sylvia B. Mortensen, Eric M. Wickes, Brian L. Pollock, Brad H. Frei, Christopher R. TI Prevalence, Severity, and Treatment of Community-Acquired Methicillin-Resistant Staphylococcus Aureus (CA-MRSA) Skin and Soft Tissue Infections in 10 Medical Clinics in Texas: A South Texas Ambulatory Research Network (STARNet) Study SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Antibiotics; CA-MRSA; Epidemiology; Practice-based Research; Soft Tissue Infections ID EMERGENCY-DEPARTMENT; TRIMETHOPRIM-SULFAMETHOXAZOLE; CLINDAMYCIN; ABSCESSES; EPIDEMIOLOGY; MANAGEMENT; CEPHALEXIN; DIAGNOSIS; THERAPY; VISITS AB Objectives: Quantify the prevalence, measure the severity, and describe treatment patterns in patients who present to medical clinics in Texas with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft-tissue infections (SSTI). Methods: Ten primary care clinics participated in this prospective, community-based study. Clinicians consented patients and collected clinical information, pictures, and wound swabs; data were processed centrally. MRSASelect (TM) was used for identification. Susceptibilities were determined via Etest (R) Results: Overall, 73 of 119 (61%) patients presenting with SSTIs meeting eligibility requirements had CA-MRSA. Among these, 49% were male, 79% were Hispanic, and 30% had diabetes. Half (56%) of the lesions were >= 5 cm in diameter. Most patients had abscesses (82%) and many reported pain scores of >= 7 of 10 (67%). Many presented with erythema (85%) or drainage (56%). Most received incision and drainage plus an antibiotic (64%). Antibiotic monotherapy was frequently prescribed: trimethoprim-sulfamethoxazole (TMP-SMX) (78%), clindamycin (4%), doxycycline (2%), and mupirocin (2%). The rest received TMP-SMX in combination with other antibiotics. TMP-SMX was frequently administered as one double-strength tablet twice daily. Isolates were 93% susceptible to clindamycin and 100% susceptible to TMP-SMX, doxycycline, vancomycin, and linezolid. Conclusions: We report a predominance of CA-MRSA SSTIs, favorable antibiotic susceptibilities, and frequent use of TMP-SMX in primary care clinics. (J Am Board Fam Med 2011;24:543-550.) C1 [Forcade, Nicolas A.; Frei, Christopher R.] Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. [Forcade, Nicolas A.; Parchman, Michael L.; Jorgensen, James H.; Mortensen, Eric M.; Wickes, Brian L.; Pollock, Brad H.; Frei, Christopher R.] Univ Texas San Antonio, Hlth Sci Ctr, Sch Med, San Antonio, TX USA. [Parchman, Michael L.; Mortensen, Eric M.] S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Program, San Antonio, TX USA. [Du, Liem C.; Nyren, Natalie R.; Trevino, Lucina B.; Pena, Joel; Mann, Michael W.; Munoz, Abilio; Trevino, Sylvia B.] S Texas Ambulatory Res Network STARNet, San Antonio, TX USA. RP Frei, CR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Pharmacotherapy Educ & Res Ctr PERC, 7703 Floyd Curl Dr,MSC 6220, San Antonio, TX 78229 USA. EM freic@uthscsa.edu OI Mortensen, Eric/0000-0002-3880-5563 FU United States National Institutes of Health [UL1 RR025767, KL2 RR025766]; South Texas Veterans Health Care System FX Funding: This work was supported by the United States National Institutes of Health in the form of a CTSA pilot project grant (UL1 RR025767) and a KL2 career development award (KL2 RR025766), both awarded to Dr. Frei. Drs. Parchman and Mortensen were supported by the South Texas Veterans Health Care System when this work was completed. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 30 TC 26 Z9 29 U1 2 U2 8 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD SEP-OCT PY 2011 VL 24 IS 5 BP 543 EP 550 DI 10.3122/jabfm.2011.05.110073 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 817IC UT WOS:000294664300012 PM 21900437 ER PT J AU Hayes, H Parchman, ML Howard, R AF Hayes, Holly Parchman, Michael L. Howard, Ray TI A Logic Model Framework for Evaluation and Planning in a Primary Care Practice-based Research Network (PBRN) SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Evaluation; Logic Model; Practice-based Research ID TIME PHYSICAL-ACTIVITY; RISK-FACTORS; SOUTH TEXAS; BARRIERS; STARNET; BEHAVIORS; SETTINGS; BENEFITS; GLUCOSE; CLINICS AB Evaluating effective growth and development of a practice-based research network (PBRN) can be challenging. The purpose of this article is to describe the development of a logic model and how the framework has been used for planning and evaluation in a primary care PBRN. An evaluation team was formed consisting of the PBRN directors, staff, and its board members. After the mission and the target audience were determined, facilitated meetings and discussions were held with stakeholders to identify the assumptions, inputs, activities, outputs, outcomes, and outcome indicators. The long-term outcomes outlined in the final logic model are 2-fold: (1) improved health outcomes of patients served by PBRN community clinicians and (2) community clinicians are recognized leaders of quality research projects. The logic model proved useful in identifying stakeholder interests and dissemination activities as an area that required more attention in the PBRN. The logic model approach is a useful planning tool and project management resource that increases the probability that the PBRN mission will be successfully implemented. (J Am Board Fam Med 2011;24:576-582.) C1 [Hayes, Holly; Parchman, Michael L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Parchman, Michael L.] S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Program, San Antonio, TX USA. [Howard, Ray] Acad Ctr Excellence Teaching, San Antonio, TX USA. RP Hayes, H (reprint author), 7703 Floyd Curl Dr,Mail Code 7728, San Antonio, TX 78229 USA. EM hayesh@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU NCRR/NIH [UL1RR025767]; South Texas Ambulatory Research Network FX Funding: Funding for this study was provided by Clinical Translational Science Award No. UL1RR025767 from NCRR/NIH to the University of Texas Health Sciences Center at San Antonio.; The authors would like to thank the members of the South Texas Ambulatory Research Network for their support and contribution to this study. NR 37 TC 15 Z9 15 U1 0 U2 5 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD SEP-OCT PY 2011 VL 24 IS 5 BP 576 EP 582 DI 10.3122/jabfm.2011.05.110043 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 817IC UT WOS:000294664300016 PM 21900441 ER PT J AU Abi-Haidar, Y Sanchez, V Itani, KMF AF Abi-Haidar, Youmna Sanchez, Vivian Itani, Kamal M. F. TI Risk Factors and Outcomes of Acute Versus Elective Groin Hernia Surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; INGUINAL-HERNIA; REPAIR; STRANGULATION AB BACKGROUND: Hernia characteristics and patient factors associated with acute compared with elective groin hernia surgery are unknown. STUDY DESIGN: A retrospective study of 1,034 consecutive groin hernia repair cases performed between 2001 and 2009 at a single Veterans Affairs Hospital was conducted. Patient variables, hernia characteristics, time to surgery, and morbidity and mortality outcomes were abstracted and compared between acute and elective hernia repairs. A Kaplan-Meier survival analysis for the two groups was also performed. Logistic regression analysis was conducted to identify associations between type of surgery, patient demographics, and hernia characteristics. RESULTS: Compared with 971 elective repair patients, the 63 acute repair patients had a higher rate of femoral hernias (2.5% vs 7.4%, p = 0.03), a higher rate of scrotal hernias (16.2% vs 32.4%, p = 0.0006), and a higher rate of recurrent hernias (16.7% vs 30.9%, p = 0.0026). Patient age, femoral, scrotal, and recurrent hernias were significantly associated with acute hernia presentation on univariate and multivariable analyses. Complications occurred in 27% and 15.1% of acute and elective repair patients, respectively (p = 0.01). Intraoperative organ resection was required in 7 (11.1%) acute hernia repairs, and in 2 (0.2%) elective repairs (p = 0.0001). Three acute repair patients (4.8%) underwent reoperation within 30 days after surgery, compared with 15 elective repair patients (1.5%), p = 0.05. Age-adjusted Kaplan-Meier survival analysis revealed a shorter time to death among acute repair patients compared with elective repair patients (p = 0.0001). CONCLUSIONS: Age, femoral, scrotal, and recurrent groin hernias are associated with increased risk for acute hernia surgery. Acute hernia repair carries a higher morbidity and lower survival. (J Am Coll Surg 2011;213:363-369. (C) 2011 by the American College of Surgeons) C1 [Abi-Haidar, Youmna; Sanchez, Vivian; Itani, Kamal M. F.] VA Boston Healthcare Syst, Boston, MA USA. [Abi-Haidar, Youmna; Sanchez, Vivian; Itani, Kamal M. F.] Boston Univ, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. RP Itani, KMF (reprint author), VABHCS 112A,1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM kitani@va.gov OI Sanchez, Vivian/0000-0001-5565-9687 NR 24 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2011 VL 213 IS 3 BP 363 EP 369 DI 10.1016/j.jamcollsurg.2011.05.008 PG 7 WC Surgery SC Surgery GA 817KF UT WOS:000294670600005 PM 21680204 ER PT J AU Bartlett, E Yoon, SS AF Bartlett, Edmund Yoon, Sam S. TI Current Treatment for the Local Control of Retroperitoneal Sarcomas SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Review ID SOFT-TISSUE SARCOMA; BEAM RADIATION-THERAPY; POPULATION-BASED-ANALYSIS; INFERIOR VENA-CAVA; POSTOPERATIVE NOMOGRAM; ADJUVANT CHEMOTHERAPY; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; DOSE-ESCALATION; RADIOTHERAPY C1 [Yoon, Sam S.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Yoon, Sam S.] Harvard Univ, Sch Med, Boston, MA USA. [Bartlett, Edmund] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Yoon, Sam S.] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 7B,55 Fruit St, Boston, MA 02114 USA. EM syoon@partners.org OI Bartlett, Edmund/0000-0002-0923-153X NR 72 TC 5 Z9 5 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 SEP PY 2011 VL 213 IS 3 BP 436 EP 446 DI 10.1016/j.jamcollsurg.2011.05.025 PG 11 WC Surgery SC Surgery GA 817KF UT WOS:000294670600014 PM 21723153 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Have We Been Down This Road Before? SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2011 VL 9 IS 9 BP 953 EP 953 PG 1 WC Oncology SC Oncology GA 816FU UT WOS:000294584900001 PM 21917620 ER PT J AU Motzer, RJ Agarwal, N Beard, C Bhayani, S Bolger, GB Carducci, MA Chang, SS Choueiri, TK Hancock, SL Hudes, GR Jonasch, E Josephson, D Kuzel, TM Levine, EG Lin, DW Margolin, KA Michaelson, MD Olencki, T Pill, R Ratliff, TW Redman, BG Robertson, CN Ryan, CJ Sheinfeld, J Spiess, PE Wang, J Wilder, RB AF Motzer, Robert J. Agarwal, Neeraj Beard, Clair Bhayani, Sam Bolger, Graeme B. Carducci, Michael A. Chang, Sam S. Choueiri, Toni K. Hancock, Steven L. Hudes, Gary R. Jonasch, Eric Josephson, David Kuzel, Timothy M. Levine, Ellis G. Lin, Daniel W. Margolin, Kim A. Michaelson, M. Dror Olencki, Thomas Pill, Roberto Ratliff, Thomas W. Redman, Bruce G. Robertson, Cary N. Ryan, Charles J. Sheinfeld, Joel Spiess, Philippe E. Wang, Jue Wilder, Richard B. CA NCCN Kidney Canc Panel TI NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; renal cell carcinoma; clear cell tumors; kidney disease; nephrectomy ID RENAL-CELL CARCINOMA; REFRACTORY SOLID TUMORS; PHASE-III TRIAL; NEPHRON-SPARING SURGERY; GROWTH-FACTOR RECEPTOR; DOSE RECOMBINANT INTERLEUKIN-2; KINASE INHIBITORS SORAFENIB; NORMAL CONTRALATERAL KIDNEY; DAYS ON/7 DAYS; RADICAL NEPHRECTOMY C1 [Motzer, Robert J.; Sheinfeld, Joel] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Bhayani, Sam] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Bhayani, Sam] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Bolger, Graeme B.] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Jonasch, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Kuzel, Timothy M.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Levine, Ellis G.; Pill, Roberto] Roswell Pk Canc Inst, Buffalo, NY USA. [Lin, Daniel W.] Univ Washington, Seattle, WA 98195 USA. [Margolin, Kim A.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Michaelson, M. Dror] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Olencki, Thomas] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Ratliff, Thomas W.] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Redman, Bruce G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Ryan, Charles J.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Spiess, Philippe E.; Wilder, Richard B.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. RP Motzer, RJ (reprint author), Mem Sloan Kettering Canc Ctr, New York, NY USA. NR 87 TC 40 Z9 41 U1 1 U2 6 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2011 VL 9 IS 9 BP 960 EP 977 PG 18 WC Oncology SC Oncology GA 816FU UT WOS:000294584900003 PM 21917622 ER PT J AU Hoppe, RT Advani, RH Ai, WYZ Ambinder, RF Bello, CM Bierman, PJ Blum, KA Dabaja, B Duron, Y Forero, A Gordon, LI Hernandez-Ilizaliturri, FJ Hochberg, EP Maloney, DG Mansur, D Mauch, PM Metzger, M Moore, JO Morgan, D Moskowitz, CH Poppe, M Pro, B Weiss, L Winter, JN Yahalom, J AF Hoppe, Richard T. Advani, Ranjana H. Ai, Weiyun Z. Ambinder, Richard F. Bello, Celeste M. Bierman, Philip J. Blum, Kristie A. Dabaja, Bouthaina Duron, Ysabel Forero, Andres Gordon, Leo I. Hernandez-Ilizaliturri, Francisco J. Hochberg, Ephraim P. Maloney, David G. Mansur, David Mauch, Peter M. Metzger, Monika Moore, Joseph O. Morgan, David Moskowitz, Craig H. Poppe, Matthew Pro, Barbara Weiss, Lawrence Winter, Jane N. Yahalom, Joachim CA NCCN Clinical Practice Guidelines TI NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE Clinical Practice Guidelines; NCCN Guidelines; Hodgkin disease; lymphoma; classical Hodgkin disease; lymphocyte predominance; combined modality therapy ID STEM-CELL TRANSPLANTATION; INVOLVED-FIELD RADIOTHERAPY; POSITRON-EMISSION-TOMOGRAPHY; HIGH-DOSE THERAPY; FINE-NEEDLE-ASPIRATION; STUDY-GROUP GHSG; BONE-MARROW-TRANSPLANTATION; COMBINED-MODALITY TREATMENT; NEGATIVE PREDICTIVE-VALUE; RADIATION-THERAPY C1 [Hoppe, Richard T.; Advani, Ranjana H.] Stanford Canc Inst, Stanford, CA USA. [Ai, Weiyun Z.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Ambinder, Richard F.] Sidney Kimmel Comprehens Canc Ctr John Hopkins, Sidney, BC, Canada. [Bierman, Philip J.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Blum, Kristie A.] Ohio State Univ, Richard J Solove Res Inst, Columbus, OH 43210 USA. [Dabaja, Bouthaina] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Forero, Andres] Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Gordon, Leo I.; Winter, Jane N.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Hernandez-Ilizaliturri, Francisco J.] Roswell Pk Canc Inst, Buffalo, NY USA. [Hochberg, Ephraim P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Maloney, David G.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Mansur, David] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Mansur, David] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Metzger, Monika] Univ Tennessee, Inst Canc, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Moore, Joseph O.] Duke Canc Inst, Durham, NC USA. [Morgan, David] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Moskowitz, Craig H.; Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Poppe, Matthew] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Pro, Barbara] Fox Chase Canc Ctr, Philadelphia, PA USA. [Weiss, Lawrence] City Hope Comprehens Canc Ctr, Duarte, CA USA. RP Hoppe, RT (reprint author), Stanford Canc Inst, Stanford, CA USA. RI Blum, Kristie/E-2768-2011 NR 138 TC 28 Z9 29 U1 0 U2 2 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2011 VL 9 IS 9 BP 1020 EP 1058 PG 39 WC Oncology SC Oncology GA 816FU UT WOS:000294584900007 PM 21917626 ER PT J AU Jensen, MO Jensen, H Levine, RA Yoganathan, AP Andersen, NT Nygaard, H Hasenkam, JM Nielsen, SL AF Jensen, Morten O. Jensen, Henrik Levine, Robert A. Yoganathan, Ajit P. Andersen, Niels Trolle Nygaard, Hans Hasenkam, J. Michael Nielsen, Sten L. TI Saddle-shaped mitral valve annuloplasty rings improve leaflet coaptation geometry SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID CHORDAL FORCE DISTRIBUTION; ANTERIOR LEAFLET; IN-VIVO; REGURGITATION; CURVATURE; DYNAMICS; RECONSTRUCTION; MECHANISM; TENDINEAE; INSIGHTS AB Objectives: The mitral valve annulus naturally conforms to a saddle shape in systole. This configuration is believed to put the leaflets into a lower-energy equilibrium with the annulus and subvalvular apparatus. Conventional flat annuloplasty rings restrict posterior leaflet motion, which may result in a "monocusp" valve, affecting valvular stress distribution. It is hypothesized that saddle-shaped annuloplasty rings cause less distortion of the physiologic leaflet geometry than do flat rings. Methods: Twelve pigs were studied in an acute setting with 3-dimensional echocardiography and sonomicrometry before and after implantation of rigid flat (n = 5) and saddle-shaped (n = 7) annuloplasty rings. The rings were true sized to the annulus with equal anterior-posterior and commissure-commissure circumferential dimensions. The saddle-shaped rings had an annular height to commissural width ratio of 15%. Results: Saddle-shaped rings maintained both leaflets operational (P < .01). Flat rings made the posterior leaflet immobile and the anterior leaflet aligned flat along the annulus in systole, effectively resulting in monoleaflet function. The average distance from the papillary muscle tips to the posterior annulus decreased by 2.4 +/- 0.4 mm after flat ring implantation (P < .01). Conclusions: Saddle-shaped annuloplasty rings provide better leaflet coaptation geometry than do flat rings by not hoisting the papillary muscles toward the posterior annulus through the commissural chordae, allowing greater leaflet mobility. This entails a potentially beneficial impact on valvular stress distribution that could affect durability of the repaired valve. (J Thorac Cardiovasc Surg 2011;142:697-703) C1 [Jensen, Morten O.; Jensen, Henrik; Nygaard, Hans; Hasenkam, J. Michael; Nielsen, Sten L.] Aarhus Univ Hosp, Dept Cardiothorac & Vasc Surg, Inst Clin Med, DK-8200 Aarhus N, Denmark. [Jensen, Morten O.; Nygaard, Hans] Engn Coll Aarhus, Dept Biomed Engn, Aarhus, Denmark. [Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Yoganathan, Ajit P.] Georgia Inst Technol, Wallace H Coulter Sch Biomed Engn, Atlanta, GA 30332 USA. [Yoganathan, Ajit P.] Emory Univ, Atlanta, GA 30322 USA. [Andersen, Niels Trolle] Aarhus Univ, Dept Biostat, Aarhus, Denmark. RP Jensen, MO (reprint author), Aarhus Univ Hosp, Dept Cardiothorac & Vasc Surg, Inst Clin Med, DK-8200 Aarhus N, Denmark. EM dr.morten.jensen@gmail.com FU Danish Heart Foundation [B248-A389-30, B248-A946-38, 07-4-B248-A1380-22362]; A.P. Moller Foundation for the Advancement of Medical Science; Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond; Horslev Fonden; Aase og Ejnar Danielsens Fond; The Danish Medical Association Research Fund; Helga og Peter Kornings Fund; Simon Fougner Hartmanns Famile Fond; Jens Anker Andersen Fonden; Kobmand Sven Hansen og hustru Ina Hansens Fond; Lykfeldts Legat; Kong Christian den Tiendes Fond; Eva & Henry Fraenkels Mindefond; Dr Poul M. Christiansens hustrus fond; Frimodt-Heineke Fonden; Kirsten Anthonius' Mindelegat; National Heart, Lung, and Blood Institute (NHLBI) [HL 52009, K24 HL67434]; Leducq Foundation, Paris, France [07CVD04] FX This research project was funded by the Danish Heart Foundation grants #B248-A389-30, #B248-A946-38, and #07-4-B248-A1380-22362, the A.P. Moller Foundation for the Advancement of Medical Science, Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond, Horslev Fonden, Aase og Ejnar Danielsens Fond, The Danish Medical Association Research Fund, Helga og Peter Kornings Fund, Simon Fougner Hartmanns Famile Fond, Jens Anker Andersen Fonden, Kobmand Sven Hansen og hustru Ina Hansens Fond, Lykfeldts Legat, Kong Christian den Tiendes Fond, Eva & Henry Fraenkels Mindefond, Dr Poul M. Christiansens & hustrus fond, Frimodt-Heineke Fonden, and Kirsten Anthonius' Mindelegat. Dr Ajit P. Yoganathan's participation in this research project was funded by the National Heart, Lung, and Blood Institute (NHLBI) grant #HL 52009. Dr Robert A. Levine's participation was supported by NHLBI grant #K24 HL67434 as well as grant 07CVD04 from the Leducq Foundation, Paris, France, for the Leducq MITRAL Transatlantic Network. NR 32 TC 33 Z9 33 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD SEP PY 2011 VL 142 IS 3 BP 697 EP 703 DI 10.1016/j.jtcvs.2011.01.022 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 807FQ UT WOS:000293882100048 PM 21329946 ER PT J AU Sundt, TM AF Sundt, Thoralf M., III TI The can-should problem SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St, Boston, MA 02114 USA. EM tsundt@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD SEP PY 2011 VL 142 IS 3 BP E91 EP E91 DI 10.1016/j.jtcvs.2011.04.002 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 807FQ UT WOS:000293882100004 PM 21843758 ER PT J AU Trimarchi, S Jonker, FHW Hutchison, S Isselbacher, EM Pape, LA Patel, HJ Froehlich, JB Muhs, BE Rampoldi, V Grassi, V Evangelista, A Meinhardt, G Beckman, J Myrmel, T Pyeritz, RE Hirsch, AT Sundt, TM Nienaber, CA Eagle, KA AF Trimarchi, Santi Jonker, Frederik H. W. Hutchison, Stuart Isselbacher, Eric M. Pape, Linda A. Patel, Himanshu J. Froehlich, James B. Muhs, Bart E. Rampoldi, Vincenzo Grassi, Viviana Evangelista, Arturo Meinhardt, Gabriel Beckman, Joshua Myrmel, Truls Pyeritz, Reed E. Hirsch, Alan T. Sundt, Thoralf M., III Nienaber, Christoph A. Eagle, Kim A. TI Descending aortic diameter of 5.5 cm or greater is not an accurate predictor of acute type B aortic dissection SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MARFAN-SYNDROME; NATURAL-HISTORY; ANEURYSMS; COMPLICATIONS; PATTERNS; SURGERY; RUPTURE; DISEASE; GROWTH; RATES AB Objective: The risk of acute type B aortic dissection is thought to increase with descending thoracic aortic diameter. Currently, elective repair of the descending thoracic aorta is indicated for an aortic diameter of 5.5 cm or greater. We sought to investigate the relationship between aortic diameter and acute type B aortic dissection, and the utility of aortic diameter as a predictor of acute type B aortic dissection. Methods: We examined the descending aortic diameter at presentation of 613 patients with acute type B aortic dissection who were enrolled in the International Registry of Acute Aortic Dissection between 1996 and 2009, and analyzed the subset of patients with acute type B aortic dissection with an aortic diameter less than 5.5 cm. Results: The median aortic diameter at the level of acute type B aortic dissection was 4.1 cm (range 2.1-13.0 cm). Only 18.4% of patients with acute type B aortic dissection in the International Registry of Acute Aortic Dissection had an aortic diameter of 5.5 cm or greater. Patients with Marfan syndrome represented 4.3% and had a slightly larger aortic diameter than patients without Marfan syndrome (4.68 vs 4.32 cm, P=.121). Complicated acute type B aortic dissection was more common among patients with an aortic diameter of 5.5 cm or greater (52.2% vs 35.6%, P<.001), and the in-hospital mortality for patients with an aortic diameter less than 5.5 cm and 5.5 cm or greater was 6.6% and 23.0% (P<.001), respectively. Conclusions: The majority of patients with acute type B aortic dissection present with a descending aortic diameter less than 5.5 cm before dissection and are not within the guidelines for elective descending thoracic aortic repair. Aortic diameter measurements do not seem to be a useful parameter to prevent aortic dissection, and other methods are needed to identify patients at risk for acute type B aortic dissection. (J Thorac Cardiovasc Surg 2011;142:e101-7) C1 [Trimarchi, Santi; Rampoldi, Vincenzo; Grassi, Viviana] Univ Milan, Policlin San Donato IRCCS, Cardiovasc Ctr E Malan, Milan, Italy. [Jonker, Frederik H. W.; Muhs, Bart E.] Yale Univ, Sch Med, New Haven, CT USA. [Hutchison, Stuart] Univ Calgary, Calgary, AB, Canada. [Isselbacher, Eric M.] Massachusetts Gen Hosp, Boston, MA USA. [Pape, Linda A.] Univ Massachusetts Hosp, Worcester, MA USA. [Patel, Himanshu J.; Froehlich, James B.; Eagle, Kim A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Evangelista, Arturo] Hosp Gen Univ Vall dHebron, Barcelona, Spain. [Meinhardt, Gabriel] Robert Bosch Krankenhaus, Stuttgart, Germany. [Beckman, Joshua] Brigham & Womens Hosp, Boston, MA 02115 USA. [Myrmel, Truls] Univ Tromso Hosp, N-9012 Tromso, Norway. [Pyeritz, Reed E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Hirsch, Alan T.] Minneapolis Heart Inst, Minneapolis, MN USA. [Sundt, Thoralf M., III] Mayo Clin, Rochester, MN USA. [Nienaber, Christoph A.] Univ Rostock, Rostock, Germany. RP Trimarchi, S (reprint author), Univ Milan, Policlin S Donato IRCCS, Cardiovasc Ctr E Malan, Via Morandi 30, I-20097 San Donato Milanese, Italy. EM santi.trimarchi@unimi.it RI Trimarchi, Santi/J-7361-2016; OI Trimarchi, Santi/0000-0001-5996-3264; Beckman, Joshua/0000-0001-8332-8439 FU University of Michigan Health System; Varbedian Fund for Aortic Research; Mardigian Foundation; Gore Medical Inc (Flagstaff, Ariz) FX The IRAD is supported by grants from the University of Michigan Health System, the Varbedian Fund for Aortic Research, the Mardigian Foundation, and Gore Medical Inc (Flagstaff, Ariz). NR 24 TC 21 Z9 21 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD SEP PY 2011 VL 142 IS 3 BP E101 EP E107 DI 10.1016/j.jtcvs.2010.12.032 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 807FQ UT WOS:000293882100006 PM 21592525 ER PT J AU Shyn, PB Tatli, S Sainani, NI Morrison, PR Habbab, F Catalano, P Silverman, SG AF Shyn, Paul B. Tatli, Servet Sainani, Nisha I. Morrison, Paul R. Habbab, Fadi Catalano, Paul Silverman, Stuart G. TI Minimizing Image Misregistration during PET/CT-guided Percutaneous Interventions with Monitored Breath-hold PET and CT Acquisitions SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID LIVER METASTASES; REGISTRATION; RADIOFREQUENCY; ABLATION; CANCER; BIOPSY; THORAX; LUNG AB Purpose: To validate a monitored, breath-hold positron emission tomography (PET)/computed tomography (CT) acquisition technique for the minimization of respiratory PET/CT image misregistration and lesion distortion during PET/CT-guided percutaneous interventional procedures. Materials and Methods: Eleven patients referred for percutaneous biopsy or thermal ablation of tumors near the diaphragm were prospectively enrolled. Initial PET/CT scanning was performed by using a bellows device and monitored, same-level breath-holds for PET and CT acquisitions. Breath-hold PET consisted of nine 20-second breath-hold frames, yielding a 3-minute equivalent PET dataset. A second PET/CT scan was obtained without monitoring by using end-expiration breath-hold CT and free-breathing PET. PET/CT tumor misregistration and craniocaudal tumor diameter were measured on monitored and unmonitored PET/CT datasets. Data were analyzed by using nonparametric, two-sided, signed-rank statistical tests. Results: Mean PET/CT image misregistrations in the craniocaudal, anteroposterior, and transverse planes were 2.6 mm (range, 0-7 mm), 3.3 mm (range, 1-8 mm), and 2.7 mm (range, 0-8 mm) with monitoring and 14.7 mm (range, 0-49 mm), 7.6 mm (range, 1-24 mm), and 4.0 mm (range, 0-12 mm) without monitoring, respectively. Differences were significant for craniocaudal (P = .0087) and anteroposterior (P = .014) planes, but not for the transverse plane (P = .23). Mean craniocaudal target diameter was 2.5 mm (range, -2 to 9 mm) larger (ie, distorted) for unmonitored versus monitored PET (P = .061). Conclusions: Acquiring PET/CT datasets with respiratory bellows-assisted, monitored breath-holds improves PET/CT image registration versus unmonitored PET/CT and may facilitate accurate targeting during PET/CT guided interventions in anatomic regions subject to respiratory motion. C1 [Shyn, Paul B.; Tatli, Servet; Sainani, Nisha I.; Morrison, Paul R.; Habbab, Fadi; Silverman, Stuart G.] Brigham & Womens Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Catalano, Paul] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Shyn, PB (reprint author), Brigham & Womens Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 75 Francis St, Boston, MA 02115 USA. EM pshyn@partners.org FU Society of Interventional Radiology FX This study was funded by Society of Interventional Radiology Academic Transition Grant. None of the authors have identified a conflict of interest. NR 20 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2011 VL 22 IS 9 BP 1287 EP 1292 DI 10.1016/j.jvir.2011.06.015 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 816IT UT WOS:000294592600011 PM 21778067 ER PT J AU Eckler, K AF Eckler, Kristen TI More treatment options for overactive bladder in postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID LOWER URINARY-TRACT; SYMPTOMS; THERAPY; IMPACT C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Eckler, K (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SEP PY 2011 VL 18 IS 9 BP 941 EP 942 DI 10.1097/gme.0b013e31822b29f9 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 812HA UT WOS:000294280500004 PM 21869637 ER PT J AU Demicco, EG Farris, AB Baba, Y Agbor-Etang, B Bergethon, K Mandal, R Daives, D Fukuoka, J Shimizu, M Dias-Santagata, D Ogino, S Iafrate, AJ Gaissert, HA Mino-Kenudson, M AF Demicco, Elizabeth G. Farris, Alton B., III Baba, Yoshifumi Agbor-Etang, Brian Bergethon, Kristin Mandal, Rajni Daives, Diane Fukuoka, Junya Shimizu, Michio Dias-Santagata, Dora Ogino, Shuji Iafrate, A. John Gaissert, Henning A. Mino-Kenudson, Mari TI The dichotomy in carcinogenesis of the distal esophagus and esophagogastric junction: intestinal-type vs cardiac-type mucosa-associated adenocarcinoma SO MODERN PATHOLOGY LA English DT Article DE adenocarcinoma; Barrett esophagus; carcinogenesis; distal esophagus; esophagogastric junction; prognosis ID GROWTH-FACTOR RECEPTOR; CDX2 MUTANT MICE; BARRETTS-ESOPHAGUS; GASTROESOPHAGEAL JUNCTION; GASTRIC CARDIA; BETA-CATENIN; NUCLEAR ACCUMULATION; PROGNOSTIC FACTORS; MUC6 EXPRESSION; HOMEOBOX GENE AB Adenocarcinoma of the distal esophagus and esophagogastric junction continues to rise in incidence. An intestinal metaplasia (Barrett esophagus)-dysplasia-carcinoma sequence induced by gastroesophageal reflux disease is well established. However, a significant number of adenocarcinomas in the vicinity of the esophagogastric junction are seen in the background of gastric/cardiac-type mucosa without intestinal metaplasia. Thus, the aim of this study was to investigate the role of Barrett esophagus (intestinal-type mucosa) in the classification and prognosis of tumors of the distal esophagus and esophagogastric junction. Clinicopathological and molecular characteristics were examined in 157 consecutively resected adenocarcinomas of the distal esophagus and esophagogastric junction and were compared between tumors arising in association with intestinal-type and cardiac-type mucosa. Intestinal-type mucosa-associated adenocarcinomas were more likely to be associated with younger age (P=0.0057), reflux symptoms (P<0.0001), proximal location (P=0.0009), lower T stage (P<0.0001), fewer nodal metastases (P=0.0001), absence of lymphatic (P<0.0001), venous (P=0.0060) or perineural (P<0.0001) invasion. Histologically, intestinal-type mucosa-associated tumors were more likely to be low-grade glandular tumors (P-0.0095) of intestinal or mixed immunophenotype (P-0.015) and express nuclear beta-catenin (P-0.0080), whereas tumors arising in a background of cardiac-type mucosa were more frequently associated with EGFR amplification (P=0.0051). Five-year overall survival rate was significantly higher in patients with intestinal-type mucosa-associated tumors (28 vs 9%, P=0.0015), although no survival benefit was seen after adjusting for potential confounders. Our findings support the theory that multiple distinct pathways of tumorigenesis exist in the vicinity of the esophagogastric junction, including one in which tumors arise from dysplastic intestinal metaplasia (intestinal pathway), and one potentially involving dysplasia of the cardiac-type mucosa (non-intestinal pathway). Additional studies are warranted to further clarify their pathogenesis and the molecular mechanisms involved. Modern Pathology (2011) 24, 1177-1190; doi:10.1038/modpathol. 2011.77; published online 13 May 2011 C1 [Demicco, Elizabeth G.; Farris, Alton B., III; Bergethon, Kristin; Mandal, Rajni; Dias-Santagata, Dora; Iafrate, A. John; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Demicco, Elizabeth G.; Farris, Alton B., III; Baba, Yoshifumi; Agbor-Etang, Brian; Bergethon, Kristin; Mandal, Rajni; Daives, Diane; Dias-Santagata, Dora; Ogino, Shuji; Iafrate, A. John; Gaissert, Henning A.; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Farris, Alton B., III] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. [Baba, Yoshifumi; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fukuoka, Junya] Toyama Med Univ, Dept Pathol, Toyama, Japan. [Shimizu, Michio] Saitama Med Univ, Dept Pathol, Int Med Ctr, Saitama, Japan. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA. EM mminokenudson@partners.org NR 68 TC 19 Z9 19 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2011 VL 24 IS 9 BP 1177 EP 1190 DI 10.1038/modpathol.2011.77 PG 14 WC Pathology SC Pathology GA 817MU UT WOS:000294678500003 PM 21572404 ER PT J AU Lund, P Kotova, I Kedinger, V Khanwalkar, H Voltz, E Hahn, WC Gronemeyer, H AF Lund, Per Kotova, Irina Kedinger, Valerie Khanwalkar, Harshal Voltz, Emilie Hahn, William C. Gronemeyer, Hinrich TI Transformation-Dependent Silencing of Tumor-Selective Apoptosis-Inducing TRAIL by DNA Hypermethylation Is Antagonized by Decitabine SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID DEATH LIGAND TRAIL; ACUTE MYELOID-LEUKEMIA; EPITHELIAL-CELLS; DEFICIENT MICE; CANCER; METHYLATION; EXPRESSION; RECEPTORS; GENE; ACTIVATION AB TNF-related apoptosis-inducing ligand (TRAIL) kills tumor cells selectively. We asked how emerging tumor cells escape elimination by TRAIL and how tumor-specific killing by TRAIL could then be restored. We found that TRAIL expression is consistently downregulated in HRAS(G12V)-transformed cells in stepwise tumorigenesis models derived from four different tissues due to DNA hypermethylation of CpG clusters within the TRAIL promoter. Decitabine de-silenced TRAIL, which remained inducible by interferon, while induction of TRAIL by blocking the HRAS(G12V)-activated mitogen-activated protein kinase pathway was subordinated to epigenetic silencing. Decitabine induced apoptosis through upregulation of endogenous TRAIL in cooperation with favorable regulation of key players acting in TRAIL-mediated apoptosis. Apoptosis induction by exogenously added TRAIL was largely increased by decitabine. In vivo treatment of xenografted human HRAS(G12V)-transformed human epithelial kidney or syngenic mice tumors by decitabine blocked tumor growth induced TRAIL expression and apoptosis. Our results emphasize the potential of decitabine to enhance TRAIL-induced apoptosis in tumors and thus provide a rationale for combination therapies with decitabine to increase tumor-selective apoptosis. Mol Cancer Ther; 10(9); 1611-23. (C)2011 AACR. C1 [Lund, Per; Kotova, Irina; Kedinger, Valerie; Khanwalkar, Harshal; Voltz, Emilie; Gronemeyer, Hinrich] Univ Strasbourg, INSERM, CNRS, Dept Canc Biol,IGBMC, F-67404 Illkirch Graffenstaden, France. [Hahn, William C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Gronemeyer, H (reprint author), Univ Strasbourg, INSERM, CNRS, Dept Canc Biol,IGBMC, 1 Rue Laurent Fries,BP 10142, F-67404 Illkirch Graffenstaden, France. EM hg@igbmc.fr RI Gronemeyer, Hinrich/G-6240-2011; Gronemeyer, Hinrich/H-7002-2016 OI Gronemeyer, Hinrich/0000-0001-9454-2449; Gronemeyer, Hinrich/0000-0001-9454-2449 FU Ligue National Contre le Cancer (laboratoire labelise); European Community [LSHC-CT-2005-518417, HEALTH-F4-2007-200767]; Institut National du Cancer; Association de Recherche Contre le Cancer; Ligue National Contre le Cancer FX This work was financially supported by the Ligue National Contre le Cancer (laboratoire labelise), and the European Community contracts LSHC-CT-2005-518417 "Epitron" and HEALTH-F4-2007-200767 "Apo-Sys". P. Lund was supported by the Institut National du Cancer, I. Kotova by the Association de Recherche Contre le Cancer, and V. Kedinger by the Ligue National Contre le Cancer. NR 48 TC 10 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD SEP PY 2011 VL 10 IS 9 BP 1611 EP 1623 DI 10.1158/1535-7163.MCT-11-0140 PG 13 WC Oncology SC Oncology GA 817JR UT WOS:000294668900009 PM 21697397 ER PT J AU Breakefield, XO Frederickson, RM Simpson, RJ AF Breakefield, Xandra O. Frederickson, Robert M. Simpson, Richard J. TI Gesicles: Microvesicle "Cookies" for Transient Information Transfer Between Cells SO MOLECULAR THERAPY LA English DT Editorial Material ID DIAGNOSTIC BIOMARKERS; EXOSOMES; CANCER; MECHANISM; DELIVERY; RNA C1 [Breakefield, Xandra O.] Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. [Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. [Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Frederickson, Robert M.] Robert M Frederickson Consulting Inc, Seattle, WA USA. [Simpson, Richard J.] La Trobe Univ, La Trobe Univ Inst Mol Sci LIMS, Bundoora, Vic, Australia. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu RI Simpson, Richard/A-6947-2012 NR 22 TC 14 Z9 15 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD SEP PY 2011 VL 19 IS 9 BP 1574 EP 1576 DI 10.1038/mt.2011.169 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 817LO UT WOS:000294674700002 PM 21886114 ER PT J AU Chmielowiec, J Chang, YS Chien, KR AF Chmielowiec, Jolanta Chang, Yuh-Shin Chien, Kenneth R. TI A GPS for Heart Progenitor Cell Lineages SO MOLECULAR THERAPY LA English DT Editorial Material ID CARDIOMYOCYTES; FIBROBLASTS; MUSCLE C1 [Chmielowiec, Jolanta; Chang, Yuh-Shin; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Chmielowiec, Jolanta; Chang, Yuh-Shin; Chien, Kenneth R.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 55 Fruit St, Boston, MA 02114 USA. EM krchien@partners.org FU NHLBI NIH HHS [U01 HL100408] NR 11 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD SEP PY 2011 VL 19 IS 9 BP 1576 EP 1578 DI 10.1038/mt.2011.158 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 817LO UT WOS:000294674700003 PM 21886115 ER PT J AU Coumans, JV Walcott, BP Butler, WE Nahed, BV Kahle, KT AF Coumans, Jean-Valery Walcott, Brian P. Butler, William E. Nahed, Brian V. Kahle, Kristopher T. TI Volumetric analysis of syringomyelia following hindbrain decompression for Chiari malformation Type I: syringomyelia resolution follows exponential kinetics SO NEUROSURGICAL FOCUS LA English DT Article DE Chiari malformation; syringomyelia; syrinx; MR imaging; volumetrics ID POSTERIOR-FOSSA; PATHOPHYSIOLOGY; MODEL AB Object. Resolution of syringomyelia is common following hindbrain decompression for Chiari malformation, yet little is known about the kinetics governing this process. The authors sought to establish the volumetric rate of syringomyelia resolution. Methods. A retrospective cohort of patients undergoing hindbrain decompression for a Chiari malformation Type I with preoperative cervical or thoracic syringomyelia was identified. Patients were included in the study if they had at least 3 neuroimaging studies that detailed the entirety of their preoperative syringomyelia over a minimum of 6 months postoperatively. The authors reconstructed the MR images in 3 dimensions and calculated the volume of the syringomyelia. They plotted the syringomyelia volume over time and constructed regression models using the method of least squares. The Akaike information criterion and Bayesian information criterion were used to calculate the relative goodness of fit. The coefficients of determination R-2 (unadjusted and adjusted) were calculated to describe the proportion of variability in each individual data set accounted for by the statistical model. Results. Two patients were identified as meeting inclusion criteria. Plots of the least-squares best fit were identified as 4.01459e(-0.0180804x) and 13.2556e(-0.00615859x). Decay of the syringomyelia followed an exponential model in both patients (R-2 = 0.989582 and 0.948864). Conclusions. Three-dimensional analysis of syringomyelia resolution over time enables the kinetics to be estimated. This technique is yet to be validated in a large cohort. Because syringomyelia is the final common pathway for a number of different pathological processes, it is possible that this exponential only applies to syringomyelia related to treatment of Chiari malformation Type I. (DOI: 10.3171/2011.6.FOCUS11106) C1 [Coumans, Jean-Valery; Walcott, Brian P.; Butler, William E.; Nahed, Brian V.; Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Coumans, Jean-Valery; Walcott, Brian P.; Butler, William E.; Nahed, Brian V.; Kahle, Kristopher T.] Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Institutes of Health) [UL1 RR 025758]; Harvard University FX This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Institutes of Health Award No. UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. The authors used the open-source software OsiriX Imaging Software for volumetric analysis. This open-source version does not have FDA 510(k) clearance for clinical use in the US. NR 22 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD SEP PY 2011 VL 31 IS 3 AR E4 DI 10.3171/2011.6.FOCUS11106 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 818PX UT WOS:000294767400005 PM 21882909 ER PT J AU Schanker, BD Walcott, BP Nahed, BV Kahle, KT Li, YM Coumans, JVCE AF Schanker, Benjamin D. Walcott, Brian P. Nahed, Brian V. Kahle, Kristopher T. Li, Yan Michael Coumans, Jean-Valery C. E. TI Familial Chiari malformation: case series SO NEUROSURGICAL FOCUS LA English DT Article DE Chiari malformation; familial; genetic; posterior fossa; cerebellum; surgery ID KLIPPEL-FEIL-SYNDROME; FEMALE MONOZYGOTIC TWINS; POSTERIOR CRANIAL FOSSA; I MALFORMATION; CRANIOFRONTONASAL SYNDROME; TONSILLAR ECTOPIA; 1ST-DEGREE RELATIVES; 2 SIBLINGS; SYRINGOMYELIA; MUTATIONS AB Chiari malformations (Types I-IV) are abnormalities of the posterior fossa that affect the cerebellum, brainstem, and the spinal cord with prevalence rates of 0.1%-0.5%. Case reports of familial aggregation of Chiari malformation, twin studies, cosegregation of Chiari malformation with known genetic conditions, and recent gene and genome-wide association studies provide strong evidence of the genetic underpinnings of familial Chiari malformation. The authors report on a series of 3 family pairs with Chiari malformation Type I: 2 mother-daughter pairs and 1 father-daughter pair. The specific genetic causes of familial Chiari malformation have yet to be fully elucidated. The authors review the literature and discuss several candidate genes. Recent advances in the understanding of the genetic influences and pathogenesis of familial Chiari malformation are expected to improve management of affected patients and monitoring of at-risk family members. (DOI: 10.3171/2011.6.FOCUS11104) C1 [Schanker, Benjamin D.; Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.; Coumans, Jean-Valery C. E.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Schanker, Benjamin D.; Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.; Coumans, Jean-Valery C. E.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Yan Michael] SUNY Syracuse, Upstate Med Univ, Dept Neurosurg, Syracuse, NY USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurol Surg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM bwalcott@partners.org NR 52 TC 7 Z9 7 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD SEP PY 2011 VL 31 IS 3 AR E1 DI 10.3171/2011.6.FOCUS11104 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 818PX UT WOS:000294767400002 PM 21882906 ER PT J AU Kirzhner, M Jakobiec, FA Kim, N AF Kirzhner, Maria Jakobiec, Frederick A. Kim, Nancy TI Focal Blue Nevus of the Eyelid Margin (Mucocutaneous Junction): A Report of a Unique Case With a Review of the Literature SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Review ID MICROPHTHALMIA TRANSCRIPTION FACTOR; CLINICOPATHOLOGICAL FEATURES; APOCRINE HIDROCYSTOMA; MALIGNANT-MELANOMA; CARNEY COMPLEX; CONJUNCTIVA; DIAGNOSIS; CARCINOMA; VARIANT AB Purpose: To describe the first isolated and focal benign blue nevus of the eyelid margin. Methods: Review of clinical, histopathologic, and immunohistochemical characteristics and relevant literature. Results: A 93-year-old Caucasian woman with a flat, irregular, and deeply pigmented black growth of the left upper eyelid margin of unknown duration underwent a full-thickness eyelid excisional biopsy. Microscopically, a population of loosely aggregated, mitotically inactive, heavily pigmented oval-to-elongated spindle dermal cells that paralleled the epithelium was seen. MART-1 and HMB-45 immunostaining of premelanosomes could not distinguish between melanocytes and melanophages. The more specific microphthalmia-associated transcription factor stained the nuclei of the subepithelial melanocytes before and after bleaching of the cytoplasmic melanin. The patient did not have Carney complex. No residual pigmentation or lesional recurrence has been noted during 6 months of follow up. Conclusions: A blue nevus of the preorbicularis eyelid skin is extremely rare, and still more uncommon is such a lesion of the eyelid margin. Careful microscopic and immunohistochemical evaluation is necessary to establish the proper diagnosis. Wide local excision should be performed due to concern about a more common and serious melanomatous nodule. A differential diagnosis of other pigmented lesions in this location is offered. (Ophthal Plast Reconstr Surg 2011;27:338-342) C1 [Kirzhner, Maria; Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Kim, Nancy] Massachusetts Eye & Ear Infirm, Oculoplast Serv, Boston, MA 02114 USA. [Kirzhner, Maria; Jakobiec, Frederick A.; Kim, Nancy] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Suite 321,243 Charles St,Room 321, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 38 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD SEP-OCT PY 2011 VL 27 IS 5 BP 338 EP 342 DI 10.1097/IOP.0b013e318213f743 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 817XS UT WOS:000294711700025 PM 21490517 ER PT J AU Sloan, DM Marx, BP Keane, TM AF Sloan, Denise M. Marx, Brian P. Keane, Terence M. TI Reducing the Burden of Mental Illness in Military Veterans: Commentary on Kazdin and Blase (2011) SO PERSPECTIVES ON PSYCHOLOGICAL SCIENCE LA English DT Article DE dissemination; implementation; telehealth ID POSTTRAUMATIC-STRESS-DISORDER; THERAPY; TRIAL; CARE AB Clinical psychology as a profession owes much to the recognition of the psychosocial needs of servicemen and women returning from World War II and the Korean conflict. The current conflicts in Iraq and Afghanistan represent another opportunity for substantial advancements in assessment and treatment practices. Stimulated by the prescient article by Kazdin and Blase (2011), we briefly describe innovations in evidence-based practices currently being implemented in the Veterans Health Administration to best serve the more than 2 million returning servicemen and women. The largest healthcare system in the nation, the U.S. Department of Veterans Affairs began a wide range of innovations early this century to include dissemination of evidence-based mental health treatments, the use of anonymous Internet-based interventions to reach large numbers of military personnel who may not otherwise present for mental health service, the use of videoconferencing to deliver assessment and treatment to individuals residing in remote locations, and the use of laypersons (e.g., peers) for treatment delivery. In addition to describing the strengths of these efforts to reduce mental health burden, we also discuss persisting barriers and limitations of these innovative efforts within this system of healthcare. C1 [Sloan, Denise M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM denise.sloan@va.gov NR 16 TC 8 Z9 8 U1 1 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1745-6916 EI 1745-6924 J9 PERSPECT PSYCHOL SCI JI Perspect. Psychol. Sci. PD SEP PY 2011 VL 6 IS 5 BP 503 EP 506 DI 10.1177/1745691611416995 PG 4 WC Psychology, Multidisciplinary SC Psychology GA 815ZH UT WOS:000294568000011 PM 26168203 ER PT J AU Carty, MJ Pribaz, JJ Antin, JH Volpicelli, ER Toomey, CE Farkash, EA Hochberg, EP AF Carty, Matthew J. Pribaz, Julian J. Antin, Joseph H. Volpicelli, Elgida R. Toomey, Christiana E. Farkash, Evan A. Hochberg, Ephraim P. TI A Patient Death Attributable to Implant-Related Primary Anaplastic Large Cell Lymphoma of the Breast SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID OF-THE-LITERATURE; CONNECTIVE-TISSUE DISEASES; NON-HODGKINS-LYMPHOMA; PROGNOSTIC-FACTORS; SILICONE IMPLANT; B-CELL; CAPSULE; RECONSTRUCTION; INVOLVEMENT; FEATURES AB Implant-related primary anaplastic large cell lymphoma (ALCL) of the breast is a rare clinical entity. With increasing attention being paid to this disease, most cases reported to date in the literature have demonstrated indolent clinical courses responsive to explantation, capsulectomy, chemotherapy, and/or radiotherapy. The authors describe a case of bilateral implant-related primary ALCL of the breast that proved refractory to both standard and aggressive interventions, ultimately resulting in patient death secondary to disease progression. The authors situate this case in the context of the current state of knowledge regarding implant-related primary ALCL of the breast and suggest that this entity is generally, but not universally, indolent in nature. (Plast. Reconstr. Surg. 128: 112e, 2011.) C1 [Carty, Matthew J.] Brigham & Womens Hosp, Faulkner Hosp, Div Plast Surg, Jamaica Plain, MA 02130 USA. Brigham & Womens Hosp, Dept Pathol, Jamaica Plain, MA 02130 USA. Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Carty, MJ (reprint author), Brigham & Womens Hosp, Faulkner Hosp, Div Plast Surg, 1153 Ctr St, Jamaica Plain, MA 02130 USA. EM mcarty@partners.org NR 35 TC 39 Z9 40 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP PY 2011 VL 128 IS 3 BP 112E EP 118E DI 10.1097/PRS.0b013e318221db96 PG 7 WC Surgery SC Surgery GA 812JB UT WOS:000294288100001 PM 21775924 ER PT J AU Magbanua, MJM Roy, R Sosa, EV Weinberg, V Federman, S Mattie, MD Hughes-Fulford, M Simko, J Shinohara, K Haqq, CM Carroll, PR Chan, JM AF Magbanua, Mark Jesus M. Roy, Ritu Sosa, Eduardo V. Weinberg, Vivian Federman, Scott Mattie, Michael D. Hughes-Fulford, Millie Simko, Jeff Shinohara, Katsuto Haqq, Christopher M. Carroll, Peter R. Chan, June M. TI Gene Expression and Biological Pathways in Tissue of Men with Prostate Cancer in a Randomized Clinical Trial of Lycopene and Fish Oil Supplementation SO PLOS ONE LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; ACTIVE SURVEILLANCE; OXIDATIVE STRESS; CELL-GROWTH; VITAMIN-E; CORONARY ATHEROSCLEROSIS; ARACHIDONIC-ACID; BETA-CAROTENE; DNA-DAMAGE AB Background: Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial. Methods: Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (n = 29) or fish oil (n = 27) supplementation or placebo (n = 28). Gene expression in morphologically normal prostate tissue was studied at baseline and at 3 months via cDNA microarray analysis. Differential gene expression and pathway analyses were performed to identify genes and pathways modulated by these micronutrients. Results: Global gene expression analysis revealed no significant individual genes that were associated with high intake of fish or tomato at baseline or after 3 months of supplementation with lycopene or fish oil. However, exploratory pathway analyses of rank-ordered genes (based on p-values not corrected for multiple comparisons) revealed the modulation of androgen and estrogen metabolism in men who routinely consumed more fish (p = 0.029) and tomato (p = 0.008) compared to men who ate less. In addition, modulation of arachidonic acid metabolism (p = 0.01) was observed after 3 months of fish oil supplementation compared with the placebo group; and modulation of nuclear factor (erythroid derived-2) factor 2 or Nrf2-mediated oxidative stress response for either supplement versus placebo (fish oil: p = 0.01, lycopene: p = 0.001). Conclusions: We did not detect significant individual genes associated with dietary intake and supplementation of lycopene and fish oil. However, exploratory analyses revealed candidate in vivo pathways that may be modulated by these micronutrients. C1 [Magbanua, Mark Jesus M.; Sosa, Eduardo V.; Federman, Scott; Mattie, Michael D.; Carroll, Peter R.; Chan, June M.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Roy, Ritu; Weinberg, Vivian] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr Biostat &, San Francisco, CA 94143 USA. [Hughes-Fulford, Millie; Simko, Jeff; Shinohara, Katsuto; Haqq, Christopher M.; Carroll, Peter R.; Chan, June M.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Hughes-Fulford, Millie] San Francisco VA Med Ctr, San Francisco, CA USA. [Simko, Jeff] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Chan, June M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Magbanua, MJM (reprint author), Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. EM JChan@urology.ucsf.edu FU NIH/NCI [RO1 R01CA101042]; Prostate Cancer Foundation FX NIH/NCI RO1 R01CA101042; Prostate Cancer Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 21 Z9 23 U1 4 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 1 PY 2011 VL 6 IS 9 AR e24004 DI 10.1371/journal.pone.0024004 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 817OO UT WOS:000294683900020 PM 21912659 ER PT J AU Young, RL Malcolm, KC Kret, JE Caceres, SM Poch, KR Nichols, DP Taylor-Cousar, JL Saavedra, MT Randell, SH Vasil, ML Burns, JL Moskowitz, SM Nick, JA AF Young, Robert L. Malcolm, Kenneth C. Kret, Jennifer E. Caceres, Silvia M. Poch, Katie R. Nichols, David P. Taylor-Cousar, Jennifer L. Saavedra, Milene T. Randell, Scott H. Vasil, Michael L. Burns, Jane L. Moskowitz, Samuel M. Nick, Jerry A. TI Neutrophil Extracellular Trap (NET)-Mediated Killing of Pseudomonas aeruginosa: Evidence of Acquired Resistance within the CF Airway, Independent of CFTR SO PLOS ONE LA English DT Article ID CYSTIC-FIBROSIS PATIENTS; RECOMBINANT HUMAN DNASE; GROUP-A STREPTOCOCCUS; PULMONARY-FUNCTION; YOUNG-CHILDREN; NONOPSONIC PHAGOCYTOSIS; STAPHYLOCOCCUS-AUREUS; ANTIBIOTIC-TREATMENT; GENETIC ADAPTATION; HUMAN-GRANULOCYTES AB The inability of neutrophils to eradicate Pseudomonas aeruginosa within the cystic fibrosis (CF) airway eventually results in chronic infection by the bacteria in nearly 80 percent of patients. Phagocytic killing of P. aeruginosa by CF neutrophils is impaired due to decreased cystic fibrosis transmembrane conductance regulator (CFTR) function and virulence factors acquired by the bacteria. Recently, neutrophil extracellular traps (NETs), extracellular structures composed of neutrophil chromatin complexed with granule contents, were identified as an alternative mechanism of pathogen killing. The hypothesis that NET-mediated killing of P. aeruginosa is impaired in the context of the CF airway was tested. P. aeruginosa induced NET formation by neutrophils from healthy donors in a bacterial density dependent fashion. When maintained in suspension through continuous rotation, P. aeruginosa became physically associated with NETs. Under these conditions, NETs were the predominant mechanism of killing, across a wide range of bacterial densities. Peripheral blood neutrophils isolated from CF patients demonstrated no impairment in NET formation or function against P. aeruginosa. However, isogenic clinical isolates of P. aeruginosa obtained from CF patients early and later in the course of infection demonstrated an acquired capacity to withstand NET-mediated killing in 8 of 9 isolates tested. This resistance correlated with development of the mucoid phenotype, but was not a direct result of the excess alginate production that is characteristic of mucoidy. Together, these results demonstrate that neutrophils can kill P. aeruginosa via NETs, and in vitro this response is most effective under non-stationary conditions with a low ratio of bacteria to neutrophils. NET-mediated killing is independent of CFTR function or bacterial opsonization. Failure of this response in the context of the CF airway may occur, in part, due to an acquired resistance against NET-mediated killing by CF strains of P. aeruginosa. C1 [Young, Robert L.; Malcolm, Kenneth C.; Kret, Jennifer E.; Caceres, Silvia M.; Poch, Katie R.; Nichols, David P.; Taylor-Cousar, Jennifer L.; Saavedra, Milene T.; Nick, Jerry A.] Natl Jewish Hlth, Dept Med, Denver, CO USA. [Nichols, David P.; Taylor-Cousar, Jennifer L.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Young, Robert L.; Taylor-Cousar, Jennifer L.; Saavedra, Milene T.; Nick, Jerry A.] Univ Colorado, Denver Sch Med, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Nichols, David P.] Univ Colorado, Denver Sch Med, Dept Pediat, Aurora, CO USA. [Randell, Scott H.] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC USA. [Vasil, Michael L.] Univ Colorado, Denver Sch Med, Dept Microbiol, Aurora, CO USA. [Burns, Jane L.] Univ Washington, Sch Med, Dept Pediat, Seattle Childrens Hosp,Div Pediat Infect Dis, Seattle, WA 98195 USA. [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, Boston, MA USA. RP Young, RL (reprint author), Natl Jewish Hlth, Dept Med, Denver, CO USA. EM rlyoung630@gmail.com FU Cystic Fibrosis Foundation [YOUNG08Q0]; Rebecca Runyon Bryan Chair for Cystic Fibrosis; Max and Yetta Karasik Foundation; National Institutes of Health (NIH) [1R01HL090991, R37AI15940, P30DK065988] FX Support for this work was provided by the Cystic Fibrosis Foundation (YOUNG08Q0), the Rebecca Runyon Bryan Chair for Cystic Fibrosis, the Max and Yetta Karasik Foundation, the National Institutes of Health (NIH) 1R01HL090991 to JAN, NIH R37AI15940 to MLV, and NIH P30DK065988 to SHR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 86 TC 79 Z9 83 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 1 PY 2011 VL 6 IS 9 AR e23637 DI 10.1371/journal.pone.0023637 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 817OO UT WOS:000294683900006 PM 21909403 ER PT J AU Bhushan, A Leigh, JP AF Bhushan, Abhinav Leigh, J. Paul TI National Trends in Occupational Injuries Before and After 1992 and Predictors of Workers' Compensation Costs SO PUBLIC HEALTH REPORTS LA English DT Article ID BUSINESS-CYCLE; RATES; DECLINE AB Objective. Numbers and costs of occupational injuries and illnesses are significant in terms of morbidity and dollars, yet our understanding of time trends is minimal. We investigated trends and addressed some common hypotheses regarding causes of fluctuations. Methods. We pulled data on incidence rates (per 100 full-time employed workers) for injuries and illnesses from the U.S. Bureau of Labor Statistics and on costs and benefits from the National Academy of Social Insurance for 1973 through 2007. Rates reflected all injury and illness cases, lost work-time cases, and cases resulting in at least 31 days away from work. We adjusted dollar costs (premiums) and benefits for inflation and measured them per employed worker. We plotted data in time-trend charts and ran linear regressions. Results. From 1973 to 1991, there was a weak to nonexistent downward trend for injury and illness rates, and rates were strongly and negatively correlated with the unemployment rate. From 1992 to 2007, there were strong, consistent downward trends, but no longer were there statistically significant correlations with unemployment. Significant predictors (and signs) of workers' compensation premiums for 1973-2007 included medical price inflation (positive), number of lost-time injuries (positive), the Dow Jones Industrial Average (negative), and inflation-adjusted interest rate on U.S. Treasury bonds (negative). Dollars of benefits were positively and significantly predicted by medical inflation and number of lost-time cases. For 1992-2007, the Dow Jones variable was the only robust predictor of premiums; the number of injuries was not a significant positive predictor. Conclusion. We had two major conclusions. First, the year 1992 marked a sharp contrast in trends and correlations between unemployment and incidence rates for occupational injuries and illnesses. Second, for the entire time period (1973-2007), insurance carriers' premiums were strongly associated with returns on investments. C1 [Leigh, J. Paul] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Ctr Healthcare Policy & Res, Davis, CA 95616 USA. [Bhushan, Abhinav] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Leigh, JP (reprint author), Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Ctr Healthcare Policy & Res, 1 Shields Ave, Davis, CA 95616 USA. EM pleigh@ucdavis.edu RI Leigh, J. Paul/I-5772-2013 FU National Institute for Occupational Safety and Health (NIOSH) [OH008248-01] FX Partial support for this research came from the National Institute for Occupational Safety and Health (NIOSH) (OH008248-01). The findings and conclusions in this article are those of the authors and do not necessarily represent the views of NIOSH. NR 28 TC 5 Z9 5 U1 1 U2 9 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2011 VL 126 IS 5 BP 625 EP 634 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 816BM UT WOS:000294573700005 PM 21886322 ER PT J AU Mimiaga, MJ Johnson, CV Reisner, SL VanDerwarker, R Mayer, KH AF Mimiaga, Matthew J. Johnson, Carey V. Reisner, Sari L. VanDerwarker, Rodney Mayer, Kenneth H. TI Barriers to Routine HIV Testing Among Massachusetts Community Health Center Personnel SO PUBLIC HEALTH REPORTS LA English DT Article ID FOR-DISEASE-CONTROL; HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; REVISED RECOMMENDATIONS; CARE SETTINGS; SAN-FRANCISCO; PREVENTION; PREVALENCE; WOMEN AB Objectives. We assessed the extent to which Centers for Disease Control and Prevention (CDC) recommendations have influenced routine HIV testing among Massachusetts community health center (CHC) personnel, and identified specific barriers and facilitators to routine testing. Methods. Thirty-one CHCs were enrolled in the study. We compared those that did and did not receive funding support from the federal Ryan White HIV/AIDS Program. An anonymous survey was administered to a maximum five personnel from each CHC, including a senior administrator, the medical director, and three medical providers. Overall, 137 participants completed the survey. Results. Among all CHCs, 53% of administrators reported having implemented routine HIV testing at their CHCs; however, only 33% of medical directors/providers reported having implemented routine HIV testing in their practices (p<0.05). Among administrators, 60% of those from Ryan White-supported CHCs indicated that both they and their CHCs were aware of CDC's recommendations, compared with 27% of administrators from non-Ryan White-supported CHCs. The five most frequently reported barriers to the implementation of routine HIV testing were (1) constraints on providers' time (68%), (2) time required to administer counseling (65%), (3) time required to administer informed consent (52%), (4) lack of funding (35%), and (5) need for additional training (34%). In a multivariable logistic regression model, the provision of onsite HIV testing by nonmedical staff resulted in increased odds of conducting routine HIV testing (odds ratio [OR] = 9.84, 95% confidence interval [Cl] 1.77, 54.70). However, the amount of time needed to administer informed consent was associated with decreased odds of providing routine testing (OR=0.21, 95% CI 0.05, 0.92). Conclusions. Routine HIV testing is not currently being implemented uniformly among Massachusetts CHCs. Future efforts to increase implementation should address personnel concerns regarding time and staff availability. C1 [Mimiaga, Matthew J.; Johnson, Carey V.; Reisner, Sari L.; VanDerwarker, Rodney; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Warren Alpert Sch Med, Providence, RI USA. RP Mimiaga, MJ (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St, Boston, MA 02215 USA. EM mmimiaga@fenwayhealth.org FU Gilead Sciences, Inc. [2691] FX This project was supported by a Testing and Linkage to Care grant (#2691) from Gilead Sciences, Inc. awarded to Drs. Mayer and Mimiaga, who exercised full control over the project. The content is solely the responsibility of the authors and does not necessarily represent the official view of Gilead Science, Inc. NR 38 TC 12 Z9 12 U1 1 U2 4 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 2011 VL 126 IS 5 BP 643 EP 652 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 816BM UT WOS:000294573700007 PM 21886324 ER PT J AU Lee, JH Gosselin, F Wynn, JK Green, MF AF Lee, Junghee Gosselin, Frederic Wynn, Jonathan K. Green, Michael F. TI How Do Schizophrenia Patients Use Visual Information to Decode Facial Emotion? SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; emotional face recognition; spatial frequency; bubbles tasks; potent information; strategy ID GENERALIZED POOR PERFORMANCE; AFFECT RECOGNITION; AFFECTIVE PROSODY; PERCEPTION; EXPRESSIONS; FACES; IMPAIRMENT; DEFICITS AB Impairment in recognizing facial emotions is a prominent feature of schizophrenia patients, but the underlying mechanism of this impairment remains unclear. This study investigated the specific aspects of visual information that are critical for schizophrenia patients to recognize emotional expression. Using the Bubbles technique, we probed the use of visual information during a facial emotion discrimination task (fear vs. happy) in 21 schizophrenia patients and 17 healthy controls. Visual information was sampled through randomly located Gaussian apertures (or "bubbles") at 5 spatial frequency scales. Online calibration of the amount of face exposed through bubbles was used to ensure 75% overall accuracy for each subject. Least-square multiple linear regression analyses between sampled information and accuracy were performed to identify critical visual information that was used to identify emotional expression. To accurately identify emotional expression, schizophrenia patients required more exposure of facial areas (i.e., more bubbles) compared with healthy controls. To identify fearful faces, schizophrenia patients relied less on bilateral eye regions at high-spatial frequency compared with healthy controls. For identification of happy faces, schizophrenia patients relied on the mouth and eye regions; healthy controls did not utilize eyes and used the mouth much less than patients did. Schizophrenia patients needed more facial information to recognize emotional expression of faces. In addition, patients differed from controls in their use of high-spatial frequency information from eye regions to identify fearful faces. This study provides direct evidence that schizophrenia patients employ an atypical strategy of using visual information to recognize emotional faces. C1 [Lee, Junghee; Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Lee, Junghee; Wynn, Jonathan K.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gosselin, Frederic] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. RP Lee, JH (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. EM jungheelee@ucla.edu RI Lee, Junghee/C-5226-2014; Wynn, Jonathan/H-3749-2014 OI Lee, Junghee/0000-0001-9567-8700; Wynn, Jonathan/0000-0002-1763-8540 FU National Institute of Mental Health [MH 43929] FX National Institute of Mental Health Grant MH 43929 (PI: M.F.G.). NR 46 TC 22 Z9 23 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD SEP PY 2011 VL 37 IS 5 BP 1001 EP 1008 DI 10.1093/schbul/sbq006 PG 8 WC Psychiatry SC Psychiatry GA 815VC UT WOS:000294557100019 PM 20156852 ER PT J AU Chang, BH Sommers, E AF Chang, Bei-Hung Sommers, Elizabeth TI Acupuncture and the relaxation response for treating gastrointestinal symptoms in HIV patients on highly active antiretroviral therapy SO ACUPUNCTURE IN MEDICINE LA English DT Article ID QUALITY-OF-LIFE; POSTOPERATIVE NAUSEA; CLINICAL-TRIALS; NITRIC-OXIDE; MISSING DATA; STIMULATION; COHORT; DISCONTINUATION; PLACEBO; REGIMEN AB Objectives To examine the effect of acupuncture and the relaxation response (RR) for treating gastrointestinal (GI) symptoms in HIV patients who are using highly active antiretroviral therapy (HAART). Methods The authors conducted a 4-arm 2x2 double-blind randomised controlled trial in an acupuncture clinic in the USA. Sham acupuncture and health education were used as the control conditions of real acupuncture and RR elicitation, respectively. Enrolled patients were randomised to real acupuncture + RR (AR), sham acupuncture + RR (SR), real acupuncture + health education (AE) or sham acupuncture + health education (SE) study arm. Participants listened to CDs with RR-eliciting instructions or health education while receiving acupuncture intervention. Interventions were provided twice weekly for 4 weeks and once weekly for another 4 weeks. Participants used daily diaries to record GI symptom severity ratings (0-10). The authors estimated the intervention effect as the changes in symptom rating per intervention session increase using a mixed-effects regression model. Results A total of 130 people with HIV/AIDS who were on HAART and had persistent GI symptoms were enrolled and 115 started the study intervention. The AR group had greater intervention effects for loose stools symptoms than the other three groups (beta=-0.149, -0.151 and -0.144, p value=0.013, 0.013 and 0.018 comparing AR to AE, SR and SE, respectively). The AR group also had significant intervention effects on reducing nausea symptoms when the intervention was given twice per week (beta=-0.218, p=0.001). Conclusions Our trial provided preliminary data demonstrating the potential synergistic effects of acupuncture and RR for treating GI symptoms in HIV patients on HAART. C1 [Chang, Bei-Hung] VA Boston Hlth Care Syst, Boston, MA 02130 USA. [Chang, Bei-Hung] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Sommers, Elizabeth] Pathways Wellness AIDS Care Project, Boston, MA USA. RP Chang, BH (reprint author), VA Boston Hlth Care Syst, 150 S Huntington Ave,152H, Boston, MA 02130 USA. EM bhchang@bu.edu RI cmu, library/L-1810-2013 FU Center for Complementary and Alternative Medicine, National Institutes of Health [R21 AT003377] FX The study was funded by the Center for Complementary and Alternative Medicine, National Institutes of Health: Grant number R21 AT003377. NR 55 TC 2 Z9 2 U1 2 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-5284 J9 ACUPUNCT MED JI Acupunct. Med. PD SEP PY 2011 VL 29 IS 3 BP 180 EP 187 DI 10.1136/acupmed-2011-010026 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 812XL UT WOS:000294326700005 PM 21705396 ER PT J AU Bosworth, HB Granger, BB Mendys, P Brindis, R Burkholder, R Czajkowski, SM Daniel, JG Ekman, I Ho, M Johnson, M Kimmel, SE Liu, LZ Musaus, J Shrank, WH Buono, EW Weiss, K Granger, CB AF Bosworth, Hayden B. Granger, Bradi B. Mendys, Phil Brindis, Ralph Burkholder, Rebecca Czajkowski, Susan M. Daniel, Jodi G. Ekman, Inger Ho, Michael Johnson, Mimi Kimmel, Stephen E. Liu, Larry Z. Musaus, John Shrank, William H. Buono, Elizabeth Whalley Weiss, Karen Granger, Christopher B. TI Medication adherence: A call for action SO AMERICAN HEART JOURNAL LA English DT Article ID BLOOD-PRESSURE CONTROL; RANDOMIZED CONTROLLED-TRIAL; PRESCRIPTION DRUG LABELS; NURSE FOLLOW-UP; PHYSICIAN COMMUNICATION; TREATMENT OUTCOMES; PATIENT ADHERENCE; ELDERLY-PATIENTS; HEALTH LITERACY; AUTOMATED CALLS AB Poor adherence to efficacious cardiovascular-related medications has led to considerable morbidity, mortality, and avoidable health care costs. This article provides results of a recent think-tank meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (Food and Drug Administration, National Institutes of Health, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication nonadherence. (Am Heart J 2011;162:412-24.) C1 [Bosworth, Hayden B.] Durham VAMC, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Bosworth, Hayden B.] Duke Univ, Sch Nursing, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Mendys, Phil] UNC, Sch Pharm, Pfizer, US Med Affairs, Chapel Hill, NC USA. [Mendys, Phil] UNC, Sch Pharm, Div Cardiol, Chapel Hill, NC USA. [Brindis, Ralph] Oakland Kaiser Hosp, Amer Coll Cardiol, San Francisco, CA USA. [Brindis, Ralph] Oakland Kaiser Hosp, Dept Cardiol, San Francisco, CA USA. [Burkholder, Rebecca; Johnson, Mimi] Natl Consumers League, Washington, DC USA. [Czajkowski, Susan M.] Natl Inst Heart Lung & Blood Inst, NIH, Bethesda, MD USA. [Daniel, Jodi G.] US Dept HHS, Office Natl Coordinator Hlth Informat Technol, Washington, DC 20201 USA. [Ekman, Inger] Gothenburg Univ, Sahlgrenska Acad, Ctr Person Ctr Care Long Term Illness GPCC, S-41124 Gothenburg, Sweden. [Ho, Michael] Denver VA Med Ctr, Denver, CO USA. [Kimmel, Stephen E.] Univ Penn, Sch Med, Div Cardiol, Dept Med & Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Liu, Larry Z.] Pfizer Inc, New York, NY USA. [Liu, Larry Z.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Musaus, John; Buono, Elizabeth Whalley] MWV Healthcare, Richmond, VA USA. [Shrank, William H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA. [Weiss, Karen] US FDA, Washington, DC 20204 USA. [Granger, Christopher B.] Duke Univ, Div Cardiol, Dept Med, Durham, NC 27705 USA. [Bosworth, Hayden B.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27705 USA. RP Bosworth, HB (reprint author), Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, 2424 Erwin Rd,Suite 1105,Hock Plaza, Durham, NC 27705 USA. EM hayden.bosworth@duke.edu RI Granger, Christopher/D-3458-2014 OI Granger, Christopher/0000-0002-0045-3291 FU VA HSRD career scientist award [RCS 08-027]; American Heart Association; NIH [UL1RR024128] FX This research is supported by a VA HSRD career scientist award (RCS 08-027) and an Established Investigator Award from the American Heart Association to the first author (H. B. B.). Dr. B. Granger was supported by A NIH funded CTSA grant (UL1RR024128). The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 84 TC 80 Z9 86 U1 7 U2 27 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2011 VL 162 IS 3 BP 412 EP 424 DI 10.1016/j.ahj.2011.06.007 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 814JU UT WOS:000294447400002 PM 21884856 ER PT J AU Kapoor, JR Fonarow, GC Zhao, X Kapoor, R Hernandez, AF Heidenreich, PA AF Kapoor, John R. Fonarow, Gregg C. Zhao, Xin Kapoor, Roger Hernandez, Adrian F. Heidenreich, Paul A. TI Diabetes, quality of care, and in-hospital outcomes in patients hospitalized with heart failure SO AMERICAN HEART JOURNAL LA English DT Article ID INITIATE LIFESAVING TREATMENT; CLINICAL-OUTCOMES; ORGANIZED PROGRAM; OPTIMIZE-HF; CONTROLLED-TRIAL; RISK-FACTORS; ASSOCIATION; CARVEDILOL; METOPROLOL; MORTALITY AB Background Diabetes mellitus is frequently comorbid with heart failure (HF). It is unclear if comorbid diabetes is associated with quality of care and in-hospital mortality. Methods We analyzed 133,971 HF admissions from 431 hospitals between January 2005 and January 2010 comparing patients with and without diabetes. Results There were 54,352 (41%) patients hospitalized with HF with a history or newly diagnosed diabetes. After adjustment, patients with diabetes were as likely as patients without diabetes to appropriately receive the composite of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blockers (odds ratio [OR] 0.99, 95% CI 0.94-1.04), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (OR 0.98, 95% CI 0.92-1.05), evidence-based beta-blockers (OR 1.04, 95% CI 0.98-1.1), and hydralazine/nitrates (OR 1.09, 95% CI 0.99-1.2). However, patients with diabetes were less likely to receive smoking cessation counseling (OR 0.89, 95% CI 0.81-0.98) and blood pressure control (OR 0.81, 95% CI 0.78-0.84) and to attain the all-or-none composite measure (OR 0.96, 95% CI 0.93-0.99). Patients with diabetes were more likely to receive an aldosterone antagonist for reduced left ventricular ejection fraction (OR 1.05, 95% CI 1.00-1.11), lipid-lowering agent (OR 1.33, 95% CI 1.26-1.41), and influenza vaccination (OR 1.05, 95% CI 1.01-1.09). Diabetes was independently associated with longer hospital stay but not within-hospital mortality. Conclusions With few exceptions, the application of evidence-based care and in-hospital outcomes were similar whether or not diabetes was present in this large contemporary cohort of patients hospitalized with HF. (Am Heart J 2011;162:480-486.e3.) C1 [Kapoor, John R.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60031 USA. [Zhao, Xin; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Kapoor, Roger] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Heidenreich, Paul A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Fonarow, Gregg C.] Ahmanson Univ Calif Los Angeles, Cardiomyopathy Ctr, Los Angeles, CA USA. RP Kapoor, JR (reprint author), Univ Chicago, Pritzker Sch Med, 5841 S Maryland Ave, Chicago, IL 60031 USA. RI Hernandez, Adrian F./A-7818-2016 OI Heidenreich, Paul/0000-0001-7730-8490; Hernandez, Adrian F./0000-0003-3387-9616 FU Research Johnson & Johnson, Proventys; Amylin; Medtronic; Research National Heart, Lung, and Blood Institute; Ortho-McNeil; American Heart Association Pharmaceutical Roundtable; GlaxoSmithKline FX John Kapoor, Roger Kapoor, and Xin Zhao have no conflicts of interest. Adrian Hernandez was supported by Research Johnson & Johnson, Proventys, and Amylin; Paul Heidenreich received a grant from Medtronic. Gregg Fonarow has received funding from Research National Heart, Lung, and Blood Institute and a consultant of Novartis, Medtronic, and Scios.; Program disclosure: GWTG-HF program is provided by the American Heart Association. The GWTG-HF program is currently supported in part by Medtronic, Ortho-McNeil, and the American Heart Association Pharmaceutical Roundtable and, in the past, through support from GlaxoSmithKline. NR 24 TC 6 Z9 6 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2011 VL 162 IS 3 BP 480 EP U95 DI 10.1016/j.ahj.2011.06.008 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 814JU UT WOS:000294447400010 PM 21884864 ER PT J AU Hochholzer, W Trenk, D Mega, JL Morath, T Stratz, C Valina, CM O'Donoghue, ML Bernlochner, I Contant, CF Guo, JP Sabatine, MS Schomig, A Neumann, FJ Kastrati, A Wiviott, SD Sibbing, D AF Hochholzer, Willibald Trenk, Dietmar Mega, Jessica L. Morath, Tanja Stratz, Christian Valina, Christian M. O'Donoghue, Michelle L. Bernlochner, Isabell Contant, Charles F. Guo, Jianping Sabatine, Marc S. Schoemig, Albert Neumann, Franz-Josef Kastrati, Adnan Wiviott, Stephen D. Sibbing, Dirk TI Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after loading dose and on maintenance therapy SO AMERICAN HEART JOURNAL LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; OF-FUNCTION POLYMORPHISM; PLATELET-AGGREGATION; ACTIVE METABOLITE; CIGARETTE-SMOKING; EXTRINSIC FACTORS; STENT THROMBOSIS; INHIBITION; ASSOCIATION; REACTIVITY AB Background Pharmacodynamic studies reported an amplified on-clopidogrel platelet inhibition in smokers potentially caused by an increased metabolic drug activation via induction of cytochrome P450 1A2. The aims of this analysis were to evaluate the impact of smoking on the antiplatelet effect of clopidogrel and prasugrel and to test the potential interaction of smoking with the treatment effect of these drugs. Methods A variety of platelet function results was analyzed from 2 large cohorts of patients undergoing coronary intervention after loading with clopidogrel 600 mg (n = 2,533 and n = 1,996), a cohort of patients undergoing dose adaptation from 75 to 150 mg according to response to clopidogrel (n = 117) and a crossover trial comparing clopidogrel 150 mg with prasugrel 10 mg (n = 87). Linear regression analyses were used to test the impact of smoking on platelet function and to identify independent predictors of on-treatment platelet reactivity. The potential interaction of smoking with the clinical effect of clopidogrel versus prasugrel was analyzed in the TRITON-TIMI 38 cohort (n = 13,608). Results No significant association of smoking with platelet reactivity on clopidogrel was seen in unadjusted and adjusted analyses. The variables most consistently associated with on-clopidogrel platelet function were age, sex, diabetes, and body mass index. There was no significant interaction of smoking status at presentation with the clinical efficacy of prasugrel versus clopidogrel (P for interaction = .39). Conclusions Smoking does not impact on platelet reactivity in patients after loading or on different maintenance doses of clopidogrel. The clinical treatment effect of clopidogrel versus prasugrel is not affected by smoking status at presentation. (Am Heart J 2011;162:518-526.e5.) C1 [Hochholzer, Willibald; Mega, Jessica L.; O'Donoghue, Michelle L.; Contant, Charles F.; Guo, Jianping; Sabatine, Marc S.; Wiviott, Stephen D.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, Boston, MA 02115 USA. [Hochholzer, Willibald; Mega, Jessica L.; O'Donoghue, Michelle L.; Contant, Charles F.; Guo, Jianping; Sabatine, Marc S.; Wiviott, Stephen D.] Harvard Univ, Sch Med, Boston, MA USA. [Hochholzer, Willibald; Trenk, Dietmar; Stratz, Christian; Valina, Christian M.; Neumann, Franz-Josef] Herz Zentrum Bad Krozingen, Bad Krozingen, Germany. [Morath, Tanja; Bernlochner, Isabell; Schoemig, Albert; Kastrati, Adnan; Sibbing, Dirk] Tech Univ Munich, Deutsch Herzzentrum, Munich, Germany. [Morath, Tanja; Bernlochner, Isabell; Schoemig, Albert; Kastrati, Adnan; Sibbing, Dirk] Tech Univ Munich, Med Klin Rechts Isar 1, Munich, Germany. RP Hochholzer, W (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM whochholzer@partners.org FU Sanofi-Aventis; Roche Diagnostics; AstraZeneca; Eli Lilly; Daiichi Sankyo; Bayer Healthcare; Bristol-Myers Squibb; Johnson Johnson; Novartis; Eisai; Bristol-Myers Squibb/Sanofi-Aventis Joint Venture; Daiichi-Sankyo; Daiichi-Sankyo/Lilly FX Dr Hochholzer reported receiving consultant fees from Sanofi-Aventis and research grants from Roche Diagnostics. Dr Trenk reported receiving lecture fees from AstraZeneca, Eli Lilly, and Daiichi Sankyo; honoraria for serving on the advisory boards of AstraZeneca, Eli Lilly, and Daiichi Sankyo; and research grants from Eli Lilly. Dr Mega reported receiving research grants from Bayer Healthcare, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Johnson & Johnson, and Sanofi-Aventis; research supplies from Accumetrics and Nanosphere; consulting fees from AstraZeneca, Bristol-Myers Squibb, and Sanofi-Aventis; and lecture fees from Novartis. Dr O'Donoghue reported receiving honoraria for CME from Eli Lilly and Daiichi Sankyo and research grants from Eisai. Dr Sabatine reported research grants from AstraZeneca, Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, and Daiichi-Sankyo; and scientific advisory board fees from Bristol-Myers Squibb/Sanofi-Aventis Joint Venture, Sanofi-Aventis, and Daiichi-Sankyo/Lilly Partnership. Dr Wiviott reported receiving research grants from Eli Lilly, Daiichi Sankyo, and Sanofi-Aventis and consulting fees or paid advisory board fees from Sanofi-Aventis and lecture fees from Eli Lilly and Daiichi Sankyo. Dr Sibbing reported receiving speaker fees from the Medicines Company and Dynabyte and fees for advisory board activities from Astra Zeneca and Eli Lilly. For all other authors: Conflict of Interest: none declared. NR 37 TC 36 Z9 36 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2011 VL 162 IS 3 BP 518 EP U142 DI 10.1016/j.ahj.2011.06.005 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 814JU UT WOS:000294447400016 PM 21884870 ER PT J AU Rienstra, M Cheng, S Larson, MG McCabe, EL Booth, SL Jacques, PF Lubitz, SA Yin, XY Levy, D Magnani, JW Ellinor, PT Benjamin, EJ Wang, TJ AF Rienstra, Michiel Cheng, Susan Larson, Martin G. McCabe, Elizabeth L. Booth, Sarah L. Jacques, Paul F. Lubitz, Steven A. Yin, Xiaoyan Levy, Daniel Magnani, Jared W. Ellinor, Patrick T. Benjamin, Emelia J. Wang, Thomas J. TI Vitamin D status is not related to development of atrial fibrillation in the community SO AMERICAN HEART JOURNAL LA English DT Article ID NEGATIVE ENDOCRINE REGULATOR; CONGESTIVE-HEART-FAILURE; RENIN-ANGIOTENSIN SYSTEM; BLOOD-PRESSURE; 1,25-DIHYDROXYVITAMIN D-3; D DEFICIENCY; RISK; 25-HYDROXYVITAMIN-D; POPULATION; DISEASE AB Background Atrial fibrillation (AF) is common and is an important cause of cardiovascular morbidity and mortality. Vitamin D is an emerging risk factor in cardiovascular disease, and vitamin D status is modifiable. Thus, we sought to investigate whether vitamin D status predisposed to the development of AF in a community-based sample. Methods We evaluated the relation between vitamin D status and development of AF in 2,930 participants of the Framingham Heart Study, Massachusetts, USA, without prevalent AF. The mean age was 65 +/- 11 years, and 56% were women. Vitamin D status was assessed by measuring 25-hydroxyvitamin D (25[OH] D) concentrations. Multivariable Cox regression models were adjusted for AF risk factors and season. Results During a mean follow-up of 9.9 years, 425 participants (15%) developed AF. In Cox proportional hazards models, 25(OH) D was not associated with development of AF, with a multivariable-adjusted hazard ratio of 0.99 per SD increment in 25(OH) D levels (95% CI 0.88-1.10, P = .81). Also, no relation was found in models including 25(OH) D as a dichotomous variable (above and below the cohort-specific 20th percentile; P = .59). Conclusion In our community-based sample, vitamin D status was not related to incident AF. Our data suggest that vitamin D deficiency does not promote the development of AF in the ambulatory setting. (Am Heart J 2011;162:538-41.) C1 [Rienstra, Michiel; Ellinor, Patrick T.; Wang, Thomas J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Rienstra, Michiel; Cheng, Susan; Larson, Martin G.; Yin, Xiaoyan; Levy, Daniel; Magnani, Jared W.; Benjamin, Emelia J.; Wang, Thomas J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Rienstra, Michiel; Cheng, Susan; Larson, Martin G.; Yin, Xiaoyan; Levy, Daniel; Magnani, Jared W.; Benjamin, Emelia J.; Wang, Thomas J.] NHLBI, Framingham, MA USA. [Cheng, Susan; McCabe, Elizabeth L.; Lubitz, Steven A.; Ellinor, Patrick T.; Wang, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Cheng, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med,Dept Med, Boston, MA 02114 USA. [Larson, Martin G.; Yin, Xiaoyan] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Booth, Sarah L.; Jacques, Paul F.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Div Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. RP Wang, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org OI Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU National Institutes of Health [NO1-HC-25195, K23-HL-074077, R01-AG14759, K23-RR-017376-04, K24-HL-04334, 1R01HL092577, 1RC1HL101056, 1R01HL102214, 6R01-NS 17950, R01AG028321, 5R21DA027021, 5RO1HL104156, 1K24HL105780]; US Department of Agriculture [58-1950-4-401]; American Heart Association; Netherlands Organization for Scientific Research [825.09.020]; Ellison Foundation; American Heart Association [09FTF2190028]; Evans Center for Interdisciplinary Biomedical Research ARC at Boston University FX This work was supported by grants from the National Institutes of Health (NO1-HC-25195, K23-HL-074077, R01-AG14759, K23-RR-017376-04, and K24-HL-04334; 1R01HL092577; 1RC1HL101056; 1R01HL102214; 6R01-NS 17950; 1R01HL092577; R01AG028321; 5R21DA027021; 5RO1HL104156; 1K24HL105780), the US Department of Agriculture (agreement 58-1950-4-401), and the American Heart Association. Dr Rienstra is supported by a grant from the Netherlands Organization for Scientific Research (Rubicon Grant 825.09.020). Dr Cheng is supported by a grant from the Ellison Foundation. Dr Magnani is supported by American Heart Association Award 09FTF2190028. This work was partially supported by the Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation Initiative at Boston University. NR 31 TC 24 Z9 25 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2011 VL 162 IS 3 BP 538 EP 541 DI 10.1016/j.ahj.2011.06.013 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 814JU UT WOS:000294447400019 PM 21884873 ER PT J AU Gao, X Chen, HL Schwarzschild, MA Ascherio, A AF Gao, Xiang Chen, Honglei Schwarzschild, Michael A. Ascherio, Alberto TI A Prospective Study of Bowel Movement Frequency and Risk of Parkinson's Disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE constipation; Parkinson disease; prospective studies ID BRAIN PATHOLOGY; NERVOUS-SYSTEM; LATE-LIFE; QUESTIONNAIRE; CONSTIPATION; CONSUMPTION AB The authors prospectively examined bowel movement frequency at baseline in relation to future Parkinson's disease risk in the Health Professionals Follow-up Study (HPFS) during 2000-2006 (33,901 men) and the Nurses' Health Study (NHS) during 1982-2006 (93,767 women). During the follow-up (6 years for the HPFS and 24 years for the NHS), the authors identified 156 incident male Parkinson's disease cases (HPFS) and 402 female cases (NHS). In the HPFS, compared with men with daily bowel movements, men with a bowel movement every 3 days or less had a multivariate-adjusted relative risk of 4.98 (95% confidence interval (CI): 2.59, 9.57) for developing Parkinson's disease in the next 6 years. In the NHS, the corresponding relative risk was 2.15 (95% CI: 0.76, 6.10), and the risk of Parkinson's disease was not elevated beyond 6 years of follow-up (relative risks = 1.25 for years 7-12, 0.54 for years 13-18, and 0.88 for years 19-24). When these 2 cohorts were combined, the pooled relative risks for Parkinson's disease in the next 6 years were 0.75, 1 (referent), 2.62, and 3.93 (95% CI: 2.26, 6.84) (P(trend) < 0.0001) across 4 bowel movement categories. In conclusion, infrequent bowel movements may antedate the onset of cardinal motor symptoms of Parkinson's disease and may contribute to the identification of populations with higher than average Parkinson's disease risk. C1 [Gao, Xiang; Ascherio, Alberto] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Gao, X (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM xiang.gao@channing.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU National Institutes of Health [R01 NS048517, R01 NS061858, K24NS060991]; National Institute of Environmental Health Sciences [Z01-ES-101986] FX The study was supported by National Institutes of Health grants R01 NS048517, R01 NS061858, and K24NS060991 and, in part, by grant Z01-ES-101986 from the intramural research program of the National Institute of Environmental Health Sciences. NR 24 TC 22 Z9 23 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2011 VL 174 IS 5 BP 546 EP 551 DI 10.1093/aje/kwr119 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 813HG UT WOS:000294356800007 PM 21719744 ER PT J AU Ohno, MS Sparks, TN Cheng, YW Caughey, AB AF Ohno, Mika S. Sparks, Teresa N. Cheng, Yvonne W. Caughey, Aaron B. TI Treating mild gestational diabetes mellitus: a cost-effectiveness analysis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2011 CL San Francisco, CA SP Soc Maternal Fetal Med DE cost-effectiveness; decision analysis; gestational diabetes mellitus ID SERVICES TASK-FORCE; PREGNANCY OUTCOMES; WOMENS PREFERENCES; CESAREAN DELIVERY; MACROSOMIA; DIAGNOSIS; INFANTS AB OBJECTIVE: This study investigated the cost-effectiveness of treating mild gestational diabetes mellitus (GDM). STUDY DESIGN: A decision analytic model was built to compare treating vs not treating mild GDM. The primary outcome was the incremental cost per quality-adjusted life year (QALY). All probabilities, costs, and benefits were derived from the literature. Base case, sensitivity analyses, and a Monte Carlo simulation were performed. RESULTS: Treating mild GDM was more expensive, more effective, and cost-effective at $20,412 per QALY. Treatment remained cost-effective when the incremental cost to treat GDM was less than $3555 or if treatment met at least 49% of its reported efficacy at the baseline cost to treat of $1786. CONCLUSION: Treating mild GDM is cost-effective in terms of improving maternal and neonatal outcomes including decreased rates of preeclampsia, cesarean sections, macrosomia, shoulder dystocia, permanent and transient brachial plexus injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admissions. C1 [Ohno, Mika S.; Cheng, Yvonne W.] Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Sparks, Teresa N.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. RP Ohno, MS (reprint author), Univ Calif San Francisco, Sch Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. OI Sparks, Teresa/0000-0002-8593-2186 FU NICHD NIH HHS [K12 HD001262] NR 30 TC 2 Z9 2 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2011 VL 205 IS 3 AR 282.e1 DI 10.1016/j.ajog.2011.06.051 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 812YF UT WOS:000294330000059 PM 22071065 ER PT J AU Paris, AE Greenberg, JA Ecker, JL McElrath, TF AF Paris, Amy E. Greenberg, James A. Ecker, Jeffrey L. McElrath, Thomas F. TI Is an episiotomy necessary with a shoulder dystocia? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 58th Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY MAY 15-19, 2010 CL San Francisco, CA SP Amer Coll Obstet & Gynecologists DE brachial plexus injury; episiotomy; shoulder dystocia ID MANAGEMENT; MANEUVERS AB OBJECTIVE: The objective of the study was to determine whether a decrease in the use of episiotomy was associated with a change in the frequency of brachial plexus injury. STUDY DESIGN: All births at Brigham and Women's Hospital from Sept. 1, 1998, through Aug. 31, 2009, were reviewed. The total number of births, mode of delivery, shoulder dystocias, episiotomies with and without shoulder dystocias, and brachial plexus injuries were recorded. A nonparametric test of trend was performed. RESULTS: There were a total of 94,842 births, 953 shoulder dystocias, and 102 brachial plexus injuries. The rate of episiotomy with shoulder dystocia dropped from 40% in 1999 to 4% in 2009 (P = .005) with no change in the rate of brachial plexus injuries per 1000 vaginal births. CONCLUSION: Despite historical recommendations for an episiotomy to prevent brachial plexus injury when a shoulder dystocia is encountered, the trend we observed does not suggest benefit from this practice. C1 [Paris, Amy E.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [McElrath, Thomas F.] Brigham & Womens Hosp, Div Maternal Fetal Med, Boston, MA 02115 USA. [Greenberg, James A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ecker, Jeffrey L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Obstet Serv, Boston, MA USA. RP Paris, AE (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Massachusetts Gen Hosp, 75 Francis St, Boston, MA 02115 USA. EM aeparis@partners.org OI Paris, Amy/0000-0003-1233-2400 NR 13 TC 3 Z9 3 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2011 VL 205 IS 3 AR 217.e1 DI 10.1016/j.ajog.2011.04.006 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 812YF UT WOS:000294330000026 PM 21620364 ER PT J AU Comander, J Gardiner, M Loewenstein, J AF Comander, Jason Gardiner, Matthew Loewenstein, John TI High-Resolution Optical Coherence Tomography Findings in Solar Maculopathy and the Differential Diagnosis of Outer Retinal Holes SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID RETINOPATHY; MICROHOLES AB PURPOSE: To characterize the morphology of outer retinal holes caused by solar maculopathy, using spectral-domain optical coherence tomography (SD-OCT). DESIGN: This study is an observational case series. METHODS: The SD-OCT findings of 3 patients (6 eyes) with chronic solar maculopathy are presented. RESULTS: SD-OCT demonstrates a characteristic appearance of partial-thickness hole(s) in the outer retina at the fovea. In 3 of 6 eyes, there is 1 hole directly beneath the umbo. In the remaining 3 eyes, there are multifocal holes spread across the fovea. Holes in more restricted layers, as had been previously reported with time-domain OCT, were not seen. In addition, advanced visualization of SD-OCT data demonstrates a hyperreflective ring around the outer retinal hole. CONCLUSIONS: SD-OCT can be used diagnose solar maculopathy. In patients with central scotomas, characteristic outer retinal hole(s) without inner retinal cystic changes may prompt the clinician to uncover an undisclosed history of sungazing. Similar OCT findings can be caused by welder's maculopathy, tamoxifen retinopathy, juxtafoveal macular telangiectasia, foveolar vitreomacular traction, or, rarely, a closed macular hole, achromatopsia, alkyl nitrite abuse, acute retinal pigment epitheliitis, or Stargardt disease. (Am J Ophthalmol 2011;152:413-419. (C) 2011 by Elsevier Inc. All rights reserved.) C1 [Comander, Jason] Massachusetts Eye & Ear Infirm, Retina Dept, Boston, MA 02114 USA. RP Comander, J (reprint author), Massachusetts Eye & Ear Infirm, Retina Dept, 243 Charles St, Boston, MA 02114 USA. EM jason_comander@meei.harvard.edu OI Comander, Jason/0000-0002-4257-7145; Gardiner, Matthew/0000-0002-8864-2379 NR 34 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 2011 VL 152 IS 3 BP 413 EP 419 DI 10.1016/j.ajo.2011.02.012 PG 7 WC Ophthalmology SC Ophthalmology GA 815IS UT WOS:000294519900012 PM 21708377 ER PT J AU Chaudhury, A He, XD Goyal, RK AF Chaudhury, Arun He, Xue-Dao Goyal, Raj K. TI Myosin Va plays a key role in nitrergic neurotransmission by transporting nNOS alpha to enteric varicosity membrane SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE DBA mice; LC8; enteric nerves; nitrergic inhibitory junction potential; myosin Va; active nNOS; inactive nNOS ID NITRIC-OXIDE SYNTHASE; SPLICED EXON-B; LIGHT-CHAIN; MICE GUT; DYNEIN; PROTEIN; BINDING; DIMERIZATION; TAIL; GENE AB Nitrergic neurotransmission at the smooth muscle neuromuscular junctions requires nitric oxide (NO) release that is dependent on the transport and docking of neuronal NO synthase (nNOS) alpha to the membrane of nerve terminals. However, the mechanism of translocation of nNOS alpha in actin-rich varicosities is unknown. We report here that the processive motor protein myosin Va is necessary for nitrergic neurotransmission. In wild-type mice, nNOS alpha-stained enteric varicosities colocalized with myosin Va and its tail constituent light chain 8 (LC8). In situ proximity ligation assay showed close association among nNOS alpha, myosin Va, and LC8. nNOS alpha was associated with varicosity membrane. Varicosities showed nitric oxide production upon stimulation with KCl. Intracellular microelectrode studies showed nitrergic IJP and smooth muscle hyperpolarizing responses to NO donor diethylenetriamine-NO (DNO). In contrast, enteric varicosities from myosin Va-deficient DBA (for dilute, brown, non-agouti) mice showed near absence of myosin Va but normal nNOS alpha and LC8. Membrane-bound nNOS alpha was not detectable, and the varicosities showed reduced NO production. Intracellular recordings in DBA mice showed reduced nitrergic IJPs but normal hyperpolarizing response to DNO. The nitrergic slow IJP was 9.1 +/- 0.7 mV in the wild-type controls and 3.4 +/- 0.3 mV in the DBA mice (P < 0.0001). Deficiency of myosin Va resulted in loss of nitrergic neuromuscular neurotransmission despite normal presence of nNOS alpha in the varicosities. These studies reveal the critical importance of myosin Va in nitrergic neurotransmission by facilitating transport of nNOS alpha to the varicosity membrane. C1 VA Boston HealthCare Syst, Ctr Swallowing & Motil Disorders, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goyal, RK (reprint author), VA Med Ctr, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM raj_goyal@hms.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-062867] FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-062867. NR 40 TC 7 Z9 7 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP PY 2011 VL 301 IS 3 BP G498 EP G507 DI 10.1152/ajpgi.00164.2011 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 812XW UT WOS:000294328200009 PM 21680773 ER PT J AU Harris, BS Zhang, YH Card, L Rivera, LB Brekken, RA Bradshaw, AD AF Harris, Brett S. Zhang, Yuhua Card, Lauren Rivera, Lee B. Brekken, Rolf A. Bradshaw, Amy D. TI SPARC regulates collagen interaction with cardiac fibroblast cell surfaces SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE extracellular matrix; fibrosis; matricellular; osteonectin; secreted protein acidic and rich in cysteine ID DIASTOLIC FUNCTION ROLE; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; FIBRILLAR COLLAGENS; PRESSURE-OVERLOAD; CYSTEINE SPARC; HEART-FAILURE; HYPERTROPHY; PROTEIN; DEGRADATION AB Harris BS, Zhang Y, Card L, Rivera LB, Brekken RA, Bradshaw AD. SPARC regulates collagen interaction with cardiac fibroblast cell surfaces. Am J Physiol Heart Circ Physiol 301: H841-H847, 2011. First published June 10, 2011; doi:10.1152/ajpheart.01247.2010.-Cardiac tissue from mice that do not express secreted protein acidic and rich in cysteine (SPARC) have reduced amounts of insoluble collagen content at baseline and in response to pressure overload hypertrophy compared with wild-type (WT) mice. However, the cellular mechanism by which SPARC affects myocardial collagen is not clearly defined. Although expression of SPARC by cardiac myocytes has been detected in vitro, immunohistochemistry of hearts demonstrated SPARC staining primarily associated with interstitial fibroblastic cells. Primary cardiac fibroblasts isolated from SPARC-null and WT mice were assayed for collagen I synthesis by [(3)H] proline incorporation into procollagen and by immunoblot analysis of procollagen processing. Bacterial collagenase was used to discern intracellular from extracellular forms of collagen I. Increased amounts of collagen I were found associated with SPARC-null versus WT cells, and the proportion of total collagen I detected on SPARC-null fibroblasts without propeptides [collagen-alpha(1)(I)] was higher than in WT cells. In addition, the amount of total collagen sensitive to collagenase digestion (extracellular) was greater in SPARC-null cells than in WT cells, indicating an increase in cell surface-associated collagen in the absence of SPARC. Furthermore, higher levels of collagen type V, a fibrillar collagen implicated in collagen fibril initiation, were found in SPARC-null fibroblasts. The absence of SPARC did not result in significant differences in proliferation or in decreased production of procollagen I by cardiac fibroblasts. We conclude that SPARC regulates collagen in the heart by modulating procollagen processing and interactions with fibroblast cell surfaces. These results are consistent with decreased levels of interstitial collagen in the hearts of SPARC-null mice being due primarily to inefficient collagen deposition into the extracellular matrix rather than to differences in collagen production. C1 [Zhang, Yuhua; Card, Lauren; Bradshaw, Amy D.] Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. [Harris, Brett S.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Harris, Brett S.] Ralph H Johnson Dept Vet Affairs Hlth Ctr, Charleston, SC USA. [Rivera, Lee B.; Brekken, Rolf A.] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dept Surg, Dallas, TX 75390 USA. RP Bradshaw, AD (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, 114 Doughty St,Rm 223 Gazes Strom Thurmond Res Bl, Charleston, SC 29425 USA. EM bradshad@musc.edu FU National Institutes of Health [P20-RR-16434-10, R01-CA-118240, P20-RR-017696, HL-094517]; Veterans Administration Merit Award FX This work was supported by National Institutes of Health Grants P20-RR-16434-10 (to B. S. Harris), R01-CA-118240 (to R. A. Brekken), P20-RR-017696 (to A. D. Bradshaw), and HL-094517 (to A. D. Bradshaw) and by Veterans Administration Merit Award (to A. D. Bradshaw). NR 33 TC 24 Z9 25 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2011 VL 301 IS 3 BP H841 EP H847 DI 10.1152/ajpheart.01247.2010 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 814EX UT WOS:000294431400025 PM 21666116 ER PT J AU Greenwood, TA Lazzeroni, LC Murray, SS Cadenhead, KS Calkins, ME Dobie, DJ Green, MF Gur, RE Gur, RC Hardiman, G Kelsoe, JR Leonard, S Light, GA Nuechterlein, KH Olincy, A Radant, AD Schork, NJ Seidman, LJ Siever, LJ Silverman, JM Stone, WS Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Freedman, R Braff, DL AF Greenwood, Tiffany A. Lazzeroni, Laura C. Murray, Sarah S. Cadenhead, Kristin S. Calkins, Monica E. Dobie, Dorcas J. Green, Michael F. Gur, Raquel E. Gur, Ruben C. Hardiman, Gary Kelsoe, John R. Leonard, Sherry Light, Gregory A. Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Schork, Nicholas J. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Freedman, Robert Braff, David L. TI Analysis of 94 Candidate Genes and 12 Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID 2 INDEPENDENT SAMPLES; CHILDHOOD-ONSET SCHIZOPHRENIA; NMDA-RECEPTOR SUBUNIT; HIGH-DENSITY FAMILIES; AMINO-ACID OXIDASE; SIB-PAIR FAMILIES; BIPOLAR DISORDER; PREPULSE INHIBITION; SUSCEPTIBILITY GENE; CHINESE POPULATION AB Objective: The authors used a custom array of 1,536 single-nucleotide polymorphisms (SNPs) to interrogate 94 functionally relevant candidate genes for schizophrenia and identify associations with 12 heritable neurophysiological and neurocognitive endophenotypes in data collected by the Consortium on the Genetics of Schizophrenia. Method: Variance-component association analyses of 534 genotyped subjects from 130 families were conducted by using Merlin software. A novel bootstrap total significance test was also developed to overcome the limitations of existing genomic multiple testing methods and robustly demonstrate significant associations in the context of complex family data and possible population stratification effects. Results: Associations with endophenotypes were observed for 46 genes of potential functional significance, with three SNPs at p < 10(-4), 27 SNPs at p < 10(-3), and 147 SNPs at p < 0.01. The bootstrap analyses confirmed that the 47 SNP-endophenotype combinations with the strongest evidence of association significantly exceeded that expected by chance alone, with 93% of these findings expected to be true. Many of the genes interact on a molecular level, and eight genes (e.g., NRG1 and ERBB4) displayed evidence for pleiotropy, revealing associations with four or more endophenotypes. The results collectively support a strong role for genes related to glutamate signaling in mediating schizophrenia susceptibility. Conclusions: This study supports use of relevant endophenotypes and the bootstrap total significance test for identifying genetic variation underlying the etiology of schizophrenia. In addition, the observation of extensive pleiotropy for some genes and singular associations for others suggests alternative, independent pathways mediating pathogenesis in the "group of schizophrenias." C1 [Braff, David L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Biomed Genom Lab, La Jolla, CA 92093 USA. San Diego VA Healthcare Syst, La Jolla, CA USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Beth Israel Deaconess Med Ctr, Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. James J Peters VA Med Ctr, New York, NY USA. RP Braff, DL (reprint author), Univ Calif San Diego, Dept Psychiat, Mail Code 0804,9500 Gilman Dr, La Jolla, CA 92093 USA. EM dbraff@ucsd.edu RI Greenwood, Tiffany/F-6356-2012; Tsuang, Debby/L-7234-2016; OI Greenwood, Tiffany/0000-0002-6080-6503; Tsuang, Debby/0000-0002-4716-1894; Lazzeroni, Laura/0000-0002-1846-6920 FU AstraZeneca; Merck; Pfizer; Ortho-McNeil Janssen Scientific Affairs; NIMH [R01-MH-065571, R01-MH-065588, R01-MH-065562, R01-MH-065707, R01-MH-065554, R01-MH-065578, R01-MH-065558, R01-MH-86135, P50-MH-086383, K01-MH-087889]; National Institute of Diabetes and Digestive and Kidney Diseases [DK-063491]; Department of Veterans Affairs, Veterans Integrated Service Network (VISN) 22; Mental Illness Research, Education, and Clinical Center; VA [478]; Department of Veterans Affairs VISN-21 Mental Illness Research, Education, and Clinical Center FX Dr. Greenwood has received unrelated support for consulting services from INFOTECH Soft. Dr. Freedman has a patent through the VA on DNA sequences in CHRNA7. Dr. Green has been a consultant for Abbott, Cypress, Dainippon Sumitomo, Lundbeck, Otsuka, Sanofi-Aventis, Takeda, and Teva, and he has been a speaker for Janssen Cilag, Otsuka, and Sunovion. Dr. Raquel Gur has received unrelated research support from AstraZeneca and Pfizer. Dr. Ruben Gur is a consultant to Johnson and Johnson and has received investigator-initiated grants from AstraZeneca, Merck, and Pfizer. Dr. Kelsoe is a consultant for AstraZeneca and Psynomics and is on a speakers bureau for Merck. Dr. Light has received unrelated support for consulting services from Allergan, Memory, and Roche. Dr. Nuechterlein reports an investigator-initiated research grant from Ortho-McNeil Janssen Scientific Affairs and consultation to Merck and Wyeth. Dr. Olincy has received unrelated research support from Lundbeck. Dr. Turetsky has received unrelated research support from AstraZeneca and Pfizer and is a consultant to Roche. The other authors report no financial relationships with commercial interests.; This study was supported by NIMH grants R01-MH-065571, R01-MH-065588, R01-MH-065562, R01-MH-065707, R01-MH-065554, R01-MH-065578, R01-MH-065558, R01-MH-86135, P50-MH-086383 (Dr. Freedman), and K01-MH-087889 (Dr. Greenwood); by grant DK-063491 from the National Institute of Diabetes and Digestive and Kidney Diseases (Dr. Hardiman); by the Department of Veterans Affairs, Veterans Integrated Service Network (VISN) 22, Mental Illness Research, Education, and Clinical Center (Dr. Braff); by a NARSAD Distinguished Investigator Award (Dr. Braff); and by additional salary support of Dr. Lazzeroni from VA Cooperative Studies Program study 478 and the Department of Veterans Affairs VISN-21 Mental Illness Research, Education, and Clinical Center. NR 134 TC 133 Z9 135 U1 2 U2 15 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 SEP PY 2011 VL 168 IS 9 BP 930 EP 946 DI 10.1176/appi.ajp.2011.10050723 PG 17 WC Psychiatry SC Psychiatry GA 814VA UT WOS:000294484100013 PM 21498463 ER PT J AU Shin, LM Bush, G Milad, MR Lasko, NB Brohawn, KH Hughes, KC Macklin, ML Gold, AL Karpf, RD Orr, SP Rauch, SL Pitman, RK AF Shin, Lisa M. Bush, George Milad, Mohammed R. Lasko, Natasha B. Brohawn, Kathryn Handwerger Hughes, Katherine C. Macklin, Michael L. Gold, Andrea L. Karpf, Rachel D. Orr, Scott P. Rauch, Scott L. Pitman, Roger K. TI Exaggerated Activation of Dorsal Anterior Cingulate Cortex During Cognitive Interference: A Monozygotic Twin Study of Posttraumatic Stress Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MEDIAL PREFRONTAL CORTEX; CORTICOLIMBIC BLOOD-FLOW; SCRIPT-DRIVEN IMAGERY; VIETNAM VETERANS; COMBAT EXPOSURE; DECISION-MAKING; COUNTING STROOP; NEURAL-NETWORKS; FUNCTIONAL MRI; ATTENTION AB Objective: Neuroimaging studies have revealed functional abnormalities in the anterior cingulate cortex in posttraumatic stress disorder (PTSD). The goal of this study was to determine whether hyperresponsivity of the dorsal anterior cingulate in PTSD is an acquired characteristic or a familial risk factor. Method: Using a case-control twin design, the authors studied combat-exposed veterans with PTSD (N=12) and their identical combat-unexposed co-twins (N=12), as well as combat-exposed veterans without PTSD (N=14) and their identical combat-unexposed co-twins (N=14). Participants underwent functional MRI during completion of the Multi-Source Interference Task, which reliably activates the dorsal anterior cingulate. Results: Combat-exposed veterans with PTSD and their unexposed co-twins had significantly greater activation in the dorsal anterior cingulate and tended to have larger response time difference scores, as compared to combat-exposed veterans without PTSD and their co-twins. Dorsal anterior cingulate activation in the exposed twins was positively correlated with their PTSD symptom severity. Dorsal anterior cingulate activation in the unexposed twins was positively correlated with their combat-exposed co-twins' PTSD symptom severity, but not with depression or alcohol use severity in the combat-exposed co-twins. Conclusions: Hyperresponsivity in the dorsal anterior cingulate appears to be a familial risk factor for the development of PTSD following psychological trauma. C1 [Shin, Lisa M.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. VA Res Serv, Manchester, NH USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. RP Shin, LM (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02155 USA. EM lisa.shin@tufts.edu RI Schueter, nicos/A-3625-2014; OI Gold, Andrea/0000-0003-4447-776X FU Benson-Henry Institute for Mind-Body Medicine; Center for Functional Neuroimaging Technologies [P41RR14075]; Centers for Disease Control and Prevention; David Judah Fund; Eli Lilly; Johnson & Johnson Center for the Study of Psychopathology; McIngvale Fund; McNeil; Mental Illness and Neuroscience Discovery (MIND) Institute; NARSAD; National Science Foundation; NIMH; Pfizer; U.S. Public Health Service [R01MH54636]; Department of Veterans Affairs; Department of Defense; National Personnel Records Center; Internal Revenue Service; NIH; National Opinion Research Center; National Research Council; National Academy of Sciences; Institute for Survey Research, Temple University; National Archives and Records Administration FX Dr. Bush has received research support from the Benson-Henry Institute for Mind-Body Medicine, the Center for Functional Neuroimaging Technologies (P41RR14075), the Centers for Disease Control and Prevention, the David Judah Fund, Eli Lilly, the Johnson & Johnson Center for the Study of Psychopathology, the McIngvale Fund, McNeil, the Mental Illness and Neuroscience Discovery (MIND) Institute, NARSAD, the National Science Foundation, NIMH, and Pfizer; he has also served as a consultant or speaker for Eli Lilly, Janssen, Johnson & Johnson, McNeil, Novartis, and Shire and received an honorarium for serving as a judge for an Intel Corporation science competition. All other authors report no financial relationships with commercial interests.; Supported by U.S. Public Health Service grant R01MH54636 to Dr. Pitman. The Department of Veterans Affairs provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry, and the VET Registry is also supported by the Department of Defense; the National Personnel Records Center, National Archives and Records Administration; the Internal Revenue Service; NIH; the National Opinion Research Center; the National Research Council, National Academy of Sciences; and the Institute for Survey Research, Temple University. NR 48 TC 71 Z9 72 U1 4 U2 15 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 SEP PY 2011 VL 168 IS 9 BP 979 EP 985 DI 10.1176/appi.ajp.2011.09121812 PG 7 WC Psychiatry SC Psychiatry GA 814VA UT WOS:000294484100017 PM 21724666 ER PT J AU Matthay, MA Brower, RG Carson, S Douglas, IS Eisner, M Hite, D Holets, S Kallet, RH Liu, KD MacIntyre, N Moss, M Schoenfeld, D Steingrub, J Thompson, BT Hudson, L Hough, C Neff, M Sims, K Watkins, T Steingrub, J Tidswell, M DeSouza, L Kardos, C Kozikowski, L Kozikowski, K Guntupalli, K Bandi, V Pope, C Brower, R Fessler, H Hager, D Mendez-Tellez, P Oakjones, K Needham, D Sevransky, J Workneh, A Han, S Murray, S Shanholtz, C Netzer, G Rock, P Sampaio, A Titus, J Harrington, T Herr, D Lee, B Bolouri, N Wiedemann, HP Ashton, RW Culver, DA Frederick, T Komara, JJ Guzman, JA Reddy, AJ Hejal, R Andrews, M Haney, D Lasalvia, S Thornton, JD Warren, EL Moss, M Benson, A Burnham, E Clark, B Gray, L Higgins, C Maloney, BJ Mealer, M Frankel, S Bost, T Dennen, P Hodgin, K Douglas, I Overdier, K Thompson, K Wolken, R MacIntyre, N Brown, L Cox, C Gentile, M Govert, J Knudsen, N Carson, S Chang, L Lanier, J Wheeler, AP Bernard, GR Hays, M Mogan, S Rice, T Hite, RD Morris, PE Howard, A Harvey, A Bender, K Wright, P Gross, S McLean, J Overton, A Truwit, J Enfield, K Marshall, M Clemmer, T Weaver, L Zenger, M Krueger, J Morris, A Ahmed, A Austin, A Dean, N Grissom, C Hirshberg, E Kumar, N Miller, R Napoli, L Orme, J Pandita, S Schreiber, G Struck, L Thomas, F Thomsen, G Lawton, C Leung, F Kim, P Fujii, T Baughman, J Kerwin, B Hanselman, D Sundar, K Alward, W Hill, T Campbell, E Ludwig, K Nielsen, D Pearce, M Matthay, MA Calfee, C Daniel, B Eisner, M Garcia, O Johnson, E Kallet, R Kordesch, K Liu, K Zhou, H Peterson, MW Blaauw, J Albertson, T Vlastelin, E Hubmayr, R Brown, D Gajic, O Hinds, R Holets, S Kor, DJ Passe, M Deboisblanc, B Lauto, P Romaine, C Meyaski, G Hunt, J Marr, A Long, EK Brierre, S LeBlanc, C Taylor, D Jain, S Seoane, L Simeone, F Fearon, J Duchesne, J Schoenfeld, D Aquino, M Dorer, D Guha, M Hammond, E Lavery, N Lazar, P Molina, I Morse, R Oldmixon, C Rawal, B Ringwood, N Shui, A Smoot, E Thompson, BT Harabin, A Bredow, S Waclawiw, M Weinmann, G Spragg, RG Slutsky, A Levy, M Markovitz, B Petkova, E Weijer, C Sznajder, J Begg, M Israel, E Lewis, J Parsons, P AF Matthay, Michael A. Brower, Roy G. Carson, Shannon Douglas, Ivor S. Eisner, Mark Hite, Duncan Holets, Steven Kallet, Richard H. Liu, Kathleen D. MacIntyre, Neil Moss, Marc Schoenfeld, David Steingrub, Jay Thompson, B. Taylor Hudson, L. Hough, C. Neff, M. Sims, K. Watkins, T. Steingrub, J. Tidswell, M. DeSouza, L. Kardos, C. Kozikowski, L. Kozikowski, K. Guntupalli, K. Bandi, V. Pope, C. Brower, R. Fessler, H. Hager, D. Mendez-Tellez, P. Oakjones, K. Needham, D. Sevransky, J. Workneh, A. Han, S. Murray, S. Shanholtz, C. Netzer, G. Rock, P. Sampaio, A. Titus, J. Harrington, T. Herr, D. Lee, B. Bolouri, N. Wiedemann, H. P. Ashton, R. W. Culver, D. A. Frederick, T. Komara, J. J. Guzman, J. A. Reddy, A. J. Hejal, R. Andrews, M. Haney, D. Lasalvia, S. Thornton, J. D. Warren, E. L. Moss, M. Benson, A. Burnham, E. Clark, B. Gray, L. Higgins, C. Maloney, B. J. Mealer, M. Frankel, S. Bost, T. Dennen, P. Hodgin, K. Douglas, I. Overdier, K. Thompson, K. Wolken, R. MacIntyre, N. Brown, L. Cox, C. Gentile, M. Govert, J. Knudsen, N. Carson, S. Chang, L. Lanier, J. Wheeler, A. P. Bernard, G. R. Hays, M. Mogan, S. Rice, T. Hite, R. D. Morris, P. E. Howard, A. Harvey, A. Bender, K. Wright, P. Gross, S. McLean, J. Overton, A. Truwit, J. Enfield, K. Marshall, M. Clemmer, T. Weaver, L. Zenger, M. Krueger, J. Morris, A. Ahmed, A. Austin, A. Dean, N. Grissom, C. Hirshberg, E. Kumar, N. Miller, R. Napoli, L. Orme, J. Pandita, S. Schreiber, G. Struck, L. Thomas, F. Thomsen, G. Lawton, C. Leung, F. Kim, P. Fujii, T. Baughman, J. Kerwin, B. Hanselman, D. Sundar, K. Alward, W. Hill, T. Campbell, E. Ludwig, K. Nielsen, D. Pearce, M. Matthay, M. A. Calfee, C. Daniel, B. Eisner, M. Garcia, O. Johnson, E. Kallet, R. Kordesch, K. Liu, K. Zhou, H. Peterson, M. W. Blaauw, J. Albertson, T. Vlastelin, E. Hubmayr, R. Brown, D. Gajic, O. Hinds, R. Holets, S. Kor, D. J. Passe, M. Deboisblanc, B. Lauto, P. Romaine, C. Meyaski, G. Hunt, J. Marr, A. Long, Earl K. Brierre, S. LeBlanc, C. Taylor, D. Jain, S. Seoane, L. Simeone, F. Fearon, J. Duchesne, J. Schoenfeld, D. Aquino, M. Dorer, D. Guha, M. Hammond, E. Lavery, N. Lazar, P. Molina, I. Morse, R. Oldmixon, C. Rawal, B. Ringwood, N. Shui, A. Smoot, E. Thompson, B. T. Harabin, A. Bredow, S. Waclawiw, M. Weinmann, G. Spragg, R. G. Slutsky, A. Levy, M. Markovitz, B. Petkova, E. Weijer, C. Sznajder, J. Begg, M. Israel, E. Lewis, J. Parsons, P. CA Natl Heart Lung Blood Inst TI Randomized, Placebo-controlled Clinical Trial of an Aerosolized beta(2)-Agonist for Treatment of Acute Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE pulmonary edema; acute respiratory distress syndrome; alveolar epithelium ID RESPIRATORY-DISTRESS-SYNDROME; ALVEOLAR FLUID CLEARANCE; PULMONARY-EDEMA FLUID; BETA(2)-ADRENERGIC RECEPTOR; EPITHELIAL TRANSPORT; DECREASES EXPRESSION; VENTILATED PATIENTS; RAT LUNGS; PROGRESS; CELLS AB Rationale: beta(2)-Adrenergic receptor agonists accelerate resolution of pulmonary edema in experimental and clinical studies. Objectives: This clinical trial was designed to test the hypothesis that an aerosolized beta(2)-agonist, albuterol, would improve clinical outcomes in patients with acute lung injury (ALI). Methods: We conducted a multicenter, randomized, placebo-controlled clinical trial in which 282 patients with ALI receiving mechanical ventilation were randomized to receive aerosolized albuterol (5 mg) or saline placebo every 4 hours for up to 10 days. The primary outcome variable for the trial was ventilator-free days. Measurements and Main Results: Ventilator-free days were not significantly different between the albuterol and placebo groups (means of 14.4 and 16.6 d, respectively; 95% confidence interval for the difference, -4.7 to 0.3 d; P = 0.087). Rates of death before hospital discharge were not significantly different between the albuterol and placebo groups (23.0 and 17.7%, respectively; 95% confidence interval for thedifference, -4.0 to 14.7%; P = 0.30). In the subset of patients with shock before randomization, the number of ventilator-free days was lower with albuterol, although mortality was not different. Overall, heart rates were significantly higher in the albuterol group by approximately 4 beats/minute in the first 2 days after randomization, but rates of new atrial fibrillation (10% in both groups) and other cardiac dysrhythmias were not significantly different. Conclusions: These results suggest that aerosolized albuterol does not improve clinical outcomes in patients with ALI. Routine use of beta(2)-agonist therapy in mechanically ventilated patients with ALI cannot be recommended. C1 [Matthay, Michael A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Brower, Roy G.] Johns Hopkins Univ, Baltimore, MD USA. [Carson, Shannon; Douglas, Ivor S.; Hite, Duncan; Carson, S.; Chang, L.; Lanier, J.] Univ N Carolina, Chapel Hill, NC USA. [Eisner, Mark] Genentech Inc, San Francisco, CA USA. [Holets, Steven] Mayo Clin, Rochester, MN USA. [Kallet, Richard H.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [MacIntyre, Neil; MacIntyre, N.; Brown, L.; Cox, C.; Gentile, M.; Govert, J.; Knudsen, N.] Duke Univ, Durham, NC USA. [Moss, Marc] Univ Colorado, Denver, CO 80202 USA. [Schoenfeld, David; Thompson, B. Taylor] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Steingrub, Jay; Steingrub, J.; Tidswell, M.; DeSouza, L.; Kardos, C.; Kozikowski, L.; Kozikowski, K.] Baystate Med Ctr, Springfield, MA USA. [Hudson, L.; Hough, C.; Neff, M.; Sims, K.; Watkins, T.] Univ Washington, Harborview, WA USA. [Guntupalli, K.; Bandi, V.; Pope, C.] Baylor Coll Med, Houston, TX 77030 USA. [Brower, R.; Fessler, H.; Hager, D.; Mendez-Tellez, P.; Oakjones, K.; Needham, D.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Shanholtz, C.; Netzer, G.; Rock, P.; Sampaio, A.; Titus, J.; Harrington, T.] Univ Maryland, College Pk, MD 20742 USA. [Herr, D.; Lee, B.; Bolouri, N.] Washington Hosp Ctr, Washington, DC USA. [Wiedemann, H. P.; Ashton, R. W.; Culver, D. A.; Frederick, T.; Komara, J. J.; Guzman, J. A.; Reddy, A. J.] Cleveland Clin Fdn, Cleveland, OH USA. [Hejal, R.; Andrews, M.; Haney, D.] Univ Hosp Cleveland, Cleveland, OH 44106 USA. [Douglas, I.; Overdier, K.; Thompson, K.; Wolken, R.] Denver Hlth Med Ctr, Denver, CO USA. [Wheeler, A. P.; Bernard, G. R.; Hays, M.; Mogan, S.; Rice, T.] Vanderbilt Univ, Nashville, TN USA. [Hite, R. D.; Morris, P. E.; Howard, A.; Harvey, A.; Bender, K.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Truwit, J.; Enfield, K.; Marshall, M.] Univ Virginia, Charlottesville, VA 22903 USA. [Peterson, M. W.; Blaauw, J.] Univ Calif San Francisco, Fresno, CA USA. [Albertson, T.; Vlastelin, E.] Univ Calif Davis, Davis, CA USA. [Deboisblanc, B.; Lauto, P.; Romaine, C.; Meyaski, G.; Hunt, J.; Marr, A.; Long, Earl K.] Louisiana State Univ, Baton Rouge, LA 70803 USA. [Brierre, S.; LeBlanc, C.] Baton Rouge Gen Med Ctr Mid City, Baton Rouge, LA USA. [Brierre, S.; LeBlanc, C.] Baton Rouge Gen Med Ctr Bluebonnet, Baton Rouge, LA USA. [Simeone, F.; Fearon, J.; Duchesne, J.] Tulane Univ, New Orleans, LA 70118 USA. [Schoenfeld, D.; Aquino, M.; Dorer, D.; Guha, M.; Hammond, E.; Lavery, N.; Lazar, P.; Molina, I.; Morse, R.; Oldmixon, C.; Rawal, B.; Ringwood, N.; Shui, A.; Smoot, E.; Thompson, B. T.] Massachusetts Gen Hosp, Clin Coordinating Ctr, Boston, MA 02114 USA. [Schoenfeld, D.; Aquino, M.; Dorer, D.; Guha, M.; Hammond, E.; Lavery, N.; Lazar, P.; Molina, I.; Morse, R.; Oldmixon, C.; Rawal, B.; Ringwood, N.; Shui, A.; Smoot, E.; Thompson, B. T.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Matthay, MA (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, 505 Parnassus Ave,M-917, San Francisco, CA 94143 USA. EM michael.matthay@ucsf.edu RI Seoane, Leonardo/A-6069-2011 OI Seoane, Leonardo/0000-0001-9262-6673 FU National Heart, Lung, and Blood Institute [NO1-HR-56165-56713]; AstraZeneca (AZ); Asthmatx; CareFusion; Phillips Healthcare; Covidien Healthcare; Abbott; CMIC; American Society of Nephrologists; Averion International; Mylan; Posen; Lilly FX Supported by National Heart, Lung, and Blood Institute contracts NO1-HR-56165-56713.; M. A. M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R. G. B. has received fees for board activities from AstraZeneca (AZ). S. C. has received consultancy fees from Asthmatx. I. S. D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M. E. is an employee of Genentech. R. D. H. holds stock in Discovery Laboratories, Inc. S. H. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R. H. K. has received fees for board activities from CareFusion, and consultancy fees from Phillips Healthcare and Covidien Healthcare. K. D. L. has not received funding from Abbott and CMIC; however, she has received donated reagents from them; she holds stock in Amgen; she has received lecture fees from the American Society of Nephrologists, and has been employed by the American Society of Nephrologists as an associate editor for NephSAP. NM has received consultancy fees from CareFusion. M. M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. D. S. has received consultancy fees from Averion International, Mylan, and Posen; he holds stock in Averion International. J.S. does not have a financial relationship with a commercial entity that has an interest in subject of this manuscript. B. T. T. has received consultancy fees from Lilly and AZ. NR 40 TC 152 Z9 159 U1 0 U2 13 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2011 VL 184 IS 5 BP 561 EP 568 DI 10.1164/rccm.201012-2090OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 814ST UT WOS:000294478200016 ER PT J AU Linas, BP Wong, AY Freedberg, KA Horsburgh, CR AF Linas, Benjamin P. Wong, Angela Y. Freedberg, Kenneth A. Horsburgh, C. Robert, Jr. TI Priorities for Screening and Treatment of Latent Tuberculosis Infection in the United States SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE latent tuberculosis; cost-effectiveness; tuberculin skin test; interferon-gamma release assay ID ISONIAZID PREVENTIVE THERAPY; COST-EFFECTIVENESS ANALYSIS; GAMMA RELEASE ASSAYS; HIGH-INCOME COUNTRIES; FOREIGN-BORN PERSONS; INJECTION-DRUG USERS; QUANTIFERON(R)-TB GOLD; PULMONARY TUBERCULOSIS; RHEUMATOID-ARTHRITIS; ACTIVE TUBERCULOSIS AB Rationale: To improve the effectiveness of tuberculosis (TB) control programs in the United States by identifying cost-effective priorities for screening for latent tuberculosis infection (LTBI). Objectives: To estimate the cost-effectiveness of LTBI screening using the tuberculin skin test (TST) andinterferon-gamma release assays (IGRAs). Methods: A Markov model of screening for LTBI with TST and IGRA in risk-groups considered in current LTBI screening guidelines. Measurements and Main Results: In all risk-groups, TST and IGRA screening resulted in increased mean life expectancy, ranging from 0.03-0.24 life-months per person screened. IGRA screening resulted in greater life expectancy gains than TST. Screening always cost more than not screening, but IGRA was cost-saving compared with TST in some groups. Four patterns of cost-effectiveness emerged, related to four risk categories. (1) Individuals at highest risk of TB reactivation (close contacts and those infected with HIV): the incremental cost-effectiveness ratio (ICER) of IGRA compared with TST was less than $100,000 per quality-adjusted life year (QALY) gained. (2) The foreign-born: IGRA was cost-saving compared with TST and cost-effective compared with no screening (ICER <$100,000 per QALY gained). (3) Vulnerable populations (e. g., homeless, drug user, or former prisoner): the ICER of TST screening was approximately $100,000-$150,000 per QALY gained, but IGRA was not cost-effective. (4) Medical comorbidities (e. g., diabetes): the ICER of screening with TST or IGRA was greater than $100,000 per QALY. Conclusions: LTBI screening guidelines could make progress toward TB elimination by prioritizing screening for close contacts, those infected with HIV, and the foreign-born regardless of time living in the United States. For these groups, IGRA screening was more cost-effective than TST screening. C1 [Linas, Benjamin P.] Boston Med Ctr, HIV Epidemiol & Outcomes Res Unit, Infect Dis Sect, Evans Biomed Res Ctr, Boston, MA 02118 USA. [Linas, Benjamin P.; Freedberg, Kenneth A.; Horsburgh, C. Robert, Jr.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wong, Angela Y.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Wong, Angela Y.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Harvard Ctr AIDS Res CFAR, Boston, MA USA. RP Linas, BP (reprint author), Boston Med Ctr, HIV Epidemiol & Outcomes Res Unit, Infect Dis Sect, Evans Biomed Res Ctr, 650 Albany St,Rm 647, Boston, MA 02118 USA. EM benjamin.linas@bmc.org OI Horsburgh, C./0000-0001-6838-7895; Linas, Benjamin/0000-0001-9574-7075 FU National Institute of Allergy and Infectious Diseases [K01AI073193, K24AI062476, R37AI42006] FX Supported by the National Institute of Allergy and Infectious Diseases (K01AI073193, K24AI062476, and R37AI42006). NR 93 TC 65 Z9 65 U1 1 U2 11 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2011 VL 184 IS 5 BP 590 EP 601 DI 10.1164/rccm.201101-0181OC PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 814ST UT WOS:000294478200019 PM 21562129 ER PT J AU Chami, HA Baldwin, CM Silverman, A Zhang, Y Rapoport, DM Punjabi, N Gottlieb, DJ AF Chami, Hassan A. Baldwin, Carol M. Silverman, Angela Zhang, Ying Rapoport, David M. Punjabi, Naresh Gottlieb, Daniel J. TI Sleepiness, Quality of Life, and Sleep Maintenance in REM versus NREM Sleep-Disordered Breathing (vol 181, pg 997, 2010) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Correction C1 [Chami, Hassan A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Baldwin, Carol M.] VA Boston Hlth Care Syst, W Roxbury, MA USA. [Silverman, Angela] Arizona State Univ, Coll Nursing & Hlth Innovat, Phoenix, AZ USA. [Zhang, Ying] MedStar Res Inst, Hyattsville, MD USA. [Rapoport, David M.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Punjabi, Naresh] NYU, Sch Med, New York, NY USA. [Gottlieb, Daniel J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Chami, HA (reprint author), Boston Univ, Sch Med, Boston, MA 02118 USA. OI Chami, Hassan/0000-0002-9239-2528 NR 1 TC 1 Z9 1 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2011 VL 184 IS 5 BP 622 EP 622 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 814ST UT WOS:000294478200027 PM 21998855 ER PT J AU Johnson, DW Oren-Grinberg, A AF Johnson, Daniel W. Oren-Grinberg, Achikam TI Perioperative Point-of-Care Ultrasonography The Past and the Future Are in Anesthesiologists' Hands SO ANESTHESIOLOGY LA English DT Editorial Material ID CENTRAL VENOUS CANNULATION; BRACHIAL-PLEXUS BLOCK; TRAUMATIC PNEUMOTHORAX; BEDSIDE ULTRASOUND; CHEST RADIOGRAPHY; DIAGNOSIS C1 [Johnson, Daniel W.] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Oren-Grinberg, Achikam] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. RP Johnson, DW (reprint author), Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM dwjohnson@partners.org NR 25 TC 11 Z9 12 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2011 VL 115 IS 3 BP 460 EP 462 DI 10.1097/ALN.0b013e31822a62a1 PG 3 WC Anesthesiology SC Anesthesiology GA 811KD UT WOS:000294207400003 PM 21792050 ER PT J AU Feng, Y Zou, L Zhang, M Li, Y Chen, C Chao, W AF Feng, Yan Zou, Lin Zhang, Ming Li, Yan Chen, Chan Chao, Wei TI MyD88 and Trif Signaling Play Distinct Roles in Cardiac Dysfunction and Mortality during Endotoxin Shock and Polymicrobial Sepsis SO ANESTHESIOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; INNATE IMMUNITY; CECAL LIGATION; HOST-DEFENSE; NEUTROPHIL MIGRATION; SEPTIC PERITONITIS; MYOCARDIAL INJURY; LABORATORY MODELS; SURVIVAL; PUNCTURE AB Background: Toll-like receptors (TLRs) such as TLR2, TLR4, and TLR9 contribute to the pathogenesis of polymicrobial sepsis. These TLRs signal via the common myeloid differentiation factor 88 (MyD88)-dependent pathways. TLR4 also signals through MyD88-independent but TIR domain-containing adaptor inducing interferon-beta-mediated transcription factor (Trif)-dependent pathway. The role of the two signaling pathways in cardiac dysfunction during polymicrobial sepsis and endotoxin shock is unknown. Methods: Sepsis was generated by cecum ligation and puncture. Mice were divided into sham and cecum ligation and puncture groups or subjected to saline or endotoxin. Left ventricular function was assessed in a Langendorff apparatus or by echocardiography. Cytokines were examined using a multiplex immunoassay. Neutrophil migratory and phagocytic functions were assessed using flow cytometry. Results: In comparison with wild-type mice, MyD88(-/-) but not Trif(-/-) mice had markedly improved cardiac function and survival after cecum ligation and puncture. In comparison, both MyD88(-/-) and Trif(-/-) mice were protected from cardiac depression and mortality during endotoxin shock. Septic MyD88(-/-) but not Trif(-/-) mice had diminished cytokine production in serum and in peritoneal space in comparison with wild-type mice after cecum ligation and puncture. In contrast, both MyD88(-/-) and Trif(-/-) mice had attenuated serum cytokines in comparison with wildtype mice after endotoxin challenge. Neither MyD88 nor Trif signaling had any effect on neutrophil phagocytic function or bacterial clearance at 24 h of polymicrobial sepsis. Conclusions: These studies establish that MyD88 but not Trif signaling plays a critical role in mediating cardiac dysfunction, systemic inflammation, and mortality during polymicrobial sepsis. Both MyD88 and Trif are essential for cardiac depression and mortality during endotoxin shock. C1 [Feng, Yan; Zou, Lin; Zhang, Ming; Li, Yan; Chen, Chan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Chao, W (reprint author), Anesthesia Ctr Crit Care Res, 149 13th St,Room 4-212, Charlestown, MA 02129 USA. EM wchao@partners.org RI Feng, Yan/H-5808-2012 FU National Institutes of Health (Bethesda, Maryland) [GM-080906]; American Heart Association (Dallas, Texas) [0755890T] FX This work was supported by the National Institutes of Health grant GM-080906 (Bethesda, Maryland) and American Heart Association grant 0755890T (Dallas, Texas). Drs. Feng, Zou, and Zhang contributed equally to this work. NR 45 TC 20 Z9 21 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2011 VL 115 IS 3 BP 555 EP 567 DI 10.1097/ALN.0b013e31822a22f7 PG 13 WC Anesthesiology SC Anesthesiology GA 811KD UT WOS:000294207400015 PM 21792053 ER PT J AU Aebi, S Sun, Z Braun, D Price, KN Castiglione-Gertsch, M Rabaglio, M Gelber, RD Crivellari, D Lindtner, J Snyder, R Karlsson, P Simoncini, E Gusterson, BA Viale, G Regan, MM Coates, AS Goldhirsch, A AF Aebi, S. Sun, Z. Braun, D. Price, K. N. Castiglione-Gertsch, M. Rabaglio, M. Gelber, R. D. Crivellari, D. Lindtner, J. Snyder, R. Karlsson, P. Simoncini, E. Gusterson, B. A. Viale, G. Regan, M. M. Coates, A. S. Goldhirsch, A. TI Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: Long-term follow up on IBCSG Trial IX SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant chemotherapy; breast cancer; estrogen receptor; postmenopause; tamoxifen ID 2 RANDOMIZED-TRIALS; ADJUVANT CHEMOENDOCRINE THERAPY; BREAST-CANCER TRIALS; CLINICAL-TRIALS; PREDICTIVE-VALUE; CHEMOTHERAPY; EXPRESSION; ESTROGEN; CYCLOPHOSPHAMIDE; DOCETAXEL AB Background: The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)positive lymph node-negative breast cancer is being reassessed. Patients and methods: After stratification by ER status, 1669 postmenopausal patients with operable lymph nodenegative breast cancer were randomly assigned to three 28-day courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMF/tamoxifen) or to tamoxifen alone for 5 years. Results: ERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMF/tamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes. Conclusion: CMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy. C1 [Aebi, S.] Univ Hosp Bern, Div Med Oncol, CH-3010 Bern, Switzerland. [Aebi, S.] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Gelber, R. D.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst,Frontier Sci & Technol Res, IBCSG Stat Ctr,Dept Biostat & Computat Biol,Med S, Boston, MA 02115 USA. [Price, K. N.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Castiglione-Gertsch, M.] Univ Hosp Geneva, Dept Med, Med Oncogynecol Unit, Geneva, Switzerland. [Rabaglio, M.] IBCSG Coordinating Ctr, Bern, Switzerland. [Rabaglio, M.] Inselspital Bern, CH-3010 Bern, Switzerland. [Crivellari, D.] Ctr Riferimento Oncol, Dept Med Oncol, I-33081 Aviano, Italy. [Lindtner, J.] Inst Oncol, Dept Surg Oncol, Ljulbljana, Slovenia. [Snyder, R.] St Vincents Hosp, Dept Med Oncol, Melbourne, Vic, Australia. [Karlsson, P.] Univ Gothenburg, Inst Clin Sci, Dept Oncol, Sahlgrenska Acad,Sahlgrenska Univ Hosp, Gothenburg, Sweden. [Simoncini, E.] Spedali Civili Brescia, Dept Med Oncol, Brescia, Italy. [Gusterson, B. A.] Univ Glasgow, Inst Canc Sci, IBCSG Pathol Review Off, Glasgow, Lanark, Scotland. [Viale, G.] Univ Milan, IBCSG Pathol Off, European Inst Oncol, Div Pathol & Lab Med, Milan, Italy. [Coates, A. S.] Int Breast Canc Study Grp, Bern, Switzerland. [Coates, A. S.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Goldhirsch, A.] European Inst Oncol, Dept Med, Milan, Italy. [Goldhirsch, A.] Oncol Inst So Switzerland, Dept Med Oncol, Bellinzona, Switzerland. RP Aebi, S (reprint author), Luzerner Kantonsspital, Div Med Oncol, CH-6000 Luzern, Switzerland. EM stefan.aebi@onkologie.ch RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 FU Australian New Zealand Breast Cancer Trials Group [890028, 920876, 950328, 980379, 141711]; Cancer Association of South Africa; Foundation for Clinical Research of Eastern Switzerland (OSKK); Swedish Society for Cancer Research (Cancerfonden) FX We acknowledge the initial support provided by the Ludwig Institute for Cancer Research and the Cancer League of Ticino and the continuing support for central coordination, data management, and statistics provided by the Swedish Cancer Society; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (grant numbers 890028, 920876, 950328, 980379, 141711); the Frontier Science and Technology Research Foundation; the Swiss Group for Clinical Cancer Research (SAKK); the Swiss Cancer League; and the United States National Institutes of Health (CA-75362). We also acknowledge support for the Cape Town participants from the Cancer Association of South Africa; for the St. Gallen participants from the Foundation for Clinical Research of Eastern Switzerland (OSKK); and for the Gothenburg participants from the Swedish Society for Cancer Research (Cancerfonden). NR 24 TC 26 Z9 26 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 2011 VL 22 IS 9 BP 1981 EP 1987 DI 10.1093/annonc/mdq754 PG 7 WC Oncology SC Oncology GA 814ZE UT WOS:000294495100006 PM 21282282 ER PT J AU Stucky, CCH Pockaj, BA Novotny, PJ Sloan, JA Sargent, DJ O'Connell, MJ Beart, RW Skibber, JM Nelson, H Weeks, JC AF Stucky, Chee-Chee H. Pockaj, Barbara A. Novotny, Paul J. Sloan, Jeff A. Sargent, Daniel J. O'Connell, Michael J. Beart, Robert W. Skibber, John M. Nelson, Heidi Weeks, Jane C. TI Long-Term Follow-Up and Individual Item Analysis of Quality of Life Assessments Related to Laparoscopic-Assisted Colectomy in the COST Trial 93-46-53 (INT 0146) SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID INDEPENDENT PROGNOSTIC-FACTOR; RANDOMIZED CLINICAL-TRIAL; COLON-CANCER; COLORECTAL-CANCER; OPEN SURGERY; SURVIVAL; OUTCOMES; COMPLICATIONS; RESECTION; DISTRESS AB Postoperative outcomes of patients undergoing laparoscopic-assisted colectomy (LAC) have shown modest improvements in recovery but only minimal differences in quality of life (QOL) compared with open colectomy. We therefore sought to assess the effect of LAC on QOL in the short and long term, using individual item analysis of multi-item QOL assessments. QOL variables were analyzed in 449 randomized patients from the COST trial 93-46-53 (INT 0146). Both cross-sectional single-time and change from baseline assessments were run at day 2, week 2, month 2, and month 18 postoperatively in an intention-to-treat analysis using Wilcoxon rank-sum tests. Stepwise regression models were used to determine predictors of QOL. Of 449 colon cancer patients, 230 underwent LAC and 219 underwent open colectomy. Subdomain analysis revealed a clinically moderate improvement from baseline for LAC in total QOL index at 18 months (P = 0.02) as well as other small symptomatic improvements. Poor preoperative QOL as indicated by a rating scale of a parts per thousand currency sign 50 was an independent predictor of poor QOL at 2 months postoperatively. QOL variables related to survival were baseline support (P = 0.001) and baseline outlook (P = 0.01). Eighteen months after surgery, any differences in quality of life between patients randomized to LAC or open colectomy favored LAC. However, the magnitude of the benefits was small. Patients with poor preoperative QOL appear to be at higher risk for difficult postoperative courses, and may be candidates for enhanced ancillary services to address their particular needs. C1 [Stucky, Chee-Chee H.; Pockaj, Barbara A.] Mayo Clin Arizona, Dept Surg, Phoenix, AZ USA. [Novotny, Paul J.; Sloan, Jeff A.; Sargent, Daniel J.] Mayo Clin, Dept Biostat, Rochester, MN USA. [O'Connell, Michael J.] Natl Surg Adjuvant Breast & Bowel Project Operat, Pittsburgh, PA USA. [Beart, Robert W.] Univ So Calif, Keck Sch Med, Dept Surg, Los Angeles, CA 90033 USA. [Skibber, John M.] Univ Texas MD Anderson Canc Ctr, Dept Surg, Houston, TX 77030 USA. [Nelson, Heidi] Mayo Clin, Dept Surg, Rochester, MN USA. [Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Stucky, CCH (reprint author), Mayo Clin Arizona, Dept Surg, Phoenix, AZ USA. EM pockaj.barbara@mayo.edu OI Sargent, Daniel/0000-0002-2684-4741 FU National Cancer Institute; North Central Cancer Treatment Group FX Original funding of the Clinical Outcomes of Surgical Therapy trial 93-46-53 was provided by the National Cancer Institute in association with the North Central Cancer Treatment Group. NR 26 TC 28 Z9 30 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD SEP PY 2011 VL 18 IS 9 BP 2422 EP 2431 DI 10.1245/s10434-011-1650-2 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 813DJ UT WOS:000294346700006 PM 21452066 ER PT J AU Chitsaz, S Jaussaud, N Chau, E Yan, KS Azadani, AN Ratcliffe, MB Tseng, EE AF Chitsaz, Sam Jaussaud, Nicolas Chau, Edward Yan, Kimberly S. Azadani, Ali N. Ratcliffe, Mark B. Tseng, Elaine E. TI Operative Risks and Survival in Veterans With Severe Aortic Stenosis: Surgery Versus Medical Therapy SO ANNALS OF THORACIC SURGERY LA English DT Article ID VALVULAR HEART-DISEASE; VALVE-REPLACEMENT; ELDERLY-PATIENTS; NATURAL-HISTORY; INTERVENTIONS; IMPLANTATION; OUTCOMES AB Background. Transcatheter aortic valves were developed as an alternative to surgery for the one third to two thirds of patients with severe aortic stenosis who do not undergo aortic valve replacement. In this study, we examined reasons for medical management of aortic stenosis in relation to operative risks and outcomes for veterans with and without valve replacement. Methods. The echocardiography database was screened from 2000 to 2007 for severe aortic stenosis. The Society of Thoracic Surgeons risk scores and survival were determined for patients with and without aortic valve replacement. Results. Of 132 severe aortic stenosis patients included, 42% were medically managed. Predicted operative mortality risk was lower for surgical patients than for medical patients (4.5% +/- 4.2% versus 6.8% +/- 5.1%, p = 0.002). Overall, the most common reason for medical management of aortic stenosis was assumption that the patient was high risk for surgery (30.4%). The surgery group had significantly higher median survival (92.2 versus 32.4 months) and 5-year survival (71% versus 37%, p < 0.001) than the medical group. Cardiac surgery was not consulted in 61% of medically managed patients, of whom only 18% had Society of Thoracic Surgeons risk score of 10 or greater. Aortic valve replacement was an independent predictor of lower mortality (hazard ratio 0.43, p = 0.008). Conclusions. Although operative risk was higher among patients who did not undergo surgery, most were not the 10% or greater required for transcatheter valves. Given the significantly lower survival with medical therapy, aortic valve replacement should be carefully considered for most severe aortic stenosis patients whereas transcatheter aortic valves should be reserved for patients with high operative risks. (Ann Thorac Surg 2011;92:866-72) (C) 2011 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, Med Ctr, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Tseng, EE (reprint author), UCSF Med Ctr, 500 Parnassus Ave,Ste W405,Box 0118, San Francisco, CA 94143 USA. EM elaine.tseng@ucsfmedctr.org RI Chitsaz, Sam/C-4586-2008 FU American Heart Association; Northern California Institute for Research and Education; Federation Francaise de Cardiologie/Societe Francaise de Cardiologie; Societe Francaise de Chirurugie Thoracique et Cardio-Vasculaire FX This work was supported by the American Heart Association, the Northern California Institute for Research and Education, and the Federation Francaise de Cardiologie/Societe Francaise de Cardiologie, and Societe Francaise de Chirurugie Thoracique et Cardio-Vasculaire. NR 18 TC 3 Z9 3 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 SEP PY 2011 VL 92 IS 3 BP 866 EP 872 DI 10.1016/j.athoracsur.2011.04.028 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 811WJ UT WOS:000294247400024 PM 21871271 ER PT J AU Wenk, JF Eslami, P Zhang, ZH Xu, C Kuhl, E Gorman, JH Robb, JD Ratcliffe, MB Gorman, RC Guccione, JM AF Wenk, Jonathan F. Eslami, Parastou Zhang, Zhihong Xu, Chun Kuhl, Ellen Gorman, Joseph H., III Robb, J. Daniel Ratcliffe, Mark B. Gorman, Robert C. Guccione, Julius M. TI A Novel Method for Quantifying the In-Vivo Mechanical Effect of Material Injected Into a Myocardial Infarction SO ANNALS OF THORACIC SURGERY LA English DT Article ID LEFT-VENTRICULAR ANEURYSM; FINITE-ELEMENT MODEL; CANINE LEFT-VENTRICLE; STRESS-ANALYSIS; CONTRACTION; PATTERNS; STRAIN; MUSCLE; HEART AB Background. Infarcted regions of myocardium exhibit functional impairment ranging in severity from hypokinesis to dyskinesis. We sought to quantify the effects of injecting a calcium hydroxyapatite-based tissue filler on the passive material response of infarcted left ventricles. Methods. Three-dimensional finite element models of the left ventricle were developed using three-dimensional echocardiography data from sheep with a treated and untreated anteroapical infarct, to estimate the material properties (stiffness) in the infarct and remote regions. This was accomplished by matching experimentally determined left ventricular volumes, and minimizing radial strain in the treated infarct, which is indicative of akinesia. The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction, and an elastance model for active fiber stress was incorporated. Results. It was found that the passive stiffness parameter, C, in the treated infarct region is increased by nearly 345 times the healthy remote value. Additionally, the average myofiber stress in the treated left ventricle was significantly reduced in both the remote and infarct regions. Conclusions. Overall, injection of tissue filler into the infarct was found to render it akinetic and reduce stress in the left ventricle, which could limit the adverse remodeling that leads to heart failure. (Ann Thorac Surg 2011;92:935-41) (C) 2011 by The Society of Thoracic Surgeons C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. Dept Vet Affairs Med Ctr, San Francisco, CA USA. Univ Penn, Gorman Cardiovasc Res Grp, Philadelphia, PA 19104 USA. Stanford Univ, Dept Mech Engn, Palo Alto, CA 94304 USA. RP Guccione, JM (reprint author), San Francisco VA Med Ctr, Div Surg Serv 112D, 4150 Clement St, San Francisco, CA 94121 USA. EM guccionej@surgery.ucsf.edu RI Kuhl, Ellen/G-4444-2011 OI Kuhl, Ellen/0000-0002-6283-935X FU National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD [HL84431, HL86400, HL63348, HL77921, HL99172]; American Heart Association, Dallas, TX FX This work was supported by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD (HL84431, HL86400, HL63348, HL77921, and HL99172). Drs Robert Gorman and Joseph Gorman are supported by individual Established Investigator Awards from the American Heart Association, Dallas, TX. NR 28 TC 29 Z9 29 U1 2 U2 9 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 SEP PY 2011 VL 92 IS 3 BP 935 EP 941 DI 10.1016/j.athoracsur.2011.04.089 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 811WJ UT WOS:000294247400035 PM 21871280 ER PT J AU Song, JJ Kim, SS Liu, ZL Madsen, JC Mathisen, DJ Vacanti, JP Ott, HC AF Song, Jeremy J. Kim, Sam S. Liu, Zhilin Madsen, Joren C. Mathisen, Douglas J. Vacanti, Joseph P. Ott, Harald C. TI Enhanced In Vivo Function of Bioartificial Lungs in Rats SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the Society-of-Thoracic-Surgeons / Surgical Motion Picture Session CY JAN 31-FEB 02, 2011 CL San Diego, CA SP Soc Thorac Surg ID STEM-CELLS; TRANSPLANTATION; CULTURE; MATRIX AB Background. More than 11 million Americans live with chronic lung disease; in search for an alternative to donor organs, we attempted to regenerate lungs based on perfusion decellularized lung scaffolds that can be transplanted similar to a donor organ. Methods. Cadaveric rat lungs were decellularized by detergent perfusion. Resulting scaffolds were mounted in bioreactors and seeded with endothelial and fetal lung cells. Biomimetic organ culture was maintained for 7 days. Resulting bioartificial left lungs were transplanted in orthotopic position after left pneumonectomy in rats. Cadaveric left lung transplants and pneumonectomies served as controls. Blood gas analyses, compliance testing, and fluoroscopies were performed on postoperative days 1, 7, and 14. Lungs were removed for final analysis on day 14. Results. Perfusion decellularization of cadaveric lungs yielded acellular scaffolds with intact architecture and matrix composition. Alveolar volumes, number, and size were comparable in bioartificial and native lungs, as were gas exchange, vital capacity and compliance in vitro. After using improved graft preservation and postoperative weaning protocols, animals could be fully recovered, and bioartificial lung constructs provided oxygenation as long as 7 days at levels comparable to cadaveric lung transplants. Compliance, gas exchange, and radiographic appearance gradually declined over the subsequent 7 days owing to progressive graft consolidation and inflammation. Conclusions. Perfusion decellularization of cadaveric lungs yields intact scaffolds that can be seeded with cells to generate bioartificial lung grafts. After orthotopic transplantation, grafts are perfused by the recipient's circulation, ventilated through the recipient's airway and provide gas exchange in vivo for 7 days. (Ann Thorac Surg 2011;92:998-1006) (C) 2011 by The Society of Thoracic Surgeons C1 [Ott, Harald C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Surg,Dept Surg, Boston, MA 02114 USA. Harvard Stem Cell Inst, Boston, MA USA. RP Ott, HC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg,Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA. EM hott@partners.org NR 24 TC 79 Z9 82 U1 2 U2 21 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 SEP PY 2011 VL 92 IS 3 BP 998 EP 1006 DI 10.1016/j.athoracsur.2011.05.018 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 811WJ UT WOS:000294247400048 PM 21871290 ER PT J AU Merritt, RE Reznik, SI DaSilva, MC Sugarbaker, DJ Whyte, RI Donahue, DM Hoang, CD Smythe, WR Shrager, JB AF Merritt, Robert E. Reznik, Scott I. DaSilva, Marcelo C. Sugarbaker, David J. Whyte, Richard I. Donahue, Dean M. Hoang, Chuong D. Smythe, W. Roy Shrager, Joseph B. TI Benign Emptying of the Postpneumonectomy Space SO ANNALS OF THORACIC SURGERY LA English DT Article ID THORACIC-SURGERY DATABASE; BRONCHOPLEURAL FISTULA; LONG-TERM; MANAGEMENT; EMPYEMA; PNEUMONECTOMY; SOCIETY AB Background. A fall in the postpneumonectomy fluid level is considered a sign of bronchopleural fistula (BPF) requiring surgical intervention. We have discovered however that in rare asymptomatic patients, this event may not require aggressive surgical treatment. Methods. After seeing a case of benign emptying of the postpneumonectomy space (BEPS), we surveyed 28 surgeons to determine its incidence and characteristics. Results. Forty-four cases of BEPS were reported by 23 survey respondents. Among 7 fully documented cases from 4 institutions, we defined the following criteria: the patient must be asymptomatic (no fever, white cell count elevation, or fluid expectoration), negative culture results if fluid sampled (patient not receiving antibiotics), no BPF at bronchoscopy or ventilation scintigraphy scan (or both), and recovery without drainage, or retrospective assessment that the intervention was unnecessary. BEPS occurred between 5 days and 152 days after pneumonectomy (6 cases right pneumonectomy and 1 case left pneumonectomy). Four patients underwent no treatment, 1 patient underwent thoracoscopic exploration (sterile) and closure after antibiotic irrigation, 1 patient under-went thoracoscopic exploration alone, and 1 patient underwent open window thoracostomy (sterile) with eventual closure. In all 7 patients (except the patient who underwent the open window procedure) the space refilled within 8 weeks; no patient experienced a subsequent empyema/BPF. Four patients who met the initial criteria for BEPS went on to experience empyema. The incidence of BEPS appears related to pneumonectomy volume, particularly extrapleural pneumonectomy. Using surgeon volume assumptions, the incidence of BEPS is 0.65%. Conclusions. To our knowledge, BEPS is a previously unreported occurrence. We hypothesize that it results from postoperative intrapleural pressure shifts, with or without a microscopic BPF, that drive fluid out of the pleural space while failing to cause contamination. Awareness of BEPS' existence may allow surgeons to safely avoid open drainage procedures occasionally in patients who experience an asymptomatic fall in fluid level. (Ann Thorac Surg 2011;92:1076-82) (C) 2011 by The Society of Thoracic Surgeons C1 [Merritt, Robert E.] Stanford Hosp & Clin, Div Thorac Surg, Stanford Sch Med, Stanford, CA 94305 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. Texas A&M Hlth Sci Ctr, Scott & White Healthcare Syst, Temple, TX USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Merritt, RE (reprint author), Stanford Hosp & Clin, Div Thorac Surg, Stanford Sch Med, 300 Pasteur Dr, Stanford, CA 94305 USA. EM rmerritt@stanford.edu NR 15 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2011 VL 92 IS 3 BP 1076 EP 1082 DI 10.1016/j.athoracsur.2011.04.082 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 811WJ UT WOS:000294247400065 PM 21871304 ER PT J AU Pereda, D Sundt, TM AF Pereda, Daniel Sundt, Thoralf M., III TI Composite Root Replacement at the Level of the Aortoventricular Junction SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID AORTIC ROOT; ASCENDING AORTA; EXPERIENCE; SURGERY AB Composite root replacement has become the gold standard treatment for many root pathologies. The results are excellent; however, postoperative heart block does occur. We have adopted a modification of the conventional suture placement techniques aiming to reduce this complication. By skeletonizing the root and passing the valve sutures transmurally at the level of the anatomic aortoventricular junction rather than through the surgical annulus we give wide berth to the conduction system. This also facilitates placement of a hemostatic running suture around the prosthesis, if desired. We have seen a reduction in heart block requiring pacemaker implantation without prolongation of bypass or cross-clamp times. (Ann Thorac Surg 2011;92:e61-3) (C) 2011 by The Society of Thoracic Surgeons C1 [Sundt, Thoralf M., III] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Mayo Clin, Div Cardiovasc Surg, Rochester, MN USA. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St, Boston, MA 02114 USA. EM tsundt@partners.org NR 8 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2011 VL 92 IS 3 BP E61 EP E63 DI 10.1016/j.athoracsur.2011.04.114 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 811WJ UT WOS:000294247400008 PM 21871259 ER PT J AU Brody, AL Mandelkern, MA London, ED Khan, A Kozman, D Costello, MR Vellios, EE Archie, MM Bascom, R Mukhin, AG AF Brody, Arthur L. Mandelkern, Mark A. London, Edythe D. Khan, Aliyah Kozman, Daniel Costello, Matthew R. Vellios, Evan E. Archie, Meena M. Bascom, Rebecca Mukhin, Alexey G. TI Effect of Secondhand Smoke on Occupancy of Nicotinic Acetylcholine Receptors in Brain SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; INFANT-DEATH-SYNDROME; CIGARETTE-SMOKE; PASSIVE SMOKING; BINDING-PROPERTIES; IN-VITRO; PET; EXPOSURE; DEPENDENCE; BLOOD AB Context: Despite progress in tobacco control, secondhand smoke (SHS) exposure remains prevalent worldwide and is implicated in the initiation and maintenance of cigarette smoking. Objective: To determine whether moderate SHS exposure results in brain alpha(4)beta(2)* nicotinic acetylcholine receptor (nAChR) occupancy. Design, Setting, and Participants: Positron emission tomography scanning and the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (also known as 2-[(18)F]fluoro-A-85380, or 2-FA) were used to determine alpha(4)beta(2)* nAChR occupancy from SHS exposure in 24 young adult participants (11 moderately dependent cigarette smokers and 13 nonsmokers). Participants underwent two bolus-plus-continuous-infusion 2-FA positron emission tomography scanning sessions during which they sat in the passenger's seat of a car for 1 hour and either were exposed to moderate SHS or had no SHS exposure. The study took place at an academic positron emission tomography center. Main Outcome Measure: Changes induced by SHS in 2-FA specific binding volume of distribution as a measure of alpha(4)beta(2)* nAChR occupancy. Results: An overall multivariate analysis of variance using specific binding volume of distribution values revealed a significant main effect of condition (SHS vs control) (F(1,22)=42.5, P<.001) but no between-group (smoker vs nonsmoker) effect. Exposure to SHS led to a mean 19% occupancy of brain alpha(4)beta(2)* nAChRs (1-sample t test, 2-tailed, P<.001). Smokers had both a mean 23% increase in craving with SHS exposure and a correlation between thalamic alpha(4)beta(2)* nAChR occupancy and craving alleviation with subsequent cigarette smoking (Spearman rho=-0.74, P=.01). Conclusions: Nicotine from SHS exposure results in substantial brain alpha(4)beta(2)* nAChR occupancy in smokers and nonsmokers. Study findings suggest that such exposure delivers a priming dose of nicotine to the brain that contributes to continued cigarette use in smokers. This study has implications for both biological research into the link between SHS exposure and cigarette use and public policy regarding the need to limit SHS exposure in cars and other enclosed spaces. C1 [Brody, Arthur L.; London, Edythe D.; Khan, Aliyah; Kozman, Daniel; Costello, Matthew R.; Vellios, Evan E.; Archie, Meena M.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. [Brody, Arthur L.; Mandelkern, Mark A.; London, Edythe D.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Radiol, Los Angeles, CA USA. [Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. [Bascom, Rebecca] Penn State Univ, Dept Pulmonol, Hershey, PA USA. [Mukhin, Alexey G.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, 300 UCLA Med Plaza,Ste 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU Philip Morris USA; Tobacco-Related Disease Research Program [16RT-0098]; National Institute on Drug Abuse [R01 DA20872]; Veterans Affairs Type I Merit Review Award; Office of National Drug Control Policy [DABT63-00-C-1003] FX Drs London and Mukhin received support from Philip Morris USA for research other than the project presented here.; This study was supported by grant 16RT-0098 from the Tobacco-Related Disease Research Program (Dr Brody), grant R01 DA20872 from the National Institute on Drug Abuse (Dr Brody), a Veterans Affairs Type I Merit Review Award (Dr Brody), grant DABT63-00-C-1003 from the Office of National Drug Control Policy (Dr London), and endowments from the Richard Metzner Chair in Clinical Neuropharmacology (Dr Brody), the Thomas P. and Katherine K. Pike Chair in Addiction Studies (Dr London), and the Marjorie Greene Family Trust (Dr London). NR 70 TC 25 Z9 26 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2011 VL 68 IS 9 BP 953 EP 960 DI 10.1001/archgenpsychiatry.2011.51 PG 8 WC Psychiatry SC Psychiatry GA 815OU UT WOS:000294535700011 PM 21536968 ER PT J AU Li, G Wang, LY Shofer, JB Thompson, ML Peskind, ER McCormick, W Bowen, JD Crane, PK Larson, EB AF Li, Ge Wang, Lucy Y. Shofer, Jane B. Thompson, Mary Lou Peskind, Elaine R. McCormick, Wayne Bowen, James D. Crane, Paul K. Larson, Eric B. TI Temporal Relationship Between Depression and Dementia Findings From a Large Community-Based 15-Year Follow-up Study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; WHITE-MATTER LESIONS; LATE-LIFE DEPRESSION; ALZHEIMER-DISEASE; MAJOR DEPRESSION; RISK-FACTOR; CES-D; SYMPTOMS; COMMUNITY; DECLINE AB Context: Late-life depression is associated with increased risk of dementia, but the temporal relationship between depression and development of dementia remains unclear. Objectives: To examine the association between risk of dementia and baseline depressive symptoms; history of depression, particularly early-life (<50 years) vs late-life depression (>= 50 years); and individual domains of the Center for Epidemiologic Studies Depression Scale. Design: A large cohort with initially nondemented participants was followed up biennially for up to 15 years. Baseline depressive symptoms were assessed using the 11-item version of the Center for Epidemiologic Studies Depression Scale; presence of significant depressive symptoms was defined as a score of 11 or greater. Self-reported history of depression was collected at the baseline interview. Cox proportional hazards regression was used to assess the association between depression and dementia risk. Setting: Population-based cohort drawn from members of the Group Health Cooperative in Seattle, Washington. Participants: A cohort of 3410 participants without dementia aged at least 65 years. Results: During a mean of 7.1 years of follow-up, 658 participants (19.3%) developed dementia. At baseline, 9.4% of participants had presence of significant depressive symptoms, and 21.2% reported a history of depression. The adjusted hazard ratio for dementia associated with baseline depressive symptoms was 1.71 (95% confidence interval, 1.37-2.13), after adjusting for age at entry, sex, educational level, and wave of enrollment. Compared with participants without depression history, those with late-life depression were at increased dementia risk (adjusted hazard ratio, 1.46; 95% confidence interval, 1.16-1.84), but early-life depression had no association with dementia risk (1.10 [0.83-1.47]). Depressed mood (adjusted hazard ratio, 1.48; 95% confidence interval, 1.25-1.76) and perceived performance difficulty (1.39 [1.15-1.67]) were independently associated with dementia. Conclusion: This study confirmed that late-life depression is associated with increased risk of dementia and supplied evidence that late-life depression may be an early manifestation of dementia rather than increasing risk for dementia. C1 [Li, Ge; Wang, Lucy Y.; Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, Mental Illness Res & Educ Clin Ctr, Seattle, WA 98108 USA. [Li, Ge; Wang, Lucy Y.; Shofer, Jane B.; Peskind, Elaine R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Thompson, Mary Lou] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [McCormick, Wayne; Crane, Paul K.; Larson, Eric B.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Bowen, James D.] Swedish Med Ctr, Swedish Neurosci Inst, Englewood, CO 80110 USA. [Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Li, G (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res & Educ Clin Ctr, 1660 S Columbian Way,Mail Code S-116-6-E, Seattle, WA 98108 USA. EM gli@u.washington.edu RI Crane, Paul/C-8623-2014; OI Crane, Paul/0000-0003-4278-7465 FU National Institute of Aging [AG033693, AG006781, AG05136]; Department of Veterans Affairs; VA Puget Sound Health Care System FX This study was supported by grants AG033693, AG006781, and AG05136 from the National Institute of Aging and by the Department of Veterans Affairs and partially supported by resources from the VA Puget Sound Health Care System. NR 38 TC 40 Z9 43 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2011 VL 68 IS 9 BP 970 EP 977 PG 8 WC Psychiatry SC Psychiatry GA 815OU UT WOS:000294535700013 PM 21893662 ER PT J AU Ng, A Xavier, RJ AF Ng, Aylwin Xavier, Ramnik J. TI Leucine-rich repeat (LRR) proteins Integrators of pattern recognition and signaling in immunity SO AUTOPHAGY LA English DT Editorial Material DE systems biology; pathogen sensors; pathogen response; antibacterial; inflammation; autophagy; bioinformatics; computational biology AB The leucine-rich repeats (LRR)-containing domain is evolutionarily conserved in many proteins associated with innate immunity in plants, invertebrates and vertebrates. Serving as a first line of defense, the innate immune response is initiated through the sensing of pathogen-associated molecular patterns (PAMPs). In plants, NBS (nucleotide-binding site)-LRR proteins provide recognition of pathogen products of avirulence (AVR) genes. LRRs also promote interaction between LRR proteins as observed in receptor-coreceptor complexes. In mammals, toll-like receptors (TLRs) and NOD-like receptors (NLRs) through their LRR domain, sense molecular determinants from a structurally diverse set of bacterial, fungal, parasite and viral-derived components. In humans, at least 34 LRR proteins are implicated in diseases. Most LRR domains consist of 2-45 leucine-rich repeats, with each repeat about 20-30 residues long. Structurally, LRR domains adopt an arc or horseshoe shape, with the concave face consisting of parallel beta-strands and the convex face representing a more variable region of secondary structures including helices. Apart from the TLRs and NLRs, most of the 375 human LRR proteins remain uncharacterized functionally. We incorporated computational and functional analyses to facilitate multifaceted insights into human LRR proteins and outline a few approaches here. C1 [Ng, Aylwin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Cambridge, MA 02138 USA. Broad Inst MIT & Harvard, Cambridge, MA USA. RP Ng, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Cambridge, MA 02138 USA. EM ang@ccib.mgh.harvard.edu NR 0 TC 9 Z9 10 U1 3 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD SEP PY 2011 VL 7 IS 9 BP 1082 EP 1084 DI 10.4161/auto.7.9.16464 PG 3 WC Cell Biology SC Cell Biology GA 814SI UT WOS:000294477100020 PM 21606681 ER PT J AU Eapen, M Le Rademacher, J Antin, JH Champlin, RE Carreras, J Fay, J Passweg, JR Tolar, J Horowitz, MM Marsh, JCW Deeg, HJ AF Eapen, Mary Le Rademacher, Jennifer Antin, Joseph H. Champlin, Richard E. Carreras, Jeanette Fay, Joseph Passweg, Jakob R. Tolar, Jakub Horowitz, Mary M. Marsh, Judith C. W. Deeg, H. Joachim TI Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia SO BLOOD LA English DT Article ID MARROW TRANSPLANTATION; PATHOPHYSIOLOGY; GVHD AB Outcome after unrelated donor bone marrow (BM) transplantation for severe aplastic anemia (SAA) has improved, with survival rates now approximately 75%. Increasing use of peripheral blood stem and progenitor cells (PBPCs) instead of BM as a graft source prompted us to compare outcomes of PBPC and BM transplantation for SAA. We studied 296 patients receiving either BM (n = 225) or PBPC (n = 71) from unrelated donors matched at human leukocyte antigen-A, -B, -C, -DRB1. Hematopoietic recovery was similar after PBPC and BM transplantation. Grade 2 to 4 acute graft-versus-host disease risks were higher after transplantation of PBPC compared with BM (hazard ratio = 1.68, P = .02; 48% vs 31%). Chronic graft-versus-host disease risks were not significantly different after adjusting for age at transplantation (hazard ratio = 1.39, P = .14). Mortality risks, independent of age, were higher after PBPC compared with BM transplantation (hazard ratio = 1.62, P = .04; 76% vs 61%). These data indicate that BM is the preferred graft source for unrelated donor transplantation in SAA. (Blood. 2011; 118(9):2618-2621) C1 [Eapen, Mary; Le Rademacher, Jennifer; Carreras, Jeanette; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Champlin, Richard E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fay, Joseph] Baylor Univ, Med Ctr, Dallas, TX USA. [Passweg, Jakob R.] Univ Basel, Basel, Switzerland. [Tolar, Jakub] Univ Minnesota, Minneapolis, MN USA. [Marsh, Judith C. W.] Kings Coll London, London WC2R 2LS, England. [Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Eapen, M (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM meapen@mcw.edu OI Tolar, Jakub/0000-0002-0957-4380 FU National Cancer Institute [U24-CA76518]; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases; Heath Resources and Services Administration [HHSH234200637015C]; Office of Naval Research, Department of Navy [N00014-06-01-0704] FX This work was supported by the National Cancer Institute (Public Health Service grant U24-CA76518), the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Heath Resources and Services Administration (HHSH234200637015C), and the Office of Naval Research, Department of Navy to the National Marrow Donor Program (N00014-06-01-0704). NR 14 TC 60 Z9 67 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2011 VL 118 IS 9 BP 2618 EP 2621 DI 10.1182/blood-2011-05-354001 PG 4 WC Hematology SC Hematology GA 814SC UT WOS:000294476400035 PM 21677312 ER PT J AU Gesty-Palmer, D Luttrell, LM AF Gesty-Palmer, Diane Luttrell, Louis M. TI 'Biasing' the parathyroid hormone receptor: A novel anabolic approach to increasing bone mass? SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE G-protein-coupled receptor (GPCR); GPCR signalling; beta-arrestin; biased agonism; functional selectivity; parathyroid hormone (PTH); type I parathyroid hormone receptor (PTH1R); bone metabolism; osteoporosis ID PROTEIN-COUPLED RECEPTORS; RAT OSTEOBLASTIC CELLS; C ACTIVATION DOMAIN; BETA-ARRESTIN; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; DEPENDENT PATHWAYS; GROWTH-HORMONE; KIDNEY-CELLS; KINASE AB 'Functional selectivity' refers to the ability of a ligand to activate and/or inhibit only a subset of the signals capable of emanating from its cognate G-protein-coupled receptor (GPCR). Whereas conventional GPCR agonism and antagonism can be viewed as modulating the quantity of efficacy, functionally selective or 'biased' ligands qualitatively change the nature of information flow across the plasma membrane, raising the prospect of drugs with improved therapeutic efficacy or reduced side effects. Nonetheless, there is little experimental evidence that biased ligands offer advantages over conventional agonists/antagonists in vivo. Recent work with the type I parathyroid hormone receptor (PTH(1)R) suggests that biased ligands that selectively activate G-protein-independent arrestin-mediated signalling pathways may hold promise in the treatment of osteoporosis. Parathyroid hormone (PTH) is a principle regulator of bone and calcium metabolism. In bone, PTH exerts complex effects; promoting new bone formation through direct actions on osteoblasts while simultaneously stimulating bone loss through indirect activation of osteoclastic bone resorption. Although the conventional PTH(1)R agonist teriparatide, PTH(1-34), is effective in the treatment of osteoporosis, its utility is limited by its bone-resorptive effects and propensity to promote hypercalcaemia/hypercalcuria. In contrast, D-Trp(12),Tyr(34)-bPTH(7-34) (PTH-beta arr), an arrestin pathway-selective agonist for the PTH(1)R, induces anabolic bone formation independent of classic G-protein-coupled signalling mechanisms. Unlike PTH(1-34), PTH-beta arr appears to 'uncouple' the anabolic effects of PTH1R activation from its catabolic and calcitropic effects. Such findings offer evidence that arrestin pathway-selective GPCR agonists can elicit potentially beneficial effects in vivo that cannot be achieved using conventional agonist or antagonist ligands. C1 [Gesty-Palmer, Diane] Duke Univ, Med Ctr, Dept Med, Div Endocrinol & Metab, Durham, NC 27710 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Gesty-Palmer, Diane] Durham Vet Affairs Med Ctr, Durham, NC USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Gesty-Palmer, D (reprint author), Duke Univ, Med Ctr, Dept Med, Div Endocrinol & Metab, Box 103015, Durham, NC 27710 USA. EM gesty001@mc.duke.edu FU National Institutes of Health [DK64353, DK55524, HD043446]; Arthritis Foundation; Research Services of the Charleston, SC and Durham, NC Veterans Affairs Medical Centers FX This work was supported by National Institutes of Health Grants DK64353 (LML, DGP), DK55524 (LML) and HD043446 (DGP); the Arthritis Foundation (DGP) and the Research Services of the Charleston, SC and Durham, NC Veterans Affairs Medical Centers. NR 66 TC 19 Z9 20 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 2011 VL 164 IS 1 BP 59 EP 67 DI 10.1111/j.1476-5381.2011.01450.x PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 810LL UT WOS:000294126700005 PM 21506957 ER PT J AU Blois, J Smith, A Josephson, L AF Blois, Joseph Smith, Adam Josephson, Lee TI The slow cell death response when screening chemotherapeutic agents SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Apoptosis; Annexin V; Chemotherapy; Cell death; Screening; Cytotoxicity ID IN-VITRO; CHEMOSENSITIVITY; APOPTOSIS; ASSAY; CYTOTOXICITY; CISPLATIN; NECROSIS; PROTEIN; CANCER; INJURY AB To examine the correlation between cell death and a common surrogate of death used in screening assays, we compared cell death responses to those obtained with the sulforhodamine B (SRB) cell protein-based "cytotoxicity" assay. With the SRB assay, the Hill equation was used to obtain an IC50 and final cell mass, or cell mass present at infinite agent concentrations, with eight adherent cell lines and four agents (32 agent/cell combinations). Cells were treated with high agent concentrations (well above the SRB IC50) and the death response determined as the time-dependent decrease in cells failing to bind both annexin V and vital fluorochromes by flow cytometry. Death kinetics were categorized as fast (5/32) (similar to the reference nonadherent Jurkat line), slow (17/32), or none (10/32), despite positive responses in the SRB assay in all cases. With slow cell death, a single exposure to a chemotherapeutic agent caused a slow, progressive increase in dead (necrotic) and dying (apoptotic) cells for at least 72 h. Cell death (defined by annexin and/or fluorochrome binding) did not correlate with the standard SRB "cytotoxicity" assay. With the slow cell death response, a single exposure to an agent caused a slow conversion from vital to apoptotic and necrotic cells over at least 72 h (the longest time point examined). Here, increasing the time of exposure to agent concentrations modestly above the SRB IC50 provides a method of maximizing cell kill. If tumors respond similarly, sustained low doses of chemotherapeutic agents, rather than a log-kill, maximum tolerated dose strategy may be an optimal strategy of maximizing tumor cell death. C1 [Blois, Joseph; Smith, Adam; Josephson, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging CTNMI, Charlestown, MA 02129 USA. RP Josephson, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Translat Nucl Med & Mol Imaging CTNMI, 149 13th St, Charlestown, MA 02129 USA. EM ljosephson@mgh.harvard.edu FU NIH [P50CA086355, EB004472, EB009691] FX Financial support: NIH R01's EB004472 and EB009691 and by NIH P50CA086355. NR 21 TC 4 Z9 4 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 2011 VL 68 IS 3 BP 795 EP 803 DI 10.1007/s00280-010-1549-9 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 813CW UT WOS:000294345400027 PM 21193989 ER PT J AU Skates, SJ Mai, P Horick, NK Piedmonte, M Drescher, CW Isaacs, C Armstrong, DK Buys, SS Rodriguez, GC Horowitz, IR Berchuck, A Daly, MB Domchek, S Cohn, DE Van Le, L Schorge, JO Newland, W Davidson, SA Barnes, M Brewster, W Azodi, M Nerenstone, S Kauff, ND Fabian, CJ Sluss, PM Nayfield, SG Kasten, CH Finkelstein, DM Greene, MH Lu, K AF Skates, Steven J. Mai, Phuong Horick, Nora K. Piedmonte, Marion Drescher, Charles W. Isaacs, Claudine Armstrong, Deborah K. Buys, Saundra S. Rodriguez, Gustavo C. Horowitz, Ira R. Berchuck, Andrew Daly, Mary B. Domchek, Susan Cohn, David E. Van Le, Linda Schorge, John O. Newland, William Davidson, Susan A. Barnes, Mack Brewster, Wendy Azodi, Masoud Nerenstone, Stacy Kauff, Noah D. Fabian, Carol J. Sluss, Patrick M. Nayfield, Susan G. Kasten, Carol H. Finkelstein, Dianne M. Greene, Mark H. Lu, Karen TI Large Prospective Study of Ovarian Cancer Screening in High-Risk Women: CA125 Cut-Point Defined by Menopausal Status SO CANCER PREVENTION RESEARCH LA English DT Article ID REDUCING SALPINGO-OOPHORECTOMY; SERUM CA-125 LEVELS; TRIAL; PROSTATE; LUNG AB Previous screening trials for early detection of ovarian cancer in postmenopausal women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in this population yielding a 2% false positive rate, whereas the same cut-point in trials of premenopausal women results in substantially higher false positive rates. We investigated demographic and clinical factors predicting CA125 distributions, including 98th percentiles, in a large population of high-risk women participating in two ovarian cancer screening studies with common eligibility criteria and screening protocols. Baseline CA125 values and clinical and demographic data from 3,692 women participating in screening studies conducted by the National Cancer Institute-sponsored Cancer Genetics Network and Gynecologic Oncology Group were combined for this preplanned analysis. Because of the large effect of menopausal status on CA125 levels, statistical analyses were conducted separately in pre- and postmenopausal subjects to determine the impact of other baseline factors on predicted CA125 cut-points on the basis of 98th percentile. The primary clinical factor affecting CA125 cut-points was menopausal status, with premenopausal women having a significantly higher cut-point of 50 U/mL, while in postmenopausal subjects the standard cut-point of 35 U/mL was recapitulated. In premenopausal women, current oral contraceptive (OC) users had a cut-point of 40 U/mL. To achieve a 2% false positive rate in ovarian cancer screening trials and in high-risk women choosing to be screened, the cut-point for initial CA125 testing should be personalized primarily for menopausal status (50 for premenopausal women, 40 for premenopausal on OC, and 35 for postmenopausal women). Cancer Prev Res; 4(9); 1401-8. (C) 2011 AACR. C1 [Skates, Steven J.; Horick, Nora K.; Finkelstein, Dianne M.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Sluss, Patrick M.] Massachusetts Gen Hosp, Clin Pathol Core Labs, Boston, MA 02114 USA. [Mai, Phuong] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Nayfield, Susan G.; Kasten, Carol H.] NCI, Epidemiol & Genet Res Program, Div Canc Control & Prevent Sci, Bethesda, MD 20892 USA. [Kasten, Carol H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Off Director, Bethesda, MD USA. [Piedmonte, Marion] Roswell Pk Canc Inst, GOG Stat & Data Ctr, Buffalo, NY 14263 USA. [Drescher, Charles W.] Swedish Med Ctr, Dept Gynecol, Seattle, WA USA. [Isaacs, Claudine] Georgetown Univ, Dept Med & Oncol, Lombardi Comprehens Ctr, Washington, DC USA. [Armstrong, Deborah K.] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. [Buys, Saundra S.] Huntsman Canc Inst, Salt Lake City, UT USA. [Rodriguez, Gustavo C.] NorthShore Univ Hlth Syst, NW Healthcare, Evanston, IL USA. [Horowitz, Ira R.] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. [Berchuck, Andrew] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Daly, Mary B.] Univ Penn, Fox Chase Canc Ctr, Dept Clin Genet, Philadelphia, PA 19104 USA. [Domchek, Susan] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Cohn, David E.] Ohio State Univ, Coll Med, Div Gynecol Oncol, James Canc Hosp, Columbus, OH 43210 USA. [Cohn, David E.] Ohio State Univ, Coll Med, Solove Res Inst, Columbus, OH 43210 USA. [Van Le, Linda] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Newland, William] Iowa Methodist Med Ctr, Dept Obstet & Gynecol, John Stoddard Canc Ctr, Des Moines, IA USA. [Davidson, Susan A.] Univ Colorado Denver, Dept Obstet & Gynecol, Div Gynecol Oncol, Aurora, CO USA. [Barnes, Mack] Univ Alabama, Birmingham, AL USA. [Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Div Surg, Houston, TX 77030 USA. [Nayfield, Susan G.] Univ Florida, Coll Med, Dept Aging & Geriatr Res, Inst Aging, Gainesville, FL USA. [Fabian, Carol J.] Univ Kansas, Ctr Canc, Westwood, KS USA. [Kauff, Noah D.] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA. [Kauff, Noah D.] Mem Sloan Kettering Canc Ctr, Gynecol Serv, New York, NY 10021 USA. [Nerenstone, Stacy] Hartford Hosp, Cent Connecticut Canc Consortium, Hartford, CT 06115 USA. [Azodi, Masoud] Yale Univ, Dept Obstet & Gynecol, Div Gynecol Oncol, New Haven, CT USA. [Brewster, Wendy] Univ Calif Irvine, Dept Obstet & Gynecol, Div Gynecol Oncol, Sch Med, Orange, CA 92668 USA. RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 50 Staniford St,Suite 560, Boston, MA 02114 USA. EM dfinkelstein@partners.org OI Kauff, Noah/0000-0001-7242-6156 FU NCI [CA078284, CA078134, CA078164, CA078156, CA078148, CA078146, CA078174, CA078157, CA078142, HHSN2612007440000C, CA086381, CA152990]; Cancer Genetics Network; Ovarian SPORE program; Early Detection Research Network; Fujirebio Diagnostics Inc.; NCI/NIH; Cancer Prevention and Control Committee FX The ROCA study was supported mostly by research grants/contracts from NCI (CA078284, CA078134, CA078164, CA078156, CA078148, CA078146, CA078174, CA078157, CA078142, HHSN2612007440000C, CA086381, and CA152990) to sites in the Cancer Genetics Network, the Ovarian SPORE program, and the Early Detection Research Network; Fujirebio Diagnostics Inc., supported the study for one year after NCI funding ended. P. Mai and M. H. Greene were supported by the Intramural Research Program, NCI/NIH. The Gynecologic Oncology Group's participation (GOG0199) was supported by its Cancer Prevention and Control Committee. Programming assistance from Ying Zhou MS is gratefully acknowledged. In addition to the clinical site principal investigators who enrolled more than 50 patients in the CGN study and are listed as authors, the following clinical sites and PI's contributed patients to the study and are gratefully acknowledged: Holly Gallion MD (Magee Women's Hospital 46), Powel Brown MD(Baylor College of Medicine 41), Alex Miller MD (University of Texas Health Sciences Center San Antonio 38), Paula Ryan MD PhD (Massachusetts General Hospital 21), Judy Garber MD PhD (Dana Farber Cancer Institute 20), Henry Lynch MD (Creighton University 19), James Evans MD PhD (University of North Carolina 15), Henry Lynch MD (EDRN High Risk Registry 12), Lee-May Chen MD (University of California San Francisco 10), Olufunmilayo Olopade MD (University of Chicago 3), Thomas Caputo MD(Cornell University 3). The CGN study was conducted under the auspices of the Cancer Genetics Network with the support of the CGN PI's which is gratefully acknowledged: Deborah Bowen PhD (Fred Hutchinson Cancer Center), Claudine Isaacs MD (Georgetown University), Constance Griffin MD (Johns Hopkins University), Geraldine Mineau PhD (Huntsman Cancer Institute), Joellen Schildkraut PhD (Duke University), Louise Strong MD (MD Anderson Cancer Center), Susan Domchek MD (University of Pennsylvannia), Gail Tomlinson MD PhD (University of Texas Southwestern Medical Center), Dennis Ahnen MD (University of Colorado), Hoda Anton-Culver PhD (University of California Irvine), Sharon Plon MD PhD (Baylor College of Medicine), James Evans MD PhD (University of North Carolina), William Wood MD (Emory University), Alex Miller MD (University of Texas Health Sciences Ctr. at San Antonio). NR 17 TC 14 Z9 15 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD SEP PY 2011 VL 4 IS 9 BP 1401 EP 1408 DI 10.1158/1940-6207.CAPR-10-0402 PG 8 WC Oncology SC Oncology GA 814XI UT WOS:000294490100011 PM 21893500 ER PT J AU Rebbeck, TR Mitra, N Domchek, SM Wan, F Friebel, TM Tran, TV Singer, CF Tea, MKM Blum, JL Tung, N Olopade, OI Weitzel, JN Lynch, HT Snyder, CL Garber, JE Antoniou, AC Peock, S Evans, DG Paterson, J Kennedy, MJ Donaldson, A Dorkins, H Easton, DF Rubinstein, WS Daly, MB Isaacs, C Nevanlinna, H Couch, FJ Andrulis, IL Freidman, E Laitman, Y Ganz, PA Tomlinson, GE Neuhausen, SL Narod, SA Phelan, CM Greenberg, R Nathanson, KL AF Rebbeck, Timothy R. Mitra, Nandita Domchek, Susan M. Wan, Fei Friebel, Tara M. Tran, Teo V. Singer, Christian F. Tea, Muy-Kheng Maria Blum, Joanne L. Tung, Nadine Olopade, Olufunmilayo I. Weitzel, Jeffrey N. Lynch, Henry T. Snyder, Carrie L. Garber, Judy E. Antoniou, Antonis C. Peock, Susan Evans, D. Gareth Paterson, Joan Kennedy, M. John Donaldson, Alan Dorkins, Huw Easton, Douglas F. Rubinstein, Wendy S. Daly, Mary B. Isaacs, Claudine Nevanlinna, Heli Couch, Fergus J. Andrulis, Irene L. Freidman, Eitan Laitman, Yael Ganz, Patricia A. Tomlinson, Gail E. Neuhausen, Susan L. Narod, Steven A. Phelan, Catherine M. Greenberg, Roger Nathanson, Katherine L. CA Epidemiological Study BRCA1 BRCA2 TI Modification of BRCA1-Associated Breast and Ovarian Cancer Risk by BRCA1-Interacting Genes SO CANCER RESEARCH LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISM; UNKNOWN CLINICAL-SIGNIFICANCE; BRCA1/2 MUTATION CARRIERS; DNA-SEQUENCE VARIANTS; BRCA2-INTERACTING PROTEIN; HAPLOTYPE FREQUENCIES; SUSCEPTIBILITY GENE; RAD51; BARD1; PALB2 AB Inherited BRCA1 mutations confer elevated cancer risk. Recent studies have identified genes that encode proteins that interact with BRCA1 as modifiers of BRCA1-associated breast cancer. We evaluated a comprehensive set of genes that encode most known BRCA1 interactors to evaluate the role of these genes as modifiers of cancer risk. A cohort of 2,825 BRCA1 mutation carriers was used to evaluate the association of haplotypes at ATM, BRCC36, BRCC45 (BRE), BRIP1 (BACH1/FANCJ), CTIP, ABRA1 (FAM175A), MERIT40, MRE11A, NBS1, PALB2 (FANCN), RAD50, RAD51, RAP80, and TOPBP1, and was associated with time to breast and ovarian cancer diagnosis. Statistically significant false discovery rate (FDR) adjusted P values for overall association of haplotypes (P(FDR)) with breast cancer were identified at ATM (P(FDR) = 0.029), BRCC45 (P(FDR) = 0.019), BRIP1 (P(FDR) = 0.008), CTIP (P(FDR) = 0.017), MERIT40 (P(FDR) = 0.019), NBS1 (P(FDR) = 0.003), RAD50 (P(FDR) = 0.014), and TOPBP1 (P(FDR) = 0.011). Haplotypes at ABRA1 (P(FDR) = 0.007), BRCC45 (P(FDR) = 0.016 and P(FDR) = 0.005 in two haplotype blocks), and RAP80 (P(FDR) < 0.001) were associated with ovarian cancer risk. Overall, the data suggest that genomic variation at multiple loci that encode proteins that interact biologically with BRCA1 are associated with modified breast cancer and ovarian cancer risk in women who carry BRCA1 mutations. Cancer Res; 71(17); 5792-805. (C)2011 AACR. C1 [Rebbeck, Timothy R.] Univ Penn, Dept Biostat & Epidemiol, Perleman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Rebbeck, Timothy R.; Mitra, Nandita; Wan, Fei; Friebel, Tara M.; Tran, Teo V.] Univ Penn, Ctr Clin Epidemiol & Biostat, Perleman Sch Med, Philadelphia, PA 19104 USA. [Domchek, Susan M.; Greenberg, Roger; Nathanson, Katherine L.] Univ Penn, Dept Med, Perleman Sch Med, Philadelphia, PA 19104 USA. [Daly, Mary B.] Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. [Singer, Christian F.; Tea, Muy-Kheng Maria] Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria. [Blum, Joanne L.] Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Garber, Judy E.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Olopade, Olufunmilayo I.] Univ Chicago, Chicago, IL 60637 USA. [Weitzel, Jeffrey N.; Neuhausen, Susan L.] City Hope Natl Med Ctr, City Hope Comprehens Canc Ctr, Duarte, CA USA. [Weitzel, Jeffrey N.; Neuhausen, Susan L.] City Hope Natl Med Ctr, Dept Populat Sci, Beckman Res Inst, Duarte, CA USA. [Lynch, Henry T.; Snyder, Carrie L.] Creighton Univ, Dept Med, Omaha, NE 68178 USA. [Lynch, Henry T.; Snyder, Carrie L.] Creighton Univ, Dept Prevent Med & Publ Hlth, Omaha, NE 68178 USA. [Antoniou, Antonis C.; Peock, Susan; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England. [Paterson, Joan] Addenbrookes Hosp, Dept Clin Genet, E Anglian Reg Genet Serv, Cambridge, England. [Evans, D. Gareth] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Kennedy, M. John] Trinity Coll Dublin, Acad Unit Clin & Mol Oncol, Dublin, Ireland. [Kennedy, M. John] St James Hosp, Dublin, Ireland. [Donaldson, Alan] St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England. [Dorkins, Huw] Kennedy Galton Ctr, NW Thames Reg Genet Serv, Harrow, Middx, England. [Rubinstein, Wendy S.] NorthShore Univ HealthSyst, Evanston, IL USA. [Isaacs, Claudine] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. [Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland. [Couch, Fergus J.] Mayo Clin, Coll Med, Rochester, MN USA. [Andrulis, Irene L.] Canc Care Ontario, Ontario Canc Genet Network OCGN, Toronto, ON, Canada. [Narod, Steven A.] Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. [Freidman, Eitan; Laitman, Yael] Chaim Sheba Med Ctr, Oncogenet Unit, IL-52621 Tel Hashomer, Israel. [Freidman, Eitan] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Tomlinson, Gail E.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Tomlinson, Gail E.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. [Tomlinson, Gail E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pediat, San Antonio, TX 78229 USA. [Phelan, Catherine M.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. RP Rebbeck, TR (reprint author), Univ Penn, Dept Biostat & Epidemiol, Perleman Sch Med, Abramson Canc Ctr, 217 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rebbeck@upenn.edu RI Andrulis, Irene/E-7267-2013; Tomlinson, George/L-5432-2016; OI Tomlinson, George/0000-0002-9328-6399; Nathanson, Katherine/0000-0002-6740-0901; Nevanlinna, Heli/0000-0002-0916-2976; Evans, Gareth/0000-0002-8482-5784 FU Nebraska Department of Health and Human Services; NIH [5UO1 CA86389, R01-CA083855, R01-CA74415, R01-CA102776, P30-CA051008]; Breast Cancer Research Foundation; Helsinki University; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Cancer Care Ontario; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria; Tasmania and South Australia; Cancer Foundation of Western Australia; Cancer Research UK [C1287/A10118, C1287/A11990, C5047/A8385]; NIHR; Royal Marsden NHS Foundation Trust; NHMRC [145684, 288704, 454508] FX This publication was supported in part by revenue from Nebraska cigarette taxes awarded to Creighton University by the Nebraska Department of Health and Human Services. Support was also received from NIH grants 5UO1 CA86389 (to H. T. Lynch) and R01-CA083855, R01-CA74415 (to S. L. Neuhausen), R01-CA102776, and R01-CA083855 (to T. R. Rebbeck); the Breast Cancer Research Foundation (K. L. Nathanson); and the NIH grants P30-CA051008 (to C. Isaacs). The HEBCS study is supported by the Helsinki University Central Hospital Research Fund, The Academy of Finland (132473), The Finnish Cancer Society, and The Sigrid Juselius Foundation. The OCGN is supported by Cancer Care Ontario. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. EMBRACE is supported by Cancer Research UK grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles, E. Bancroft, and Lucia D'Mello are also supported by Cancer Research UK grant C5047/A8385. Clinical Follow Up Study was funded by NHMRC grants 145684, 288704, and 454508. NR 29 TC 24 Z9 26 U1 0 U2 10 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 SEP 1 PY 2011 VL 71 IS 17 BP 5792 EP 5805 DI 10.1158/0008-5472.CAN-11-0773 PG 14 WC Oncology SC Oncology GA 814LL UT WOS:000294454700021 PM 21799032 ER PT J AU Novina, CD AF Novina, Carl D. TI New insights into the biology of melanomas using a microRNA tool-KIT SO CELL CYCLE LA English DT News Item ID METASTATIC MELANOMA; IMATINIB MESYLATE; CLINICAL-EFFICACY; CELL LINES; SUBTYPES; CANCER C1 [Novina, Carl D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Novina, Carl D.] Harvard Univ, Sch Med, Boston, MA USA. RP Novina, CD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM carl_novina@dfci.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 1 PY 2011 VL 10 IS 17 BP 2828 EP 2829 DI 10.4161/cc.10.17.16571 PG 2 WC Cell Biology SC Cell Biology GA 814TS UT WOS:000294480700008 PM 21869597 ER PT J AU Oxnard, GR Arcila, ME Chmielecki, J Ladanyi, M Miller, VA Pao, W AF Oxnard, Geoffrey R. Arcila, Maria E. Chmielecki, Juliann Ladanyi, Marc Miller, Vincent A. Pao, William TI New Strategies in Overcoming Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-II TRIAL; LEPTOMENINGEAL METASTASES; DRUG-RESISTANCE; T790M MUTATION; EGFR MUTATIONS; ADVANCED NSCLC; CELL-LINE; GEFITINIB; ERLOTINIB; AMPLIFICATION AB The management of non-small cell lung carcinoma (NSCLC) has been transformed by the observation that lung adenocarcinomas harboring mutations in epidermal growth factor receptor (EGFR) are uniquely sensitive to EGFR tyrosine kinase inhibitors (TKI). In these patients, acquired resistance to EGFR-TKI develops after a median of 10 to 14 months, at which time the current standard practice is to switch to conventional cytotoxic chemotherapy. Several possible mechanisms for acquired resistance have been identified, the most common being the development of an EGFR T790M gatekeeper mutation in more than 50% of cases. In this review, we discuss recent advances in the understanding of acquired TKI resistance in EGFR-mutant lung cancer and review therapeutic progress with second generation TKIs and combinations of targeted therapies. Clin Cancer Res; 17(17); 5530-7. (C) 2011 AACR. C1 [Miller, Vincent A.] Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, Dept Med, New York, NY 10021 USA. [Arcila, Maria E.; Chmielecki, Juliann; Ladanyi, Marc; Miller, Vincent A.] Weill Cornell Med Coll, New York, NY USA. [Oxnard, Geoffrey R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oxnard, Geoffrey R.] Harvard Univ, Sch Med, Boston, MA USA. [Pao, William] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Miller, VA (reprint author), Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, Dept Med, 1275 York Ave, New York, NY 10021 USA. EM millerv@mskcc.org RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU National Cancer Institute [P01-CA129243, R01CA121210, U54-CA143798]; American Society of Clinical Oncology FX Supported in part by the National Cancer Institute (P01-CA129243, R01CA121210, U54-CA143798) and by a Young Investigator Award from the American Society of Clinical Oncology. NR 61 TC 146 Z9 153 U1 0 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP 1 PY 2011 VL 17 IS 17 BP 5530 EP 5537 DI 10.1158/1078-0432.CCR-10-2571 PG 8 WC Oncology SC Oncology GA 814SN UT WOS:000294477600002 PM 21775534 ER PT J AU O'Donoghue, ML Mallat, Z Morrow, DA Benessiano, J Sloan, S Omland, T Solomon, SD Braunwald, E Tedgui, A Sabatine, MS AF O'Donoghue, Michelle L. Mallat, Ziad Morrow, David A. Benessiano, Joelle Sloan, Sarah Omland, Torbjorn Solomon, Scott D. Braunwald, Eugene Tedgui, Alain Sabatine, Marc S. TI Prognostic Utility of Secretory Phospholipase A(2) in Patients with Stable Coronary Artery Disease SO CLINICAL CHEMISTRY LA English DT Article ID EPIC-NORFOLK; HEALTHY-MEN; LIPOPROTEIN; EVENTS; ATHEROSCLEROSIS; PLASMA; RISK; MICE; A-002; WOMEN AB BACKGROUND: Secretory phospholipase A(2) (sPLA(2)) may contribute to atherogenesis. To date, few prospective studies have examined the utility of sPLA(2) for risk stratification in coronary artery disease (CAD). METHODS: We measured plasma sPLA(2) activity at baseline in 3708 subjects in the PEACE randomized trial of trandolapril vs placebo in stable CAD. Median follow-up was 4.8 years. We used Cox regression to adjust for demographics, clinical risk factors, apolipoprotein B, apolipoprotein A1, and medications. RESULTS: After multivariable adjustment, sPLA(2) was associated with an increased risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio Q4:Q1 1.55, 95% CI 1.13-2.14) and cardiovascular death or heart failure (1.91, 1.20-3.03). In further multivariable assessment, increased activity levels of sPLA(2) were associated with the risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio 1.47, 95% CI 1.06-2.04), independent of lipoprotein-associated phospholipase A2 mass and C-reactive protein, and modestly improved the area under the curve (AUC) beyond established clinical risk factors (AUC 0.668-0.675, P = 0.01). sPLA(2), N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T all were independently associated with cardiovascular death or heart failure, and each improved risk discrimination (P = 0.02, P < 0.001, P < 0.001, respectively). CONCLUSIONS: sPLA(2) activity provides independent prognostic information beyond established risk markers in patients with stable CAD. These data are encouraging for studies designed to evaluate the role of sPLA(2) as a therapeutic target. (C) 2011 American Association for Clinical Chemistry C1 [O'Donoghue, Michelle L.; Morrow, David A.; Sloan, Sarah; Braunwald, Eugene; Sabatine, Marc S.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Mallat, Ziad; Tedgui, Alain] Paris Cardiovasc Res Ctr PARCC, INSERM, U970, Paris, France. [Mallat, Ziad; Tedgui, Alain] Univ Paris 05, UMR S970, Paris, France. [Benessiano, Joelle] Hop Bichat Claude Bernard, Biochim Lab, F-75877 Paris, France. [Omland, Torbjorn] Akershus Univ Hosp, Div Med, Lorenskog, Norway. RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM modonoghue@partners.org RI Mallat, Ziad/D-4041-2012; Solomon, Scott/I-5789-2013; OI Mallat, Ziad/0000-0003-0443-7878 FU Siemens FX Other Remuneration: Z. Mallat, coinventor on 2 biomarker patents filed by INSERM; D.A. Morrow, consulting fees from Siemens; J. Benessiano, coinventor on 2 biomarker patents filed by INSERM; A. Tedgui, coinventor on 2 biomarker patents filed by INSERM. NR 18 TC 6 Z9 6 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2011 VL 57 IS 9 BP 1311 EP 1317 DI 10.1373/clinchem.2011.166520 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 812JE UT WOS:000294288500018 PM 21784767 ER PT J AU Chen, CC Llado, V Eurich, K Tran, HT Mizoguchi, E AF Chen, Chun-Chuan Llado, Victoria Eurich, Katrin Tran, Hoa T. Mizoguchi, Emiko TI Carbohydrate-binding motif in chitinase 3-like 1 (CHI3L1/YKL-40) specifically activates Akt signaling pathway in colonic epithelial cells SO CLINICAL IMMUNOLOGY LA English DT Article DE Chitinases; Chitin-binding motifs; Epithelial cells; Signal transduction ID HUMAN CARTILAGE GLYCOPROTEIN-39; NECROSIS-FACTOR-ALPHA; SERUM YKL-40; DISEASE-ACTIVITY; PROTEIN FAMILY; ARTICULAR CHONDROCYTES; RHEUMATOID-ARTHRITIS; SERRATIA-MARCESCENS; BACTERIAL ADHESION; MAMMALIAN MEMBER AB Host microbial interactions play a key role during the development of colitis. We have previously shown that chinase 3-like 1 (CHI3L1) is an inducible molecule overexpressed in colonic epithelial cells (CECs) under inflammatory conditions. In this study, we found that chitin-binding motif (CBM) of CHI3L1 is specifically associated with the CHI3L1-mediated activation of the Akt-signaling in CEC by transfecting the CBM-mutant CHI3L1 vectors in SW480 CECs. Downstream, CHI3L1 enhanced the secretion of IL-8 and TNF alpha in a dose-dependent manner. We previously show that 325 through 339 amino-acids in CBM are crucial for the biological function of CHI3L1. Here we demonstrated that 325th-339th residues of CBM in CHI3L1 is a critical region for the activation of Akt, IL-8 production, and for a specific cellular localization of CHI3L1. In conclusion, CBM region of CHI3L1 is critical in activating Akt signaling in CECs, and the activation may be associated with the development of chronic colitis. (C) 2011 Elsevier Inc. All rights reserved. C1 [Chen, Chun-Chuan; Llado, Victoria; Eurich, Katrin; Tran, Hoa T.; Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA. [Mizoguchi, Emiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Mizoguchi, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, GRJ 702,55 Fruit St, Boston, MA 02114 USA. EM emizoguchi@partners.org FU National Institute of Health [DK80070, DK74454, DK64289, DK43351]; Eli and Edythe L. Broad Medical Foundation; American Gastroenterological Association Foundation FX This work has been supported by National Institute of Health (DK80070, DK74454, DK64289 and DK43351), and grants from the Eli and Edythe L. Broad Medical Foundation and American Gastroenterological Association Foundation to EM. NR 42 TC 34 Z9 36 U1 1 U2 8 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 SEP PY 2011 VL 140 IS 3 BP 268 EP 275 DI 10.1016/j.clim.2011.04.007 PG 8 WC Immunology SC Immunology GA 813UX UT WOS:000294396800010 PM 21546314 ER PT J AU Kerr, CE Shaw, JR Conboy, LA Kelley, JM Jacobson, E Kaptchuk, TJ AF Kerr, Catherine E. Shaw, Jessica R. Conboy, Lisa A. Kelley, John M. Jacobson, Eric Kaptchuk, Ted J. TI Placebo acupuncture as a form of ritual touch healing: A neurophenomenological model SO CONSCIOUSNESS AND COGNITION LA English DT Article DE Placebo acupuncture; Ritual; Touch; Healing; Attentional filtering; Sensory processing; Placebo effect; Phenomenology; Qualitative; Neurophenomenology ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY SOMATOSENSORY CORTEX; IRRITABLE-BOWEL-SYNDROME; CLINICAL-TRIALS; SHAM ACUPUNCTURE; NEEDLE; PHYSIOTHERAPY; STIMULATION; SELECTION; DYNAMICS AB Evidence that placebo acupuncture is an effective treatment for chronic pain presents a puzzle: how do placebo needles appearing to patients to penetrate the body, but instead sitting on the skin's surface in the manner of a tactile stimulus, evoke a healing response? Previous accounts of ritual touch healing in which patients often described enhanced touch sensations (including warmth, tingling or flowing sensations) suggest an embodied healing mechanism. In this qualitative study, we asked a subset of patients in a singleblind randomized trial in irritable bowel syndrome to describe their treatment experiences while undergoing placebo treament. Analysis focused on patients' unprompted descriptions of any enhanced touch sensations (e.g., warmth, tingling) and any significance patients assigned to the sensations. We found in 5/6 cases, patients associated sensations including "warmth" and "tingling" with treatment efficacy. The conclusion offers a "neurophenomenological" account of the placebo effect by considering dynamic effects of attentional filtering on early sensory cortices, possibly underlying the phenomenology of placebo acupuncture. (C) 2011 Elsevier Inc. All rights reserved. C1 [Kerr, Catherine E.; Shaw, Jessica R.; Conboy, Lisa A.; Jacobson, Eric; Kaptchuk, Ted J.] Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA 02215 USA. [Kelley, John M.] Endicott Coll, Beverly, MA USA. [Kelley, John M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02215 USA. RP Kerr, CE (reprint author), Harvard Univ, Sch Med, Osher Res Ctr, Boston, MA 02215 USA. EM catherine_kerr@hms.harvard.edu FU NCCIH NIH HHS [K01 AT003459-02, K01 AT003459-04, R01 AT001414, K24 AT004095, K01AT003459, K01 AT003459-03, K01 AT003459] NR 44 TC 12 Z9 12 U1 1 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8100 J9 CONSCIOUS COGN JI Conscious. Cogn. PD SEP PY 2011 VL 20 IS 3 BP 784 EP 791 DI 10.1016/j.concog.2010.12.009 PG 8 WC Psychology, Experimental SC Psychology GA 815GZ UT WOS:000294515400029 PM 21397519 ER PT J AU Hornsby, BWY Johnson, EE Picou, E AF Hornsby, Benjamin W. Y. Johnson, Earl E. Picou, Erin TI Effects of Degree and Configuration of Hearing Loss on the Contribution of High- and Low-Frequency Speech Information to Bilateral Speech Understanding SO EAR AND HEARING LA English DT Article ID THAN-NORMAL LEVELS; DEAD REGIONS; IMPAIRED LISTENERS; ARTICULATION INDEX; CONSONANT RECOGNITION; WORD RECOGNITION; NOISE; AUDIBILITY; AMPLIFICATION; INTELLIGIBILITY AB Objectives: The purpose of this study was to examine the effects of degree and configuration of hearing loss on the use of, and benefit from, information in amplified high- and low-frequency speech presented in background noise. Design: Sixty-two adults with a wide range of high-and low-frequency sensorineural hearing loss (5 to 115+ dB HL) participated in the study. To examine the contribution of speech information in different frequency regions, speech understanding in noise was assessed in multiple low-and high-pass filter conditions, as well as a band-pass (713 to 3534 Hz) and wideband (143 to 8976 Hz) condition. To increase audibility over a wide frequency range, speech and noise were amplified based on each individual's hearing loss. A stepwise multiple linear regression approach was used to examine the contribution of several factors to (1) absolute performance in each filter condition and (2) the change in performance with the addition of amplified high-and low-frequency speech components. Results: Results from the regression analysis showed that degree of hearing loss was the strongest predictor of absolute performance for low-and high-pass filtered speech materials. In addition, configuration of hearing loss affected both absolute performance for severely low-pass filtered speech and benefit from extending high-frequency (3534 to 8976 Hz) bandwidth. Specifically, individuals with steeply sloping high-frequency losses made better use of low-pass filtered speech information than individuals with similar low-frequency thresholds but less high-frequency loss. In contrast, given similar high-frequency thresholds, individuals with flat hearing losses received more benefit from extending high-frequency bandwidth than individuals with more sloping losses. Conclusions: Consistent with previous work, benefit from speech information in a given frequency region generally decreases as degree of hearing loss in that frequency region increases. However, given a similar degree of loss, the configuration of hearing loss also affects the ability to use speech information in different frequency regions. Except for individuals with steeply sloping high-frequency losses, providing high-frequency amplification (3534 to 8976 Hz) had either a beneficial effect on, or did not significantly degrade, speech understanding. These findings highlight the importance of extended high-frequency amplification for listeners with a wide range of high-frequency hearing losses, when seeking to maximize intelligibility. C1 [Hornsby, Benjamin W. Y.; Picou, Erin] Vanderbilt Univ, Vanderbilt Bill Wilkerson Ctr, Dan Maddox Hearing Aid Res Lab, Dept Hearing & Speech Sci, Nashville, TN 37232 USA. [Johnson, Earl E.] US Dept Vet Affairs, Mountain Home, TN USA. [Johnson, Earl E.] E Tennessee State Univ, Dept Communicat Disorders, Mountain Home, TN USA. RP Hornsby, BWY (reprint author), Vanderbilt Univ, Vanderbilt Bill Wilkerson Ctr, Dan Maddox Hearing Aid Res Lab, Dept Hearing & Speech Sci, Room 8310 Med Ctr E,South Tower,1215 21st Ave S, Nashville, TN 37232 USA. EM ben.hornsby@vanderbilt.edu FU National Institute on Deafness and Other Communication Disorders (National Institutes of Health) [R03 DC006576]; Dan Maddox Hearing Aid Research Foundation FX This work was supported, in part, by Grant R03 DC006576 from the National Institute on Deafness and Other Communication Disorders (National Institutes of Health) and the Dan Maddox Hearing Aid Research Foundation. NR 47 TC 22 Z9 25 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD SEP-OCT PY 2011 VL 32 IS 5 BP 543 EP 555 DI 10.1097/AUD.0b013e31820e5028 PG 13 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 812HI UT WOS:000294281400001 PM 21336138 ER PT J AU Matt, GE Quintana, PJE Destaillats, H Gundel, LA Sleiman, M Singer, BC Jacob, P Benowitz, N Winickoff, JP Rehan, V Talbot, P Schick, S Samet, J Wang, YS Hang, B Martins-Green, M Pankow, JF Hovell, MF AF Matt, Georg E. Quintana, Penelope J. E. Destaillats, Hugo Gundel, Lara A. Sleiman, Mohamad Singer, Brett C. Jacob, Peyton, III Benowitz, Neal Winickoff, Jonathan P. Rehan, Virender Talbot, Prue Schick, Suzaynn Samet, Jonathan Wang, Yinsheng Hang, Bo Martins-Green, Manuela Pankow, James F. Hovell, Melbourne F. TI Thirdhand Tobacco Smoke: Emerging Evidence and Arguments for a Multidisciplinary Research Agenda SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE aggregate exposures; biomarkers; cumulative exposure; exposure; housing; nicotine; policy; secondhand smoke; tobacco smoke ID BASIC ORGANIC POLLUTANT; GAS-PHASE ORGANICS; INDOOR ENVIRONMENTS; EMISSION FACTORS; CARBON-DIOXIDE; EXPOSURE; OZONE; NICOTINE; SURFACES; DUST AB BACKGROUND: There is broad consensus regarding the health impact of tobacco use and secondhand smoke exposure, yet considerable ambiguity exists about the nature and consequences of thirdhand smoke (THS). OBJECTIVES: We introduce definitions of THS and THS exposure and review recent findings about constituents, indoor sorption-desorption dynamics, and transformations of THS; distribution and persistence of THS in residential settings; implications for pathways of exposure; potential clinical significance and health effects; and behavioral and policy issues that affect and are affected by THS. DISCUSSION: Physical and chemical transformations of tobacco smoke pollutants take place over time scales ranging from seconds to months and include the creation of secondary pollutants that in some cases are more toxic (e. g., tobacco-specific nitrosamines). THS persists in real-world residential settings in the air, dust, and surfaces and is associated with elevated levels of nicotine on hands and cotinine in urine of nonsmokers residing in homes previously occupied by smokers. Much still needs to be learned about the chemistry, exposure, toxicology, health risks, and policy implications of THS. CONCLUSION: The existing evidence on THS provides strong support for pursuing a programmatic research agenda to close gaps in our current understanding of the chemistry, exposure, toxicology, and health effects of THS, as well as its behavioral, economic, and sociocultural considerations and consequences. Such a research agenda is necessary to illuminate the role of THS in existing and future tobacco control efforts to decrease smoking initiation and smoking levels, to increase cessation attempts and sustained cessation, and to reduce the cumulative effects of tobacco use on morbidity and mortality. C1 [Matt, Georg E.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. [Quintana, Penelope J. E.; Hovell, Melbourne F.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. [Destaillats, Hugo; Gundel, Lara A.; Sleiman, Mohamad; Singer, Brett C.] Univ Calif Berkeley, Lawrence Berkeley Lab, Indoor Environm Dept, Berkeley, CA 94720 USA. [Jacob, Peyton, III; Benowitz, Neal; Schick, Suzaynn] Univ Calif San Francisco, San Francisco Gen Hosp, Med Ctr, San Francisco, CA 94143 USA. [Winickoff, Jonathan P.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Rehan, Virender] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Talbot, Prue] Univ Calif Riverside, Stem Cell Ctr, Riverside, CA 92521 USA. [Samet, Jonathan] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Hang, Bo] Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Canc & DNA Damage Responses, Berkeley, CA 94720 USA. [Martins-Green, Manuela] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Pankow, James F.] Portland State Univ, Portland, OR 97207 USA. RP Matt, GE (reprint author), San Diego State Univ, Dept Psychol, 5500 Campanile Dr, San Diego, CA 92182 USA. EM gmatt@sciences.sdsu.edu RI Destaillats, Hugo/B-7936-2013 FU California Tobacco Related Disease Research Program; Flight Attendant Medical Research Institute; National Institutes of Health; Flight Attendant Medical Research Institute (FAMRI) FX Parts of the research reported here were supported by the California Tobacco Related Disease Research Program, the Flight Attendant Medical Research Institute, and the National Institutes of Health.; N. Benowitz, M. Hovell, P. Jacob, G. Matt, J. Samet, S. Schick, and J. Winickoff were funded in part by grants from Flight Attendant Medical Research Institute (FAMRI). NR 58 TC 125 Z9 128 U1 4 U2 64 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2011 VL 119 IS 9 BP 1218 EP 1226 DI 10.1289/ehp.1103500 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 814SV UT WOS:000294478400020 PM 21628107 ER PT J AU Chiu, YHM Spiegelman, D Dockery, DW Garshick, E Hammond, SK Smith, TJ Hart, JE Laden, F AF Chiu, Yueh-Hsiu Mathilda Spiegelman, Donna Dockery, Douglas W. Garshick, Eric Hammond, S. Katharine Smith, Thomas J. Hart, Jaime E. Laden, Francine TI Secondhand Smoke Exposure and Inflammatory Markers in Nonsmokers in the Trucking Industry SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cardiovascular disease; CRP; IL-6; inflammatory marker; nonsmoker; occupational health; plasma cotinine; secondhand smoke; sICAM-1; trucking industry ID ENVIRONMENTAL TOBACCO-SMOKE; C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS; CORONARY-HEART-DISEASE; INTERCELLULAR-ADHESION MOLECULE-1; CIGARETTE-SMOKING; SERUM COTININE; ASSOCIATION; METAANALYSES; OCCUPATION AB BACKGROUND: Few studies have directly assessed the association of secondhand smoke (SHS) with cardiovascular disease-related inflammatory markers, and the findings are inconsistent. OBJECTIVES: We assessed the association between SHS exposure and the inflammatory markers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and soluble inter-cellular adhesion molecule-1 (sICAM-1) in 199 non-smoking U. S. trucking industry workers. METHODS: Participants provided blood samples either by mail (blood drawn at local health care provider near home) or at the work site (blood drawn by research staff on-site) and completed a health and work history questionnaire at the time of blood draw. Exposure to SHS was measured by plasma cotinine concentrations. We used multivariate regression analyses to assess the associations between levels of cotinine and inflammatory markers. RESULTS: The median cotinine level was 0.10 ng/mL (interquartile range, 0.04-0.23 ng/mL). The odds ratios of elevated hs-CRP (above highest CRP tertile, 1.5 mg/L) were 2.85 [95% confidence interval (CI), 1.03-7.89] for the high-cotinine group (> 0.215 ng/mL) and 2.80 (95% CI, 1.11-7.10) for the moderate-cotinine group (0.05-0.215 ng/mL), compared with the low-cotinine group (< 0.05 ng/mL), adjusting for age, sex, race, educational level, obesity, previous smoking history, job title, and medical history. Plasma cotinine levels were not associated with IL-6 or sICAM-1. CONCLUSIONS: SHS exposure, as assessed by plasma cotinine, was positively associated with hs-CRP in this group of blue-collar workers. The strength of the association with hs-CRP depended on the cut points selected for analysis. C1 [Chiu, Yueh-Hsiu Mathilda; Dockery, Douglas W.; Smith, Thomas J.; Laden, Francine] Harvard Univ, Sch Publ Hlth, EER Program, Dept Environm Hlth, Boston, MA 02215 USA. [Chiu, Yueh-Hsiu Mathilda; Garshick, Eric; Hart, Jaime E.; Laden, Francine] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Chiu, Yueh-Hsiu Mathilda; Garshick, Eric; Hart, Jaime E.; Laden, Francine] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Spiegelman, Donna; Dockery, Douglas W.; Hart, Jaime E.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Garshick, Eric] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA. [Hammond, S. Katharine] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Chiu, YHM (reprint author), Harvard Univ, Sch Publ Hlth, EER Program, Dept Environm Hlth, 401 Pk Dr,Landmark 4th Floor, Boston, MA 02215 USA. EM yhchiu@hsph.harvard.edu FU Flight Attendant Medical Research Institute (FAMRI); National Institutes of Health/National Institute of Environmental Health Sciences [R21 ES013726]; Harvard-National Institute for Occupational Safety and Health Education and Research Center [T42 OH 008416-03]; American Heart Association [0815689D] FX This study was supported by the Flight Attendant Medical Research Institute (FAMRI; F.L.); National Institutes of Health/National Institute of Environmental Health Sciences grant R21 ES013726 (E.G.); Harvard-National Institute for Occupational Safety and Health Education and Research Center grant T42 OH 008416-03 (F.L., Y.-H.M.C); and American Heart Association award 0815689D Y.-H.M.C). NR 43 TC 14 Z9 14 U1 2 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2011 VL 119 IS 9 BP 1294 EP 1300 DI 10.1289/ehp.1003199 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 814SV UT WOS:000294478400031 PM 21628108 ER PT J AU Korrick, SA Lee, MM Williams, PL Sergeyev, O Burns, JS Patterson, DG Turner, WE Needham, LL Altshul, L Revich, B Hauser, R AF Korrick, Susan A. Lee, Mary M. Williams, Paige L. Sergeyev, Oleg Burns, Jane S. Patterson, Donald G., Jr. Turner, Wayman E. Needham, Larry L. Altshul, Larisa Revich, Boris Hauser, Russ TI Dioxin Exposure and Age of Pubertal Onset among Russian Boys SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE children; dioxins; furans; growth; PCBs; polychlorinated biphenyls; pubertal stage; puberty; testicular volume ID SECONDARY SEXUAL CHARACTERISTICS; BLOOD LEAD LEVELS; NUTRITION EXAMINATION SURVEY; TOXIC EQUIVALENCY FACTORS; POLYCHLORINATED-BIPHENYLS; HUMAN-SERUM; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; ORGANOCHLORINE PESTICIDES; ENDOCRINE DISRUPTORS; LACTATIONAL EXPOSURE AB BACKGROUND: Animal data demonstrate associations of dioxin, furan, and polychlorinated biphenyl (PCB) exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations. OBJECTIVES: We investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region. METHODS: Between 2003 and 2005, 499 boys 8-9 years of age were enrolled in a longitudinal study in Chapaevsk, Russia. Pubertal onset [stage 2 or higher for genitalia (G2+) or testicular volume (TV) > 3 mL] was assessed annually between ages 8 and 12 years. Serum levels at enrollment were analyzed by the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. We used Cox proportional hazards models to assess age at pubertal onset as a function of exposure adjusted for potential confounders. We conducted sensitivity analyses excluding boys with pubertal onset at enrollment. RESULTS: The median (range) total serum TEQ concentration was 21 (4-175) pg/g lipid, approximately three times higher than values in European children. At enrollment, boys were generally healthy and normal weight (mean body mass index, 15.9 kg/m(2)), with 30% having entered puberty by G2+ and 14% by TV criteria. Higher dioxin TEQs were associated with later pubertal onset by TV (hazard ratio = 0.68, 95% confidence interval, 0.49-0.95 for the highest compared with the lowest quartile). Similar associations were observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin concentrations for TV but not G2+. Results were robust to sensitivity analyses. CONCLUSIONS: Findings support an association of higher peripubertal serum dioxin TEQs and concentrations with later male pubertal onset reflected in delayed testicular maturation. C1 [Korrick, Susan A.; Turner, Wayman E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. [Korrick, Susan A.; Burns, Jane S.; Altshul, Larisa; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Lee, Mary M.] Univ Massachusetts, Sch Med, Dept Pediat, Pediat Endocrine Div, Worcester, MA USA. [Lee, Mary M.] Univ Massachusetts, Sch Med, Dept Cell Biol, Pediat Endocrine Div, Worcester, MA 01655 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Sergeyev, Oleg] Samara State Med Univ, Dept Phys Educ & Hlth, Samara, Russia. [Sergeyev, Oleg] Chapaevsk Med Assoc, Chapaevsk, Russia. [Patterson, Donald G., Jr.; Needham, Larry L.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Patterson, Donald G., Jr.] Axys Analyt Solut, Sidney, BC, Canada. [Patterson, Donald G., Jr.] FMS, Boston, MA USA. [Patterson, Donald G., Jr.] Exponent Inc, Maynard, MA USA. [Patterson, Donald G., Jr.] EnviroSolut Consulting Inc, Auburn, GA USA. [Turner, Wayman E.] Ctr Dis Control & Prevent Fdn, Atlanta, GA USA. [Altshul, Larisa] Environm Hlth & Engn Inc, Needham, MA USA. [Revich, Boris] Russian Acad Sci, Ctr Demog & Human Ecol, Moscow, Russia. [Revich, Boris] Russian Acad Sci, Inst Forecasting, Moscow, Russia. [Hauser, Russ] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv,Androl Lab, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Sch Med, Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02115 USA. RP Korrick, SA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM susan.korrick@channing.harvard.edu RI Sergeyev, Oleg/H-8854-2013; OI Sergeyev, Oleg/0000-0002-5745-3348; Lee, Mary/0000-0002-7204-4884 FU U.S. Environmental Protection Agency (EPA) [R82943701]; National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) [ES014370, ES000002] FX This work was funded by U.S. Environmental Protection Agency (EPA) grant R82943701 and National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) grants ES014370 and ES000002. M.M.L. is a member of the University of Massachusetts Diabetes and Endocrine Research Center (DK32520). NR 50 TC 18 Z9 18 U1 5 U2 16 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2011 VL 119 IS 9 BP 1339 EP 1344 DI 10.1289/ehp.1003102 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 814SV UT WOS:000294478400038 PM 21527364 ER PT J AU Hill-Burns, EM Hamza, TH Zabetian, CP Factor, SA Payami, H AF Hill-Burns, E. M. Hamza, T. H. Zabetian, C. P. Factor, S. A. Payami, H. TI An attempt to replicate interaction between coffee and CYP1A2 gene in connection to Parkinson's disease SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Letter DE coffee; CYP1A2; Parkinson's disease ID CAFFEINE; SMOKING; RISK C1 [Hill-Burns, E. M.; Hamza, T. H.; Payami, H.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Zabetian, C. P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Zabetian, C. P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Factor, S. A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Payami, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. EM hpayami@wadsworth.org OI Zabetian, Cyrus/0000-0002-7739-4306 FU NINDS NIH HHS [R01 NS036960] NR 6 TC 3 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2011 VL 18 IS 9 BP E107 EP E108 DI 10.1111/j.1468-1331.2011.03464.x PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 813DO UT WOS:000294347200001 PM 21834891 ER PT J AU Tang, HB Lee, M Budak, MT Pietras, N Hittinger, S Vu, M Khuong, A Hoang, CD Hussain, SNA Levine, S Shrager, JB AF Tang, Huibin Lee, Myung Budak, Murat T. Pietras, Nicole Hittinger, Scott Vu, Michael Khuong, Andy Hoang, Chuong D. Hussain, Sabah N. A. Levine, Sanford Shrager, Joseph B. TI Intrinsic apoptosis in mechanically ventilated human diaphragm: linkage to a novel Fos/FoxO1/Stat3-Bim axis SO FASEB JOURNAL LA English DT Article DE oxidative stress; skeletal muscle; dysfunction; atrophy; respiratory muscle ID MUSCLE PROTEIN-DEGRADATION; REGIONAL WEANING CENTER; CONTRACTILE PROPERTIES; CATABOLIC CONDITIONS; OXIDATIVE STRESS; SKELETAL-MUSCLE; GENE-EXPRESSION; RAT DIAPHRAGM; CARE-UNIT; DYSFUNCTION AB Mechanical ventilation (MV) is a life-saving measure in many critically ill patients. However, prolonged MV results in diaphragm dysfunction that contributes to the frequent difficulty in weaning patients from the ventilator. The molecular mechanisms underlying ventilator-induced diaphragm dysfunction (VIDD) remain poorly understood. We report here that MV induces myonuclear DNA fragmentation (3-fold increase; P<0.01) and selective activation of caspase 9 (P<0.05) and Bcl2-interacting mediator of cell death (Bim; 2- to 7-fold increase; P<0.05) in human diaphragm. MV also statistically significantly down-regulates mitochondrial gene expression and induces oxidative stress. In cultured muscle cells, we show that oxidative stress activates each of the catabolic pathways thought to underlie VIDD: apoptotic (P<0.05), proteasomal (P<0.05), and autophagic (P<0.01). Further, silencing Bim expression blocks (P<0.05) oxidative stress-induced apoptosis. Overlapping the gene expression profiles of MV human diaphragm and H(2)O(2)-treated muscle cells, we identify Fos, FoxO1, and Stat3 as regulators of Bim expression as well as of expression of the catabolic markers atrogin and LC3. We thus identify a novel Fos/FoxO1/Stat3-Bim intrinsic apoptotic pathway and establish the centrality of oxidative stress in the development of VIDD. This information may help in the design of specific drugs to prevent this condition.-Tang, H., Lee, M., Budak, M. T., Pietras, N., Hittinger, S., Vu, M., Khuong, A., Hoang, C. D., Hussain, S. N. A., Levine, S., Shrager, J. B. Intrinsic apoptosis in mechanically ventilated human diaphragm: linkage to a novel Fos/FoxO1/Stat3-Bim axis. FASEB J. 25, 2921-2936 (2011). www.fasebj.org C1 [Tang, Huibin; Lee, Myung; Pietras, Nicole; Hittinger, Scott; Vu, Michael; Khuong, Andy; Hoang, Chuong D.; Shrager, Joseph B.] Stanford Univ, Sch Med, Dept Cardiothorac Surg, Div Thorac Surg, Stanford, CA 94305 USA. [Tang, Huibin; Lee, Myung; Pietras, Nicole; Hittinger, Scott; Vu, Michael; Khuong, Andy; Hoang, Chuong D.; Shrager, Joseph B.] Vet Affairs Palo Alto Healthcare Syst, Palo Alto, CA USA. [Budak, Murat T.; Levine, Sanford] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. [Budak, Murat T.; Levine, Sanford] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Hussain, Sabah N. A.] McGill Univ, Royal Victoria Hosp, Div Resp, Montreal, PQ H3A 1A1, Canada. [Hussain, Sabah N. A.] McGill Univ, Royal Victoria Hosp, Crit Care Div, Montreal, PQ H3A 1A1, Canada. RP Shrager, JB (reprint author), Stanford Univ, Sch Med, Dept Cardiothorac Surg, Div Thorac Surg, 300 Pasteur Dr, Stanford, CA 94305 USA. EM shrager@stanford.edu RI Budak, Murat/I-8358-2013 OI Budak, Murat/0000-0002-5059-9651 FU Veterans Affairs; U.S. National Institutes of Health [HL078834] FX The authors thank Kevin Hoang (summer student at University of California, San Diego, CA, USA) and Donna Minagawa (Stanford University) for technical assistance and Xiaohua Zhang (Stanford University) for assistance in bioinformatics analysis. This research was supported by a Veterans Affairs merit review grant awarded to J.B.S. and also in part by U.S. National Institutes of Health grant HL078834. The authors declare that they have no financial relationship with a commercial entity. NR 67 TC 29 Z9 29 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2011 VL 25 IS 9 BP 2921 EP 2936 DI 10.1096/fj.11-183798 PG 16 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 814GD UT WOS:000294435200008 PM 21597002 ER PT J AU Jegot, G Derache, C Castella, S Lahouassa, H Pitois, E Jourdan, ML Remold-O'Donnell, E Kellenberger, C Gauthier, F Korkmaz, B AF Jegot, Gwenhael Derache, Chrystelle Castella, Sandrine Lahouassa, Hichem Pitois, Elodie Jourdan, Marie Lise Remold-O'Donnell, Eileen Kellenberger, Christine Gauthier, Francis Korkmaz, Brice TI A substrate-based approach to convert SerpinB1 into a specific inhibitor of proteinase 3, the Wegener's granulomatosis autoantigen SO FASEB JOURNAL LA English DT Article DE neutrophil; serine protease; drug design ID HUMAN POLYMORPHONUCLEAR NEUTROPHILS; CATHEPSIN-G; ELASTASE INHIBITOR; ALPHA-1-ANTITRYPSIN DEFICIENCY; ALPHA-1-PROTEASE INHIBITOR; SERINE PROTEINASES; CRYSTAL-STRUCTURE; CYSTIC-FIBROSIS; IN-VIVO; SURFACE AB The physiological and pathological functions of proteinase 3 (PR3) are not well understood due to its close similarity to human neutrophil elastase (HNE) and the lack of a specific inhibitor. Based on structural analysis of the active sites of PR3 and HNE, we generated mutants derived from the polyvalent inhibitor SerpinB1 (monocyte/neutrophil elastase inhibitor) that specifically inhibit PR3 and that differ from wt-SerpinB1 by only 3 or 4 residues in the reactive center loop. The rate constant of association between the best SerpinB1 mutant and PR3 is 1.4 x 10(7) M(-1) . s(-1), which is similar to 100-fold higher than that observed with wt-SerpinB1 and compares with that of alpha 1-protease inhibitor (alpha 1-PI) toward HNE. SerpinB1(S/DAR) is cleaved by HNE, but due to differences in rate, inhibition of PR3 by SerpinB1(S/DAR) is only minimally affected by the presence of HNE even when the latter is in excess. SerpinB1(S/DAR) inhibits soluble PR3 and also membrane-bound PR3 at the surface of activated neutrophils. Moreover, SerpinB1(S/DAR) clears induced PR3 from the surface of activated neutrophils. Overall, these specific inhibitors of PR3 will be valuable for defining biological functions of the protease and may prove useful as therapeutics for PR3-related inflammatory diseases, such as Wegener's granulomatosis.-Jegot, G., Derache, C., Castella, S., Lahouassa, H., Pitois, E., Jourdan, M. L., Remold-O'Donnell, E., Kellenberger, C., Gauthier, F., Korkmaz, B. A substrate-based approach to convert SerpinB1 into a specific inhibitor of proteinase 3, the Wegener's granulomatosis autoantigen. FASEB J. 25, 3019-3031 (2011). www.fasebj.org C1 [Korkmaz, Brice] Univ Tours, Fac Med, INSERM, U618, F-37032 Tours, France. [Derache, Chrystelle] CNRS, Ctr Biophys Mol, Orleans, France. [Jourdan, Marie Lise] Ctr Hosp Reg Univ, Tours, France. [Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Kellenberger, Christine] CNRS, UMR, Marseille, France. RP Korkmaz, B (reprint author), Univ Tours, Fac Med, INSERM, U618, F-37032 Tours, France. EM brice.korkmaz@inserm.fr OI KORKMAZ, BRICE/0000-0002-5159-8706 FU Region Centre; Fonds Europeen de Developpement Regional FX This work was supported by Region Centre and the Fonds Europeen de Developpement Regional (Projet INFINHI). B. K. acknowledges the Fondation Pour La Recherche Medicale (FRM). The authors thank Dr. Dieter Jenne (Max Planck Institute of Neurobiology, Martinsried, Germany) for sending proteinase 3 plasmid, Dr. Michele Brillard-Bourdet for sequence analyses, Dr. Martine Cadene (Centre de Biophysique Moleculaire, Orleans, France) for performing MALDI-TOF mass spectrometry analysis, and Dr. Herve Watier and Dr. Danielle Degenne (Centre Hospitalier Regional Universitaire, Tours, France) for providing WG blood samples. The authors appreciatively acknowledge contributions of Dr. Nicolas Guyot, Marine Sigismeau, and Lise Vanderlynden to early phases of this work. NR 59 TC 8 Z9 9 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2011 VL 25 IS 9 BP 3019 EP 3031 DI 10.1096/fj.10-176552 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 814GD UT WOS:000294435200017 PM 21670065 ER PT J AU Seriwatanachai, D Densmore, MJ Sato, T Correa, D Neff, L Baron, R Lanske, B AF Seriwatanachai, Dutmanee Densmore, Michael J. Sato, Tadatoshi Correa, Diego Neff, Lynn Baron, Roland Lanske, Beate TI Deletion of Zfp521 rescues the growth plate phenotype in a mouse model of Jansen metaphyseal chondrodysplasia SO FASEB JOURNAL LA English DT Article DE chondrocyte; endochondral bone formation; PTHrP; JMC; zinc finger protein ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-FORMATION; PARATHYROID-HORMONE; PTH/PTHRP RECEPTOR; SKELETAL DEVELOPMENT; INDIAN HEDGEHOG; IN-VITRO; CHONDROCYTE MATURATION; TARGETED EXPRESSION; MICE AB Jansen metaphyseal chondrodysplasia (JMC) is caused by a constitutively activating mutation of the parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor (PTHR1) and is characterized by widening of the metaphyses, reduction of long bone length, and short stature. A transgenic mouse expressing this mutation under the collagen alpha 1(II) promoter has been generated to investigate the mechanisms responsible for this chondrodysplasia. We recently identified zinc finger protein 521 (Zfp521) as a downstream target gene of PTHrP signaling. Interestingly, loss of Zfp521 from chondrocytes leads to reduced cell proliferation and increased differentiation in the growth plate. Thus, we hypothesized that specifically ablating Zfp521 from Jansen chondrocytes could sufficiently rescue the chondrodysplasia phenotype. Our results show that Zfp521 expression is up-regulated in Jansen mouse growth plate chondrocytes and that PTHR1 is required for Zfp521 expression. Its ablation from Jansen chondrocytes restored normal cell differentiation, thus initiating chondrocyte apoptosis at the chondro-osseous junction, leading to partial rescue of endochondral bone formation shown by proper bone length. This study provides the first genetic evidence that Zfp521 is required downstream of PTHR1 signaling to act on chondrocyte proliferation, differentiation, and cell death.-Seriwatanachai, D., Densmore, M. J., Sato, T., Correa, D., Neff, L., Baron, R., Lanske, B. Deletion of Zfp521 rescues the growth plate phenotype in a mouse model of Jansen metaphyseal chondrodysplasia. FASEB J. 25, 3057-3067 (2011). www.fasebj.org C1 [Seriwatanachai, Dutmanee; Densmore, Michael J.; Sato, Tadatoshi; Lanske, Beate] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Correa, Diego; Neff, Lynn; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Baron, Roland] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. RP Lanske, B (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, Res & Educ Bldg,Rm 303,188 Longwood Ave, Boston, MA 02115 USA. EM beate_lanske@hsdm.harvard.edu FU U.S. National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR050560, AR057769] FX The authors thank Drs. Neal G. Copeland, Soren Warming, Riku Kiviranta, and Yukiko Maeda for helpful suggestions. This work was supported by U.S. National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases grants AR050560 (B. L.) and AR057769 (R. B.). NR 27 TC 12 Z9 12 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2011 VL 25 IS 9 BP 3057 EP 3067 DI 10.1096/fj.11-183277 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 814GD UT WOS:000294435200020 PM 21642473 ER PT J AU Archer, DF Shifren, JL Cheng, RFJ Bao, W Guico-Pabia, CJ AF Archer, D. F. Shifren, J. L. Cheng, R. -F. J. Bao, W. Guico-Pabia, C. J. TI TOLERABILITY OF DESVENLAFAXINE 100 MG IN WOMEN WITH VASOMOTOR SYMPTOMS (VMS) ASSOCIATED WITH MENOPAUSE: A POOLED ANALYSIS OF 5 TRIALS SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pfizer Inc, Collegeville, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S4 EP S5 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700014 ER PT J AU Chavarro, JE Attaman, JA Toth, TL Ford, JB Keller, M Hauser, R AF Chavarro, J. E. Attaman, J. A. Toth, T. L. Ford, J. B. Keller, M. Hauser, R. TI INTAKE OF TRANS FATTY ACIDS AND SEMEN QUALITY AMONG MEN ATTENDING A FERTILITY CLINIC SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, MGH Fertil Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S14 EP S15 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700049 ER PT J AU Colaci, DS Gaskins, AJ Toth, TL Petrozza, J Chavarro, JE AF Colaci, D. S. Gaskins, A. J. Toth, T. L. Petrozza, J. Chavarro, J. E. TI ANTIOXIDANTS INTAKE AND SEMEN QUALITY IN MEN ATTENDING A FERTILITY CLINIC SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Fertil Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S165 EP S165 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700562 ER PT J AU Doyle, JO Wright, DL Toth, TL Styer, AK AF Doyle, J. O. Wright, D. L. Toth, T. L. Styer, A. K. TI OVERALL DAY FIVE EMBRYO COHORT IS ASSOCIATED WITH LIVEBIRTH SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 [Doyle, J. O.; Wright, D. L.; Toth, T. L.; Styer, A. K.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S66 EP S66 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700222 ER PT J AU Doyle, JO Imudia, AN Veiga, C Wright, DL Styer, AK Toth, TL AF Doyle, J. O. Imudia, A. N. Veiga, C. Wright, D. L. Styer, A. K. Toth, T. L. TI OBSTETRICAL OUTCOMES OF SINGLETON AND MULTIPLE GESTATATION IVF PREGNANCIES CONCEIVED FOLLOWING TRANSFER OF CRYOPRESERVED AND FRESH EMBRYOS SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 [Doyle, J. O.; Imudia, A. N.; Veiga, C.; Wright, D. L.; Styer, A. K.; Toth, T. L.] Massachusetts Gen Hosp, Fertil Ctr, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S28 EP S29 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700096 ER PT J AU Ehrlich, S Williams, PL Missmer, SA Berry, KF Petrozza, J Hauser, R AF Ehrlich, S. Williams, P. L. Missmer, S. A. Berry, K. F. Petrozza, J. Hauser, R. TI URINARY BISPHENOL A AND IMPLANTATION FAILURE AMONG WOMEN UNDERGOING IN VITRO FERTILIZATION SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Ctr Infertil & Reprod Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Fertil Ctr, Boston, MA 02114 USA. RI Ehrlich , Shelley/L-6991-2015 NR 0 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S6 EP S7 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700021 ER PT J AU Imudia, AN McLellan, ST Veiga, C Wright, DL Toth, TL Styer, AK AF Imudia, A. N. McLellan, S. T. Veiga, C. Wright, D. L. Toth, T. L. Styer, A. K. TI IVF OUTCOMES FOLLOWING GNRH AGONIST FLARE AND GNRH ANTAGONIST STIMULATION PROTOCOLS IN YOUNG LOW RESPONDERS UNDERGOING THEIR FIRST IVF CYCLE SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 [Imudia, A. N.; McLellan, S. T.; Veiga, C.; Wright, D. L.; Toth, T. L.; Styer, A. K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Dept Obstet & Gynecol,Fertil Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S263 EP S263 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452701128 ER PT J AU Imudia, AN Awonuga, AO Doyle, JO Wright, DL Toth, TL Styer, AK AF Imudia, A. N. Awonuga, A. O. Doyle, J. O. Wright, D. L. Toth, T. L. Styer, A. K. TI THE IMPACT OF PEAK SERUM ESTRADIOL LEVEL DURING CONTROLLED OVARIAN HYPERSTIMULATION ON ADVERSE OBSTETRICAL OUTCOMES IN SINGLETON PREGNANCY CONCEIVED FOLLOWING IVF-ET SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Fertil Ctr,Vincent Dept Obstet & Gynecol, Boston, MA USA. Wayne State Univ, Sch Med, Div Reprod Endocrinol & Infertil, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S189 EP S189 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700647 ER PT J AU Imudia, AN Woods, DC White, YAR Tilly, JL AF Imudia, A. N. Woods, D. C. White, Y. A. R. Tilly, J. L. TI DYNAMIC CHANGES IN OOGONIAL STEM CELL NUMBERS IN MOUSE OVARIES DURING THE REPRODUCTIVE CYCLE AND FOLLOWING HEMI-OVARIECTOMY SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 [Imudia, A. N.; Woods, D. C.; White, Y. A. R.; Tilly, J. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S103 EP S103 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700346 ER PT J AU Kagan, L Psaros, C Alert, MD Styer, AK Shifren, JL Park, ER AF Kagan, L. Psaros, C. Alert, M. D. Styer, A. K. Shifren, J. L. Park, E. R. TI IMPROVING RESILIENCE AMONG INFERTILE WOMEN: A PILOT STUDY SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Fertil Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S151 EP S151 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700517 ER PT J AU Lee, HJ Selesniemi, K Doyle, JO Toth, TL AF Lee, H. J. Selesniemi, K. Doyle, J. O. Toth, T. L. TI EFFECT OF VITRIFICATION ON MITOCHONDRIAL DISTRIBUTION AND ATP CONCENTRATION DURING OOCYTE MATURATION SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 [Lee, H. J.; Selesniemi, K.; Doyle, J. O.; Toth, T. L.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S237 EP S238 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452701047 ER PT J AU Sabatini, ME Smith, KW Ford, J Ehrlich, SR Toth, TL Hauser, R AF Sabatini, M. E. Smith, K. W. Ford, J. Ehrlich, S. R. Toth, T. L. Hauser, R. TI URINARY PARABEN CONCENTRATIONS AND IN VITRO FERTILIZATION (IVF) OUTCOMES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S154 EP S154 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700527 ER PT J AU Smith, KW Dimitriadis, I Ehrlich, S Ford, J Berry, KF Souter, I AF Smith, K. W. Dimitriadis, I. Ehrlich, S. Ford, J. Berry, K. F. Souter, I. TI THE ASSOCIATION OF URINARY PARABEN CONCENTRATIONS WITH MEASURES OF OVARIAN RESERVE AMONG PATIENTS FROM A FERTILITY CENTER SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Ehrlich , Shelley/L-6991-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S197 EP S197 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700672 ER PT J AU Souter, I Smith, KW Dimitriadis, I Keller, MG Petrozza, JC Hauser, R AF Souter, I. Smith, K. W. Dimitriadis, I. Keller, M. G. Petrozza, J. C. Hauser, R. TI THE ASSOCIATION OF URINARY PHTHALATE MONOESTER CONCENTRATIONS WITH MEASURES OF OVARIAN RESERVE AMONG PATIENTS UNDERGOING FERTILITY TREATMENTS SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Obstet Gynecol Reprod Endocrinol & Infertil Div, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S5 EP S5 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700017 ER PT J AU White, RAR Woods, DC Takai, Y Ishihara, O Seki, H Tilly, JL AF White, R. A. R. Woods, D. C. Takai, Y. Ishihara, O. Seki, H. Tilly, J. L. TI ISOLATION OF MITOTICALLY-ACTIVE GERM CELLS FROM ADULT HUMAN OVARIES: IN-VITRO PROPAGATION AND GENERATION OF IMMATURE OOCYTES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA USA. Saitama Med Sch, Saitama Med Ctr, Dept Obstet & Gynecol, Kawagoe, Saitama, Japan. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S169 EP S170 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700578 ER PT J AU Wright, DL Smith, KW Ehrlich, S Berry, K Toth, TL Hauser, R AF Wright, D. L. Smith, K. W. Ehrlich, S. Berry, K. Toth, T. L. Hauser, R. TI MATERNAL HAIR MERCURY LEVELS AND EARLY IN VITRO FERTILIZATION (IVF) OUTCOMES SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 15-19, 2011 CL Orlando, FL SP Amer Soc Reprod Med C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Div Reprod Med & IVF, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Ctr Infertil & Reprod Surg, Boston, MA 02115 USA. RI Ehrlich , Shelley/L-6991-2015 NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2011 VL 96 IS 3 SU 1 BP S7 EP S7 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 814KZ UT WOS:000294452700022 ER PT J AU Hoefs, JC Shiffman, ML Goodman, ZD Kleiner, DE Dienstag, JL Stoddard, AM AF Hoefs, John C. Shiffman, Mitchell L. Goodman, Zachary D. Kleiner, David E. Dienstag, Jules L. Stoddard, Anne M. CA HALT-C Trial Grp TI Rate of Progression of Hepatic Fibrosis in Patients With Chronic Hepatitis C: Results From the HALT-C Trial SO GASTROENTEROLOGY LA English DT Article DE Rate of Fibrosis Progression; Hepatitis C; Liver Biopsy Fibrosis; Ishak Score ID CHRONIC VIRAL-HEPATITIS; LIVER-BIOPSY; SAMPLING VARIABILITY; NATURAL-HISTORY; VIRUS-INFECTION; CLASSIFICATION; PEGINTERFERON; CIRRHOSIS; THERAPY; DISEASE AB BACKGROUND & AIMS: The gradual accumulation of hepatic fibrosis in chronic liver disease results in clinical complications. The rate of hepatic fibrosis score progression (RFSP) in predicting clinical outcomes was assessed by extending the 4-year Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial to include preenrollment liver biopsies. METHODS: The RFSP was calculated from the linear regression slope of Ishak fibrosis score vs time in 457 patients with liver biopsies (>= 10-mm length) prior to the HALT-C Trial (575 biopsies) plus 1101 on-study biopsies (total 1676 biopsies). Individual slopes were calculated if duration from first to last biopsy was > 4 years. RESULTS: The RFSP as average fibrosis score vs average time in intervals (0 - 3 and > 3 years prestudy, screening, month 24 and 48 on-study) in 455 patients in cohorts of baseline Ishak score ranged from 0.005 with Ishak score 2 to 0.124 with Ishak 6. The RFSP in individual patients (-0.35 to +0.97 Ishak units/year) had a mean of 0.12 +/- 0.23 in 344 patients with prestudy and on-study biopsies (group A) and only 0.17 +/- 0.22 in 169 with prestudy and screening biopsies (group B). Group A patients with RFSP slope >= 0.2 (95 patients, 27.6%) had higher 7-year cumulative rates of non-hepatocellular carcinoma outcomes (46% vs 8%, respectively) and with a hepatocellular carcinoma (10% vs 3%, respectively) than RFSP slope < 02 (249 patients, 72.4%) (P < .0001). RFSP and screening Ishak score correlated independently (P < .0001) with clinical outcomes in multivariate analysis. CONCLUSIONS: Rapid RFSP (> 0.2), which occurred in 26.7% of HALT-C Trial patients, correlated strongly with clinical outcomes. C1 [Hoefs, John C.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Richmond, VA USA. [Goodman, Zachary D.] Inova Fairfax Hosp, Ctr Liver Dis, Falls Church, VA USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA. RP Hoefs, JC (reprint author), Univ Calif Irvine, Med Ctr, 333 Manchester Dr, Orange, CA 92828 USA. EM jchoefs@uci.edu OI Kleiner, David/0000-0003-3442-4453 FU NIH, National Cancer Institute FX Supported in part by the Intramural Research Program of the NIH, National Cancer Institute. NR 32 TC 14 Z9 15 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2011 VL 141 IS 3 BP 900 EP U629 DI 10.1053/j.gastro.2011.06.007 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 812HG UT WOS:000294281200030 PM 21699796 ER PT J AU Yang, KL Moldovan, GL Vinciguerra, P Murai, J Takeda, S D'Andrea, AD AF Yang, Kailin Moldovan, George-Lucian Vinciguerra, Patrizia Murai, Junko Takeda, Shunichi D'Andrea, Alan D. TI Regulation of the Fanconi anemia pathway by a SUMO-like delivery network SO GENES & DEVELOPMENT LA English DT Article DE Fanconi anemia; deubiquitinating enzymes; PCNA; SUMO-like domains ID CROSS-LINK REPAIR; STRAND BREAK REPAIR; DNA-POLYMERASE-ETA; HOMOLOGOUS RECOMBINATION; DEUBIQUITINATING ENZYMES; MONOUBIQUITINATED PCNA; TRANSLESION SYNTHESIS; GENOMIC STABILITY; VERTEBRATE CELLS; UBIQUITIN AB The USP1/UAF1 complex deubiquitinates the Fanconi anemia protein FANCD2, thereby promoting homologous recombination and DNA cross-link repair. How USP1/UAF1 is targeted to the FANCD2/FANCI heterodimer has remained unknown. Here we show that UAF1 contains a tandem repeat of SUMO-like domains in its C terminus (SLD1 and SLD2). SLD2 binds directly to a SUMO-like domain-interacting motif (SIM) on FANCI. Deletion of the SLD2 sequence of UAF1 or mutation of the SIM on FANCI disrupts UAF1/FANCI binding and inhibits FANCD2 deubiquitination and DNA repair. The USP1/UAF1 complex also deubiquitinates PCNA-Ub, and deubiquitination requires the PCNA-binding protein hELG1. The SLD2 sequence of UAF1 binds to a SIM on hELG1, thus targeting the USP1/UAF1 complex to its PCNA-Ub substrate. We propose that the regulated targeting of USP1/UAF1 to its DNA repair substrates, FANCD2-Ub and PCNA-Ub, by SLD-SIM interactions coordinates homologous recombination and translesion DNA synthesis. C1 [Yang, Kailin; Moldovan, George-Lucian; Vinciguerra, Patrizia; D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Yang, Kailin] Harvard Univ, Sch Med, Leder Human Biol Program, Biol & Biomed Sci Program, Boston, MA 02115 USA. [Murai, Junko; Takeda, Shunichi] Kyoto Univ, Dept Radiat Genet, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan. RP D'Andrea, AD (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu RI Yang, Kailin/D-7966-2013; Yang, Kailin/L-2205-2013; OI Yang, Kailin/0000-0001-5968-6738; George-Lucian, Moldovan/0000-0003-3825-149X FU International Human Frontier Science Program Organization; Swiss Foundation for grants in biology and medicine; Swiss National Science Foundation [PASMA3-119584]; TOYOBO Biotechnology Foundation; NIH [R01DK43889, R01HL52725, P01CA092584] FX We thank Minoru Takata for chicken anti-FANCD2 antibody, David Livingston for anti-PALB2 antibody, Kyungjae Myung for anti-hELG1 antibody, David Schild for anti-RAD51AP1 antibody, and Ivan Dikic for cDNAs of Pias1, GST-SUMO1, GST-SUMO2, and GST-SUMO3. We thank Kay Hofmann, Fernando Bazan, Jeff Perry, John Tainer, David Pellman, Daniel Finley, Lee Zou, Johannes Walter, Geoffrey Shapiro, and members of the D'Andrea laboratory for helpful discussions. K.Y. is a Harvard University Presidential Scholar. G. L. M. is supported by a post-doctoral fellowship from the International Human Frontier Science Program Organization. P. V. was supported by a fellowship from the Swiss Foundation for grants in biology and medicine, and by Swiss National Science Foundation grant PASMA3-119584. J.M. is funded by long-term research grants from the TOYOBO Biotechnology Foundation. This work was supported by NIH grants R01DK43889, R01HL52725, P01CA092584 to A.D.D. NR 51 TC 46 Z9 48 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 2011 VL 25 IS 17 BP 1847 EP 1858 DI 10.1101/gad.17020911 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 815UO UT WOS:000294555500009 PM 21896657 ER PT J AU Roark, B Mitchell, M Hosom, JP Hollingshead, K Kaye, J AF Roark, Brian Mitchell, Margaret Hosom, John-Paul Hollingshead, Kristy Kaye, Jeffrey TI Spoken Language Derived Measures for Detecting Mild Cognitive Impairment SO IEEE TRANSACTIONS ON AUDIO SPEECH AND LANGUAGE PROCESSING LA English DT Article DE Forced alignment; linguistic complexity; mild cognitive impairment (MCI); parsing; spoken language understanding ID ALZHEIMERS-DISEASE; COMPLEXITY; SPEECH; SYNTAX AB Spoken responses produced by subjects during neuropsychological exams can provide diagnostic markers beyond exam performance. In particular, characteristics of the spoken language itself can discriminate between subject groups. We present results on the utility of such markers in discriminating between healthy elderly subjects and subjects with mild cognitive impairment (MCI). Given the audio and transcript of a spoken narrative recall task, a range of markers are automatically derived. These markers include speech features such as pause frequency and duration, and many linguistic complexity measures. We examine measures calculated from manually annotated time alignments (of the transcript with the audio) and syntactic parse trees, as well as the same measures calculated from automatic (forced) time alignments and automatic parses. We show statistically significant differences between clinical subject groups for a number of measures. These differences are largely preserved with automation. We then present classification results, and demonstrate a statistically significant improvement in the area under the ROC curve (AUC) when using automatic spoken language derived features in addition to the neuropsychological test scores. Our results indicate that using multiple, complementary measures can aid in automatic detection of MCI. C1 [Roark, Brian; Hosom, John-Paul] Oregon Hlth & Sci Univ, Dept Biomed Engn, Ctr Spoken Language Understanding, Portland, OR 97239 USA. [Mitchell, Margaret] Univ Aberdeen, Dept Comp Sci, Aberdeen AB24 3UE, Scotland. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Kaye, Jeffrey] Oregon Hlth & Sci Univ, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97239 USA. [Kaye, Jeffrey] Portland VA Med Ctr, Portland, OR USA. RP Roark, B (reprint author), Oregon Hlth & Sci Univ, Dept Biomed Engn, Ctr Spoken Language Understanding, Portland, OR 97239 USA. EM roark@cslu.ogi.edu; m.mitchell@abdn.ac.uk; hosom@cslu.ogi.edu; hollingk@gmail.com; kaye@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU National Science Foundation (NSF) [IIS-0447214, BCS-0826654]; National Institute of Health/National Institute of Aging (NIH/NIA) [P30AG08017, R01AG024059]; Oregon Center for Aging and Technology (ORCATECH, NIH) [1P30AG024978-01]; Oregon Partnership for Alzheimer's Research FX Manuscript received August 06, 2010; revised November 05, 2010; accepted January 17, 2011. Date of publication February 07, 2011; date of current version July 20, 2011. This research was supported in part by the National Science Foundation (NSF) under Grants #IIS-0447214 and #BCS-0826654, National Institute of Health/National Institute of Aging (NIH/NIA) grants #P30AG08017 and #R01AG024059, and pilot grants from the Oregon Center for Aging and Technology (ORCATECH, NIH #1P30AG024978-01) and the Oregon Partnership for Alzheimer's Research. Any opinions, findings, conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the NSF or NIH. The associate editor coordinating the review of this manuscript and approving it for publication was Dr. Gokhan Tur. NR 44 TC 34 Z9 35 U1 1 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1558-7916 J9 IEEE T AUDIO SPEECH JI IEEE Trans. Audio Speech Lang. Process. PD SEP PY 2011 VL 19 IS 7 BP 2081 EP 2090 DI 10.1109/TASL.2011.2112351 PG 10 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 805NL UT WOS:000293734500020 PM 22199464 ER PT J AU Weinstein, MM Pretorius, DH Jung, SA Wan, JJ Nager, CW Mittal, RK AF Weinstein, Milena M. Pretorius, Dolores H. Jung, Sung-Ae Wan, Jennifer J. Nager, Charles W. Mittal, Ravinder K. TI Anal sphincter complex muscles defects and dysfunction in asymptomatic parous women SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Anal manometry; Anal sphincter complex; Three-dimensional ultrasound; Vaginal manometry ID TRANSPERINEAL 3-DIMENSIONAL ULTRASOUND; PELVIC FLOOR MUSCLES; FECAL INCONTINENCE; VAGINAL DELIVERY; URINARY-INCONTINENCE; PRIMIPAROUS WOMEN; PRESSURE; SYMPTOMS AB Introduction and hypothesis We aimed to determine anatomy and function of anal sphincter complex using three-dimensional ultrasound (3D-US) and manometry in asymptomatic parous women. Methods 3D-US of puborectalis muscle (PRM), external (EAS), and internal anal sphincters (IAS) anatomy was performed in 45 women without pelvic floor dysfunction. To assess function, rest and squeeze vaginal and anal pressures were measured. Based on 3D-US, subjects were divided into injured and uninjured groups. Results Forty-four of 45 subjects had adequate PRM images. The injured PRM (N = 14) group had significantly lower vaginal pressures as compared with uninjured PRM group (N = 30; p = 0.001). Four of 45 subjects with IAS and EAS defects had lower resting and squeeze anal canal pressure. Muscle injury to IAS, EAS and PRM in the same individual was uncommon. Conclusions In asymptomatic parous women, PRM defects were more common than the EAS/IAS defects but defects in more than one muscle were infrequent. Subjects with injured PRM had low vaginal pressure than the ones without. C1 [Jung, Sung-Ae; Mittal, Ravinder K.] Univ Calif San Diego, Div Gastroenterol, Dept Internal Med, San Diego, CA 92161 USA. [Weinstein, Milena M.; Pretorius, Dolores H.; Jung, Sung-Ae; Wan, Jennifer J.; Nager, Charles W.; Mittal, Ravinder K.] Univ Calif San Diego, Pelv Floor Funct & Disorder Grp, San Diego, CA 92161 USA. [Weinstein, Milena M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Vincent Gynecol,Div Urogynecol & Reconstruct, Boston, MA USA. [Pretorius, Dolores H.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92161 USA. [Jung, Sung-Ae] Ewha Womans Univ, Coll Med, Seoul, South Korea. [Nager, Charles W.] Univ Calif San Diego, Dept Reprod Med, Div Urogynecol & Reconstruct Pelv Surg, San Diego, CA 92161 USA. RP Mittal, RK (reprint author), Univ Calif San Diego, Div Gastroenterol, Dept Internal Med, GI 111D,3350 La Jolla Village Dr, San Diego, CA 92161 USA. EM rmittal@ucsd.edu FU NIH [DK60733] FX Financially supported by NIH RO1 grant DK60733 NR 27 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD SEP PY 2011 VL 22 IS 9 BP 1143 EP 1150 DI 10.1007/s00192-011-1446-8 PG 8 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 813FH UT WOS:000294351700009 PM 21604060 ER PT J AU Aghi, MK Walcott, BP Nahed, BV Cvetanovich, GL Kahle, KT Redjal, N Coumans, JV AF Aghi, Manish K. Walcott, Brian P. Nahed, Brian V. Cvetanovich, Gregory L. Kahle, Kristopher T. Redjal, Navid Coumans, Jean-Valery TI Determinants of initial bone graft volume loss in posterolateral lumbar fusion SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Bone graft; Lumbar spine; Pseudarthrosis; Smoking; Spinal fusion ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SPINAL-FUSION; MODEL; NICOTINE; SMOKING; RAT AB Bone graft volume decreases postoperatively without known etiology. We sought to determine the bone graft volume over time in 15 consecutive patients undergoing a single-level, instrumented, posterolateral lumbar fusion for degeneration causing mechanical pain or spondylolisthesis, and to identify factors associated with bone graft resorption. Following Institutional Review Board approval, a retrospective analysis was performed. Immediate and 3-month postoperative lumbar spine CT scans were imported into imaging software for volumetric analysis. We found that the 15 patients averaged approximately 11% graft volume loss at 3 months postoperatively. All patients exhibited volumetric graft loss on each side (range, 0.3-45%). A paired t-test revealed that immediate postoperative graft volume on a patient's left or right did not reflect graft volume on that side 3 months postoperatively (p = 0.0008). Gender, age, history of prior operation, history of regular exercise, body mass index, level fused, operative time, initial graft volume, and laterality did not influence percentage volumetric loss (p = 0.1-0.5). Interestingly, people who smoked cigarettes (range, 10-40 pack-years) exhibited 27% graft loss, compared to 7% in those who did not (Spearman p = 0.009 graft loss versus pack-years smoked). We concluded that bone graft exhibited resorption 3 months postoperatively on both sides of all patients in this series, and that smoking was significantly associated with increased bone graft resorption. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.; Redjal, Navid; Coumans, Jean-Valery] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Walcott, Brian P.; Nahed, Brian V.; Cvetanovich, Gregory L.; Kahle, Kristopher T.; Redjal, Navid; Coumans, Jean-Valery] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Aghi, Manish K.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, White Bldg,Room 502,55 Fruit St, Boston, MA 02114 USA. EM Walcott.brian@mgh.harvard.edu NR 27 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2011 VL 18 IS 9 BP 1193 EP 1196 DI 10.1016/j.jocn.2011.02.017 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 812VC UT WOS:000294320000010 PM 21745744 ER PT J AU Kahle, KT Walcott, BP Nahed, BV Barnard, ZR Lo, EH Buonanno, FS Venna, N Ning, MM AF Kahle, Kristopher T. Walcott, Brian P. Nahed, Brian V. Barnard, Zachary R. Lo, Eng H. Buonanno, Ferdinando S. Venna, Nagagopal Ning, MingMing TI Cerebral edema and a transtentorial brain herniation syndrome associated with pandemic swine influenza A (H1N1) virus infection SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Brain edema; H1N1 subtype; Inappropriate ADH syndrome; Influenza A virus; Intracranial pressure; Respiratory distress syndrome; Systemic inflammatory response syndrome ID NEUROLOGIC COMPLICATIONS; ENCEPHALITIS; CHILDREN; MEXICO AB Acute encephalitis, encephalopathy, and seizures are known rare neurologic sequelae of respiratory tract infection with seasonal influenza A and B virus, but the neurological complications of the pandemic 2009 swine influenza A (H1N1) virus, particularly in adults, are ill-defined. We document two young adults suffering from H1N1-associated acute respiratory distress syndrome and renal failure who developed cerebral edema. The patients acutely developed a transtentorial brain herniation syndrome including a unilateral third nerve palsy (dilated and unresponsive pupils), elevated intracranial pressure, coma, and radiological evidence of diffuse cerebral edema. In both patients, neurological deterioration occurred in the context of hyponatremia and a systemic inflammatory state. These patients illustrate that severe neurologic complications, including malignant cerebral edema, can occur in adults infected with H1N1 virus, and illustrate the need for close neurological monitoring of potential neurological morbidities in future pandemics. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Kahle, Kristopher T.; Walcott, Brian P.; Nahed, Brian V.; Barnard, Zachary R.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kahle, Kristopher T.; Walcott, Brian P.; Nahed, Brian V.; Barnard, Zachary R.; Lo, Eng H.; Buonanno, Ferdinando S.; Venna, Nagagopal; Ning, MingMing] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lo, Eng H.; Buonanno, Ferdinando S.; Venna, Nagagopal; Ning, MingMing] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, White Bldg,Room 502,55 Fruit St, Boston, MA 02114 USA. EM Walcott.brian@mgh.harvard.edu FU NINDS NIH HHS [R01 NS067139, RC2 NS069335, P01 NS055104] NR 14 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD SEP PY 2011 VL 18 IS 9 BP 1245 EP 1248 DI 10.1016/j.jocn.2011.01.014 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 812VC UT WOS:000294320000023 PM 21742505 ER PT J AU Steensma, DP AF Steensma, David P. TI Art of Oncology: New Voices Wanted SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Steensma, David/0000-0001-5130-9284 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2011 VL 29 IS 25 BP 3343 EP 3344 DI 10.1200/JCO.2011.37.7242 PG 2 WC Oncology SC Oncology GA 814EO UT WOS:000294429900007 PM 21788569 ER PT J AU Wright, JD Neugut, AI Wilde, ET Buono, DL Malin, J Tsai, WY Hershman, DL AF Wright, Jason D. Neugut, Alfred I. Wilde, Elizabeth T. Buono, Donna L. Malin, Jennifer Tsai, Wei Y. Hershman, Dawn L. TI Physician Characteristics and Variability of Erythropoiesis-Stimulating Agent Use Among Medicare Patients With Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; PATIENTS RECEIVING CHEMOTHERAPY; OFF-LABEL USE; UNITED-STATES; AMERICAN SOCIETY; EORTC GUIDELINES; ANEMIC PATIENTS; BREAST-CANCER; PATTERNS; ONCOLOGY AB Purpose Drugs are usually approved for a specific indication on the basis of randomized trials. However, once approved, these treatments are often used differently than as tested in trials. We performed an analysis to determine the patterns of use of erythropoiesis-stimulating agents (ESAs). Methods We used the Surveillance, Epidemiology, and End Results-Medicare database to identify patients age 65 years or older with breast, lung, or colon cancer diagnosed between 1995 and 2005 who had one ESA and chemotherapy claim. Associations of patient, tumor, and physician-related factors with receipt of ESAs were analyzed. Results Of 21,091 patients analyzed, 5,099 (24.2%) received ESAs for 1 week or less (misuse), and 1,601 (7.6%) received ESAs for more than 14 weeks (prolonged use). Receipt of ESAs while not actively receiving chemotherapy (off label) occurred in 2,876 patients (13.6%). In a multivariable analysis, ESA misuse was associated with MD degree, female sex of physician, and earlier year of medical school graduation. Private practice physicians (odds ratio [OR], 0.78; 95% CI, 0.72 to 0.84) and high-volume physicians (OR, 0.78; 95% CI, 0.72 to 0.85) were less likely to use 1 week or less of ESA treatment. Treatment by high-volume oncologists (OR, 1.33; 95% CI, 1.14 to 1.55) and by oncologists who graduated from US medical schools (OR, 1.26; 95% CI, 1.12 to 1.42) predicted prolonged-duration ESA use, whereas female oncologists (OR, 0.79; 95% CI, 0.68 to 0.93) were less likely to prescribe prolonged ESA treatment. Private practice physicians (OR, 1.18; 95% CI, 1.02 to 1.38) and high-volume providers (OR, 1.58; 95% CI, 1.33 to 1.87) were more likely to prescribe more than 24 weeks of ESA treatment. Conclusion Our study demonstrated widespread variability in the use of ESAs. Physician characteristics exerted substantial influence on ESA use. Policies to discourage inappropriate use of cancer therapies are needed. J Clin Oncol 29:3408-3418. (C) 2011 by American Society of Clinical Oncology C1 [Malin, Jennifer; Hershman, Dawn L.] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Malin, Jennifer] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Hershman, DL (reprint author), Columbia Univ, Med Ctr, 161 Ft Washington Ave,10-1068, New York, NY 10032 USA. EM dlh23@columbia.edu FU National Cancer Institute [R01CA134964] FX Supported in part by Grant No. R01CA134964 from the National Cancer Institute (D.L.H.). NR 38 TC 17 Z9 17 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2011 VL 29 IS 25 BP 3408 EP 3418 DI 10.1200/JCO.2010.34.5462 PG 11 WC Oncology SC Oncology GA 814EO UT WOS:000294429900019 PM 21810679 ER PT J AU Richards, CJ Je, YJ Schutz, FAB Heng, DYC Dallabrida, SM Moslehi, JJ Choueiri, TK AF Richards, Christopher J. Je, Youjin Schutz, Fabio A. B. Heng, Daniel Y. C. Dallabrida, Susan M. Moslehi, Javid J. Choueiri, Toni K. TI Incidence and Risk of Congestive Heart Failure in Patients With Renal and Nonrenal Cell Carcinoma Treated With Sunitinib SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANGIOGENESIS INHIBITOR BEVACIZUMAB; FOOT SKIN REACTION; CANCER-PATIENTS; PHASE-II; GROWTH-FACTOR; VENOUS THROMBOEMBOLISM; NEUROENDOCRINE TUMORS; JAPANESE PATIENTS; CLINICAL-TRIALS; METAANALYSIS AB Purpose Sunitinib is a multitargeted receptor tyrosine kinase inhibitor approved for treatment of renal cell carcinoma (RCC) and GI stromal tumor. Congestive heart failure (CHF) is an important adverse effect that has been reported with sunitinib, but overall incidence and relative risk (RR) remain undefined. We performed an up-to-date meta-analysis to determine the risk of developing CHF in patients with both RCC and non-RCC tumors treated with sunitinib. Methods Medline databases were searched for articles published between January 1966 and February 2011. Eligible studies were limited to phase II and III trials of sunitinib with adequate safety reporting in patients with cancer of any tumor type. Summary incidence, RR, and 95% CIs were calculated using random-or fixed-effects models based on the heterogeneity of included studies. Results A total of 6,935 patients were included. Overall incidence for all-and high-grade CHF in sunitinib-treated patients was 4.1% (95% CI, 1.5% to 10.6%) and 1.5% (95% CI, 0.8% to 3.0%), respectively. RR of all-and high-grade CHF in sunitinib-treated patients compared with placebo-treated patients was 1.81 (95% CI, 1.30 to 2.50; P < .001) and 3.30 (95% CI, 1.29 to 8.45; P = .01), respectively. On subgroup analysis, there was no difference observed in CHF incidence for patients with RCC versus non-RCC or in trials with or without cardiac monitoring. No evidence of publication bias was observed. Conclusion Sunitinib use is associated with increased risk of CHF in patients with cancer. J Clin Oncol 29:3450-3456. (C) 2011 by American Society of Clinical Oncology C1 [Richards, Christopher J.; Schutz, Fabio A. B.; Moslehi, Javid J.; Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Richards, Christopher J.; Schutz, Fabio A. B.; Dallabrida, Susan M.; Moslehi, Javid J.; Choueiri, Toni K.] Harvard Univ, Sch Med, Boston, MA USA. [Je, Youjin] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Dallabrida, Susan M.] Childrens Hosp, Boston, MA 02115 USA. [Dallabrida, Susan M.] Biogen Idec Inc, Boston, MA USA. [Schutz, Fabio A. B.] Hosp Sao Jose, Sao Paulo, Brazil. [Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. RP Choueiri, TK (reprint author), 450 Brookline Ave,DANA 1230, Boston, MA 02215 USA. EM toni_choueiri@dfci.harvard.edu FU Trust Family Research Fund for Kidney Cancer FX Supported by the Trust Family Research Fund for Kidney Cancer. NR 51 TC 74 Z9 74 U1 2 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2011 VL 29 IS 25 BP 3450 EP 3456 DI 10.1200/JCO.2010.34.4309 PG 7 WC Oncology SC Oncology GA 814EO UT WOS:000294429900024 PM 21810682 ER PT J AU Haq, R Fisher, DE AF Haq, Rizwan Fisher, David E. TI Biology and Clinical Relevance of the Micropthalmia Family of Transcription Factors in Human Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RENAL-CELL CARCINOMAS; MELANOCYTE-STIMULATING HORMONE; CUTANEOUS MALIGNANT-MELANOMA; HEPATOCYTE GROWTH-FACTOR; WAARDENBURG-SYNDROME; SOFT PARTS; MICROPHTHALMIA GENE; UP-REGULATION; FACTOR MITF; TFE3 GENE AB Members of the micropthalmia (MiT) family of transcription factors (MITF, TFE3, TFEB, and TFEC) are physiologic regulators of cell growth, differentiation, and survival in several tissue types. Because their dysregulation can lead to melanoma, renal cell carcinoma, and some sarcomas, understanding why these genes are co-opted in carcinogenesis may be of general utility. Here we describe the structure of the MiT family of proteins, the ways in which they are aberrantly activated, and the molecular mechanisms by which they promote oncogenesis. We discuss how meaningful understanding of these mechanisms can be used to elucidate the oncogenic process. Because the expression of these proteins is essential for initiating and maintaining the oncogenic state in some cancer types, we propose ways that they can be exploited to prevent, diagnose, and rationally treat these malignancies. C1 [Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Dermatol & Cutaneous Biol Res Ctr, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Dermatol & Cutaneous Biol Res Ctr, 55 Fruit St, Boston, MA 02114 USA. EM dfisher3@partners.org RI di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 NR 102 TC 55 Z9 57 U1 0 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2011 VL 29 IS 25 BP 3474 EP 3482 DI 10.1200/JCO.2010.32.6223 PG 9 WC Oncology SC Oncology GA 814EO UT WOS:000294429900027 PM 21670463 ER PT J AU Celano, CM Torri, A Seiner, S AF Celano, Christopher M. Torri, Andrea Seiner, Stephen TI Takotsubo Cardiomyopathy After Electroconvulsive Therapy A Case Report and Review SO JOURNAL OF ECT LA English DT Review DE takotsubo cardiomyopathy; electroconvulsive therapy; major depressive disorder ID TAKO-TSUBO CARDIOMYOPATHY; DYSFUNCTION; STRESS; SINGLE AB Takotsubo cardiomyopathy (TCM) is a syndrome of reversible stress-induced cardiomyopathy associated with profound emotional stress and a variety of medical illnesses and procedures, including electroconvulsive therapy (ECT). We describe 1 case of ECT-induced TCM followed by a successful retrial of ECT. We further discuss the management of ECT-induced TCM and the decision to perform a second trial of ECT in patients with this complication. Given the current understanding of the pathogenesis of TCM, it is appropriate to discontinue ECT during the acute setting of TCM. After the resolution of the acute episode of TCM, a second trial of ECT may be warranted depending on the severity of psychiatric illness (ie, suicidal ideation, catatonia, psychotic symptoms). If a retrial of ECT is performed, oral and intravenous beta-blockers should be used for cardioprotection, and patients should be monitored for signs and symptoms of an evolving cardiomyopathy. It is preferable to perform retrials of ECT-at least initially-in a general hospital setting, where immediate invasive monitoring and intensive treatments are available in the event of acute cardiac failure. C1 [Celano, Christopher M.; Seiner, Stephen] McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. [Celano, Christopher M.; Torri, Andrea; Seiner, Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Torri, Andrea] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Celano, CM (reprint author), McLean Hosp, Dept Psychiat, Mail Stop 109,115 Mill St, Belmont, MA 02478 USA. EM ccelano@partners.org NR 17 TC 8 Z9 8 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD SEP PY 2011 VL 27 IS 3 BP 221 EP 223 DI 10.1097/YCT.0b013e31821537c0 PG 3 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 811XC UT WOS:000294250500012 PM 21673587 ER PT J AU Dowds, MM Lee, PH Sheer, JB O'Neil-Pirozzi, TM Xenopoulos-Oddsson, A Goldstein, R Zainea, KL Glenn, MB AF Dowds, Murdo M. Lee, Patricia H. Sheer, Jeffrey B. O'Neil-Pirozzi, Therese M. Xenopoulos-Oddsson, Annette Goldstein, Richard Zainea, Kathryn L. Glenn, Mel B. TI Electronic Reminding Technology Following Traumatic Brain Injury: Effects on Timely Task Completion SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE cognitive disability; cognitive impairment; functional independence; handheld computers; memory disorders; prospective memory; rehabilitation; traumatic brain injury ID MEMORY AID; HEAD-INJURY; REHABILITATION; DEVICES; DISABILITIES; ADULTS; TRIAL; PDAS AB Objective: To determine whether automated reminders from 2 contemporary personal digital assistant (PDA) devices produce higher rates of timely task completion in people with traumatic brain injury (TBI). Setting: Outpatient and community rehabilitation settings. Participants: Thirty-six adults aged 18 to 66 years with TBI and self-determined complaints of memory impairment. Measures: Timely completion rates for assigned memory tasks under 4 randomly assigned memory aid conditions. Results: Significantly, higher completion rates were found when using either PDA device when compared with a combined baseline and paper memory aid condition (for Palm OS device, Incidence Rate Ratio [IRR] = 2.14, P < .0005, CI [confidence interval] = 1.77-2.59; for Microsoft Pocket PCOS device, IRR = 1.47, P < .001, CI = 1.18-1.82). A significant difference in completion rates was also found between the 2 PDA devices (IRR = 1.46, P < .0005, CI = 1.26-1.70), with the Palm version producing the better scores. Conclusions: Substantially higher rates of task completion (more than double in some cases) when using either PDA device suggest that rehabilitation clinicians can make productive use of PDA-based memory aids in their TBI patient populations. The strength of the effects of PDA device usage argues for further investigation of the impact of device usage on quality-of-life and costs of care, and of personal and caregiver factors predictive of successful and sustained device usage. C1 [Lee, Patricia H.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Sheer, Jeffrey B.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [O'Neil-Pirozzi, Therese M.] Northeastern Univ, Speech Language Pathol & Audiol Dept, Boston, MA 02115 USA. [Xenopoulos-Oddsson, Annette; Goldstein, Richard; Glenn, Mel B.] Harvard Univ, Sch Med, Dept PM&R, Spaulding Rehabil Hosp, Boston, MA 02115 USA. [Zainea, Kathryn L.] Spaulding Rehabil Hosp, Assist Technol Ctr, Boston, MA USA. RP Dowds, MM (reprint author), 5 Whittier Pl,Suite 101, Boston, MA 02114 USA. EM murdomdowdsphd@verizon.net FU National Institute on Disability and Rehabilitation Research, US Department of Education [H113A0101607A] FX This study was funded by grant# H113A0101607A from the National Institute on Disability and Rehabilitation Research, US Department of Education. The authors wish to thank Roberta DePompei, PhD, for her leadership of the Assistive Technology Collaborative, and for her support for this component of the project. NR 44 TC 11 Z9 11 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-9701 J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD SEP-OCT PY 2011 VL 26 IS 5 BP 339 EP 347 DI 10.1097/HTR.0b013e3181f2bf1d PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 814VO UT WOS:000294485500002 PM 21464734 ER PT J AU Bogoch, II Davis, BT Venna, N AF Bogoch, Isaac I. Davis, Benjamin T. Venna, Nagagopal TI Reversible dementia in a patient with central nervous system escape of human immunodeficiency virus SO JOURNAL OF INFECTION LA English DT Article DE HIV; AIDS; Dementia ID ANTIRETROVIRAL THERAPY; NEUROCOGNITIVE DISORDERS; PERFORMANCE; FLUID AB HIV-associated neurocognitive disorders (HAND) are a group of conditions ranging from asymptomatic neurocognitive impairment to disabling dementia. The clinical spectrum and pathogenesis of these disorders is changing in the era of highly active antiretroviral therapy (HAART). High levels of HIV may exist in the cerebrospinal fluid (CSF) of some patients despite suppression of serum viral loads by HAART. We report a case of a 51-year-old male with profound levels of HIV in the CSF despite low serum levels. Adjusting his HAART regimen based on HIV genotype susceptibility data and a CNS Penetrating Effectiveness (CPE) score resulted in a dramatic improvement in cognitive function. Progressive dementia in this context is a rare but emerging trend and may be reversible. (C) 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved. C1 [Bogoch, Isaac I.; Davis, Benjamin T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Venna, Nagagopal] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. [Bogoch, Isaac I.; Davis, Benjamin T.; Venna, Nagagopal] Harvard Univ, Sch Med, Boston, MA USA. RP Bogoch, II (reprint author), Massachusetts Gen Hosp, Div Infect Dis, COX 5,55 Fruit St, Boston, MA 02114 USA. EM ibogoch@partners.org NR 9 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD SEP PY 2011 VL 63 IS 3 BP 236 EP 239 DI 10.1016/j.jinf.2011.05.011 PG 4 WC Infectious Diseases SC Infectious Diseases GA 814JX UT WOS:000294448000008 PM 21658774 ER PT J AU Anghel, S Correa-Rocha, R Budinska, E Boligan, KF Fontao, L Ghanem, GE Fisher, DE Levy, F Delorenzi, M Piguet, V AF Anghel, Silvia Correa-Rocha, Rafael Budinska, Eva Boligan, Kayluz Frias Fontao, Lionel Ghanem, Ghanem E. Fisher, David E. Levy, Frederic Delorenzi, Mauro Piguet, Vincent TI Global Analysis of Transcription Reveals BCSC-1 as a Melanoma Tumor Suppressor that Downregulates MITF SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 07-10, 2011 CL Barcelona, SPAIN SP European Soc Dermatol Res C1 [Anghel, Silvia; Correa-Rocha, Rafael; Boligan, Kayluz Frias; Fontao, Lionel; Piguet, Vincent] Univ Hosp & Med Sch Geneva, Dept Dermatol & Venerol, Geneva, Switzerland. [Anghel, Silvia; Correa-Rocha, Rafael; Boligan, Kayluz Frias; Fontao, Lionel; Piguet, Vincent] Univ Hosp & Med Sch Geneva, Dept Microbiol, Geneva, Switzerland. [Anghel, Silvia; Correa-Rocha, Rafael; Boligan, Kayluz Frias; Fontao, Lionel; Piguet, Vincent] Univ Hosp & Med Sch Geneva, Dept Mol Med, Geneva, Switzerland. [Correa-Rocha, Rafael] Hosp Gen Univ Gregorio Maranon, Lab Molec Immunobiol, Madrid, Spain. [Budinska, Eva; Delorenzi, Mauro] Univ Lausanne, Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland. [Budinska, Eva] Masaryk Univ, Inst Biostat & Anal, Brno, Czech Republic. [Boligan, Kayluz Frias] Nat Inst Oncol & Radiobiol, Dept Basic Res, Havana, Cuba. [Levy, Frederic] Univ Lausanne, Ludwig Inst Canc Res, CH-1066 Epalinges, Switzerland. [Ghanem, Ghanem E.] Univ Libre Bruxelles, Inst Jules Bordet, Lab Oncol & Chirurg Expt, Brussels, Belgium. [Fisher, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Levy, Frederic] Debiopharm SA, Lausanne, Switzerland. [Delorenzi, Mauro] ISREC SV EPFL, Nat Ctr Competence Res Mol Oncol, Lausanne, Switzerland. [Piguet, Vincent] Cardiff Univ, Welsh Inst Dermatol, Dept Dermatol & Wound Healing, Cardiff, S Glam, Wales. [Piguet, Vincent] Univ Wales Hosp, Cardiff CF4 4XW, S Glam, Wales. RI Correa-Rocha, Rafael/C-8213-2011; Budinska, Eva/F-2698-2011 OI Correa-Rocha, Rafael/0000-0003-3456-9986; Budinska, Eva/0000-0002-9004-9187 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2011 VL 131 SU 2 BP S66 EP S66 PG 1 WC Dermatology SC Dermatology GA 813IY UT WOS:000294361300394 ER PT J AU Jalili, A Wagner, C Mertz, KD Pashenkov, M Ramaswamy, S Stingl, G Wagner, SN AF Jalili, Ahmad Wagner, Christine Mertz, Kirsten D. Pashenkov, Mikhail Ramaswamy, Sridhar Stingl, Georg Wagner, Stephan N. TI Cyclin dependent kinases 2 and 4 are downstream targets of the mitogen activated protein kinase pathway in human melanoma and are of potential therapeutic application SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the European-Society-for-Dermatological-Research CY SEP 07-10, 2011 CL Barcelona, SPAIN SP European Soc Dermatol Res C1 [Jalili, Ahmad; Wagner, Christine; Mertz, Kirsten D.; Pashenkov, Mikhail; Stingl, Georg; Wagner, Stephan N.] Med Univ Vienna, Dept Dermatol, DIAID, Vienna, Austria. [Ramaswamy, Sridhar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2011 VL 131 SU 2 BP S107 EP S107 PG 1 WC Dermatology SC Dermatology GA 813IY UT WOS:000294361300636 ER PT J AU Madison, KM Volpp, KG Halpern, SD AF Madison, Kristin M. Volpp, Kevin G. Halpern, Scott D. TI The Law, Policy, and Ethics of Employers' Use of Financial Incentives to Improve Health SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID WEIGHT-LOSS; REDUCTION; BEHAVIORS; UNDUE; SICK; RISK C1 [Madison, Kristin M.; Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn Wharton Sch, Dept Hlth Care Management, Philadelphia, PA USA. [Volpp, Kevin G.] Univ Penn Wharton Sch, Sch Med, Philadelphia, PA USA. [Volpp, Kevin G.; Halpern, Scott D.] Univ Penn, Leonard Davis Inst Ctr Hlth Incent, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Penn CMU Roybal Ctr Behav Econ & Hlth P30, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Halpern, Scott D.] Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. RP Madison, KM (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. NR 66 TC 23 Z9 23 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD FAL PY 2011 VL 39 IS 3 BP 450 EP 468 DI 10.1111/j.1748-720X.2011.00614.x PG 19 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 810MI UT WOS:000294129000014 PM 21871042 ER PT J AU Palmer, CD Mancuso, CJ Weiss, JP Serhan, CN Guinan, EC Levy, O AF Palmer, Christine D. Mancuso, Christy J. Weiss, Jerrold P. Serhan, Charles N. Guinan, Eva C. Levy, Ofer TI 17(R)-Resolvin D1 differentially regulates TLR4-mediated responses of primary human macrophages to purified LPS and live E. coli SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE eicosanoid; TNF; IL-6; resolution of inflammation ID LIPOPOLYSACCHARIDE-BINDING PROTEIN; INFLAMMATORY-BOWEL-DISEASE; MEDIATOR RESOLVIN E1; TOLL-LIKE RECEPTORS; ACUTE LUNG INJURY; NF-KAPPA-B; ESCHERICHIA-COLI; GENE-EXPRESSION; LIPOXIN A(4); ALTERNATIVE ACTIVATION AB Detection and clearance of bacterial infection require balanced effector and resolution signals to avoid chronic inflammation. Detection of GNB LPS by TLR4 on m(phi) induces inflammatory responses, contributing to chronic inflammation and tissue injury. LXs and Rvs are endogenous lipid mediators that enhance resolution of inflammation, and their actions on primary human m(phi) responses toward GNB are largely uncharacterized. Here, we report that LXA(4), LXB(4), and RvD1, tested at 0.1-1 mu M, inhibited LPS-induced TNF production from primary human m(phi), with ATL and 17(R)-RvD1, demonstrating potent inhibition at 0.1 mu M. In addition, 17(R)RvD1 inhibited LPS-induced primary human m(phi) production of IL-7, IL-12p70, GM-CSF, IL-8, CCL2, and MIP-1 alpha without reducing that of IL-6 or IL-10. Remarkably, when stimulated with live Escherichia coli, m(phi) treated with 17(R)-RvD1 demonstrated increased TNF production and enhanced internalization and killing of the bacteria. 17(R)-RvD1-enhanced TNF, internalization, and killing were not evident for an lpxM mutant of E. coli expressing hypoacylated LPS with reduced inflammatory activity. Furthermore, 17(R)-RvD1-enhanced, E. coli-induced TNF production was evident in WT but not TLR4-deficient murine m(phi). Thus, Rvs differentially modulate primary human m(phi) responses to E. coli in an LPS- and TLR4-dependent manner, such that this Rv could promote resolution of GNB/LPS-driven inflammation by reducing m(phi) proinflammatory responses to isolated LPS and increasing m(phi) responses important for clearance of infection. J. Leukoc. Biol. 90: 459-470; 2011. C1 [Palmer, Christine D.; Mancuso, Christy J.; Levy, Ofer] Childrens Hosp, Div Infect Dis, Dept Med, Boston, MA 02115 USA. [Palmer, Christine D.; Serhan, Charles N.; Guinan, Eva C.; Levy, Ofer] Harvard Univ, Sch Med, Boston, MA USA. [Weiss, Jerrold P.] Univ Iowa, Inflammat Program, Coralville, IA USA. [Weiss, Jerrold P.] Univ Iowa, Dept Med, Coralville, IA USA. [Serhan, Charles N.] Brigham & Womens Hosp, Harvard Inst Med, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Ctr Translat Res, Boston, MA 02115 USA. RP Levy, O (reprint author), Childrens Hosp, Div Infect Dis, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM ofer.levy@childrens.harvard.edu FU Dana Human Immunology Award; Defense Advanced Projects Agency (DARPA); Greene Fund; NIH [R21 HL089659-01A1, RO1 AI067353]; Thrasher Foundation; American Recovery and Reinvestmant Act NIH Administrative Supplement [3R01AI067353-05S1]; NIH (Bethesda, MD, USA) [R01GM038765, P01GM095467]; Dartmouth Center for Medical FX Funding for this project was provided by a Dana Human Immunology Award (to O.L. and E. C. G.), the Defense Advanced Projects Agency (DARPA; to E. C. G. and O.L.), the Greene Fund (to E. C. G.), and NIH R21 HL089659-01A1 (to E. C. G. and O.L.). C.J.M. acknowledges the support of the Thrasher Foundation. The laboratory of O.L. is supported by NIH RO1 AI067353 and an American Recovery and Reinvestmant Act NIH Administrative Supplement 3R01AI067353-05S1. Work in the C.N.S. laboratory was supported in part by NIH (Bethesda, MD, USA), grant nos. R01GM038765 and P01GM095467 (to C.N.S.). C. P. and O.L. acknowledge support from the Dartmouth Center for Medical Countermeasures Pilot Project. We thank all adult volunteers who donated blood and Drs. K. Kronforst and K. Nathe for phlebotomy. We thank biostatistician Dr. Leslie Kalish (CHB Clinical Research Program) for critical review of statistical analyses. We thank Dr. Christian Raetz (Duke University Medical School, Durham, NC, USA) for providing the WT and isogenic lpxM mutant strains of E. coli and Dr. Douglas Golenbock (University of Massachusetts Medical School, Worcester, MA, USA) for providing us with WT and TLR4-deficient murine mphi. NR 76 TC 22 Z9 22 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 2011 VL 90 IS 3 BP 459 EP 470 DI 10.1189/jlb.0311145 PG 12 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 814IK UT WOS:000294441700007 PM 21653234 ER PT J AU Wu, YT Reese, TG Cao, HH Hrovat, MI Toddes, SP Lemdiasov, RA Ackerman, JL AF Wu, Yaotang Reese, Timothy G. Cao, Haihui Hrovat, Mirko I. Toddes, Steven P. Lemdiasov, Rostislav A. Ackerman, Jerome L. TI Bone Mineral Imaged In Vivo by P-31 Solid State MRI of Human Wrists SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE bone; solid state MRI; P-31 SMRI; UTE; osteoporosis; WASPI ID PROTON PROJECTION MRI; OSTEOPOROSIS; MANAGEMENT; PHOSPHORUS; DENSITY; MATRIX; WASPI AB Purpose: To implement solid state P-31 MRI (P-31 SMRI) in a clinical scanner to visualize bone mineral. Materials and Methods: Wrists of seven healthy volunteers were scanned. A quadrature wrist P-31 transmit/receive coil provided strong B-1 and good signal-to-noise ratio (SNR). A H-1-P-31 frequency converter was constructed to enable detection of the P-31 signal by means of the H-1 channel. Data points lost in the receiver dead time were recovered by a second acquisition with longer dwell time and lower gradient strength. Results: Three-dimensional P-31 images, showing only bone mineral of the wrist, were obtained with a clinical 3 Tesla (T) scanner. In the best overall case an image with isotropic resolution of similar to 5.1 mm and SNR of 30 was obtained in 37 min. P-31 NMR properties (resonance line width 2 kHz and T-1 17-19 s) of in vivo human bone mineral were measured. Conclusion: In vivo P-31 SMRI visualization of human wrist bone mineral with a clinical MR scanner is feasible with suitable modifications to circumvent the scanners' limitations in reception of short-T-2 signals. Frequency conversion methodology is useful for implementing P-31 SMRI measurements on scanners which do not have multinuclear capability or for which the multinuclear receiver dead time is excessive. C1 [Wu, Yaotang; Cao, Haihui; Ackerman, Jerome L.] Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Wu, Yaotang; Reese, Timothy G.; Cao, Haihui; Ackerman, Jerome L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wu, Yaotang; Reese, Timothy G.; Cao, Haihui; Ackerman, Jerome L.] Harvard Univ, Sch Med, Boston, MA USA. [Hrovat, Mirko I.] Mirtech Inc, Brockton, MA USA. [Toddes, Steven P.; Lemdiasov, Rostislav A.] InsightMRI, Leominster, MA USA. RP Wu, YT (reprint author), Childrens Hosp, Dept Orthoped Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM yaotang.wu@childrens.harvard.edu RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU National Institute of Biomedical Imaging and Bioengineering [R01-EB004012]; National Center for Research Resources [P41-RR14075]; Peabody Foundation; Athinoula A. Mar Linos Center for Biomedical Imaging; Orthopedic Surgery Foundation of the Children's Hospital, Boston; MIND Institute FX Contract grant sponsor: National Institute of Biomedical Imaging and Bioengineering; Contract grant number: R01-EB004012; Contract grant sponsor: National Center for Research Resources; Contract grant number: P41-RR14075; Contract grant sponsors: the Peabody Foundation; the Athinoula A. Mar Linos Center for Biomedical Imaging; the Orthopedic Surgery Foundation of the Children's Hospital, Boston; the MIND Institute. NR 19 TC 9 Z9 9 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD SEP PY 2011 VL 34 IS 3 BP 623 EP 633 DI 10.1002/jmri.22637 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 814IW UT WOS:000294442900018 PM 21761459 ER PT J AU Ren, YM Lee, MY Schliffke, S Paavola, J Amos, PJ Ge, X Ye, MY Zhu, SJ Senyei, G Lum, L Ehrlich, BE Qyang, YB AF Ren, Yongming Lee, Min Young Schliffke, Simon Paavola, Jere Amos, Peter J. Ge, Xin Ye, Mingyu Zhu, Shenjun Senyei, Grant Lum, Lawrence Ehrlich, Barbara E. Qyang, Yibing TI Small molecule Wnt inhibitors enhance the efficiency of BMP-4-directed cardiac differentiation of human pluripotent stem cells SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Cardiomyocyte; Embryonic stem cell; Induced pluripotent stem cell; Cardiac differentiation; Optical recording ID HUMAN SOMATIC-CELLS; DEFINED FACTORS; CARDIOMYOCYTES; MYOCYTES; HEART; FIBROBLASTS; INDUCTION; MESODERM; RENEWAL; DEVELOP AB Human induced pluripotent stem (iPS) cells potentially provide a unique resource for generating patient-specific cardiomyocytes to study cardiac disease mechanisms and treatments. However, existing approaches to cardiomyocyte production from human iPS cells are inefficient, limiting the application of iPS cells in basic and translational cardiac research. Furthermore, strategies to accurately record changes in iPS cell-derived cardiomyocyte action potential duration (APD) are needed to monitor APD-related cardiac disease and for rapid drug screening. We examined whether modulation of the bone morphogenetic protein 4 (BMP-4) and Wnt/beta-catenin signaling pathways could induce efficient cardiac differentiation of human iPS cells. We found that early treatment of human iPS cells with BMP-4 followed by late treatment with small molecule Wnt inhibitors led to a marked increase in production of cardiomyocytes compared to existing differentiation strategies. Using immunocytochemical staining and real-time intracellular calcium imaging, we showed that these induced cardiomyocytes expressed typical sarcomeric markers, exhibited normal rhythmic Ca2+ transients, and responded to both beta-adrenergic and electric stimulation. Furthermore, human iPS cell-derived cardiomyocytes demonstrated characteristic changes in action potential duration in response to cardioactive drugs procainamide and verapamil using voltage-sensitive dye-based optical recording. Thus, modulation of the BMP-4 and Wnt signaling pathways in human iPS cells leads to highly efficient production of cardiomyocytes with typical electrophysiological function and pharmacologic responsiveness. The use of human iPS cell-derived cardiomyocytes and the application of calcium-and voltage-sensitive dyes for the direct, rapid measurement of iPS cell-derived cardiomyocyte activity promise to offer attractive platforms for studying cardiac disease mechanisms and therapeutics. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Ren, Yongming; Lee, Min Young; Amos, Peter J.; Ge, Xin; Senyei, Grant; Qyang, Yibing] Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06520 USA. [Schliffke, Simon; Paavola, Jere; Ehrlich, Barbara E.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. [Schliffke, Simon] Univ Med Ctr Hamburg Eppendorf, Dept Anat Expt Morphol 2, Hamburg, Germany. [Paavola, Jere] Minerva Fdn, Inst Med Res, Helsinki 00290, Finland. [Ye, Mingyu] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. [Zhu, Shenjun] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Lum, Lawrence] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. [Qyang, Yibing] Yale Univ, Yale Stem Cell Ctr, New Haven, CT 06520 USA. RP Qyang, YB (reprint author), Yale Univ, Sch Med, Yale Stem Cell Ctr, Sect Cardiovasc Med, 300 George St,Room 773A, New Haven, CT 06510 USA. EM yibing.qyang@yale.edu FU Yale startup fund; Connecticut Stem Cell [09SCAYALE10]; NIH [1K02HL101990-01, UL1 RR024139, 5 T32 HL007950, 1R01GM076398-01, DK57751, DK061747]; Finnish Foundation for Cardiovascular Research; Welch Foundation [I-1665] FX This work was supported by the Yale startup fund, the Connecticut Stem Cell 09SCAYALE10, NIH 1K02HL101990-01 and UL1 RR024139 (YQ), NIH 5 T32 HL007950 (PJ), the Finnish Foundation for Cardiovascular Research (JP), Welch Foundation I-1665 and NIH 1R01GM076398-01 (LL), and NIH DK57751 and DK061747 (BEE). NR 39 TC 67 Z9 70 U1 2 U2 30 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2011 VL 51 IS 3 BP 280 EP 287 DI 10.1016/j.yjmcc.2011.04.012 PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 812TI UT WOS:000294315400002 PM 21569778 ER PT J AU Kelly, PJ Lin, YB Yu, AYC Ropper, AE Nguyen, PL Marcus, KJ Hacker, FL Weiss, SE AF Kelly, Paul J. Lin, Yijie Brittany Yu, Alvin Y. C. Ropper, Alexander E. Nguyen, Paul L. Marcus, Karen J. Hacker, Fred L. Weiss, Stephanie E. TI Linear accelerator-based stereotactic radiosurgery for brainstem metastases: the Dana-Farber/Brigham and Women's Cancer Center experience SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Stereotactic radiosurgery; Brainstem; Metastasis; Linear accelerator ID GAMMA-KNIFE RADIOSURGERY; THERAPEUTIC IRRADIATION; RADIATION-THERAPY; TUMORS; TOLERANCE; SURVIVAL; INJURY; TRIAL AB To review the safety and efficacy of linear accelerator-based stereotactic radiosurgery (SRS) for brainstem metastases. We reviewed all patients with brain metastases treated with SRS at DF/BWCC from 2001 to 2009 to identify patients who had SRS to a single brainstem metastasis. Overall survival and freedom-from-local failure rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. A total of 24 consecutive patients with brainstem metastases had SRS. At the time of SRS, 21/24 had metastatic lesions elsewhere within the brain. 23/24 had undergone prior WBRT. Primary diagnoses included eight NSCLC, eight breast cancer, three melanoma, three renal cell carcinoma and two others. Median dose was 13 Gy (range, 8-16). One patient had fractionated SRS 5 Gy x5. Median target volume was 0.2 cc (range, 0.02-2.39). The median age was 57 years (range, 42-92). Follow-up information was available in 22/24 cases. At the time of analysis, 18/22 patients (82%) had died. The median overall survival time was 5.3 months (range, 0.8-21.1 months). The only prognostic factor that trended toward statistical significance for overall survival was the absence of synchronous brain metastasis at the time of SRS; 1-year overall survival was 31% with versus 67% without synchronous brain metastasis (log rank P = 0.11). Non-significant factors included primary tumor histology and status of extracranial disease (progressing vs. stable/absent). Local failure occurred in 4/22 cases (18%). Actuarial freedom from local failure for all cases was 78.6% at 1 year. RTOG grade 3 toxicities were recorded in two patients (ataxia, confusion). Linac-based SRS for small volume brainstem metastases using a median dose of 13 Gy is associated with acceptable local control and low morbidity. C1 [Kelly, Paul J.; Nguyen, Paul L.; Marcus, Karen J.; Hacker, Fred L.; Weiss, Stephanie E.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. [Lin, Yijie Brittany; Yu, Alvin Y. C.] Harvard Univ, Sch Med, Boston, MA USA. [Ropper, Alexander E.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Kelly, PJ (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 75 Francis St ASB1-L2, Boston, MA 02115 USA. EM pkelly@lroc.harvard.edu OI Hacker, Fred/0000-0001-7535-7598 NR 25 TC 14 Z9 15 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2011 VL 104 IS 2 BP 553 EP 557 DI 10.1007/s11060-010-0514-0 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 812BX UT WOS:000294263800015 PM 21213018 ER PT J AU Barnard, ZR Agarwalla, PK Jeyaretna, DS Farrell, CJ Gerstner, ER Tian, D Curry, WT AF Barnard, Zachary Rollins Agarwalla, Pankaj Kumar Jeyaretna, Deva Sanjeeva Farrell, Christopher James Gerstner, Elizabeth Robins Tian, Di Curry, William Thomas, Jr. TI Sporadic primary malignant intracerebral nerve sheath tumors: case report and literature review SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE MINST; MPNST; Schwannoma; Spindle cell neoplasm ID NEUROFIBROMATOSIS TYPE-1; SCHWANNOMA AB We report the case of a seventy-five year old woman with a sporadic primary malignant intracerebral nerve sheath tumor (MINST). These tumors fall within the spectrum of malignant peripheral nerve sheath tumors (MPNST) but confirming the diagnosis of a MINST can be difficult due to its rarity and unusual intraparenchymal location. Radiographically, MINST's mimic malignant glioma and should be considered in the differential diagnosis of enhancing cerebral lesions. In this report, we present a comprehensive panel of histological, immunohistochemical, ultrastructural, and genetic considerations that may be used to diagnosis MINST based on their similarities to MPNSTs and brain parenchyma location. C1 [Barnard, Zachary Rollins; Agarwalla, Pankaj Kumar; Jeyaretna, Deva Sanjeeva; Farrell, Christopher James; Curry, William Thomas, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Neurosurg, Boston, MA 02114 USA. [Gerstner, Elizabeth Robins; Curry, William Thomas, Jr.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Ctr Canc, Boston, MA 02114 USA. [Gerstner, Elizabeth Robins] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Tian, Di] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Barnard, ZR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Neurosurg, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM zbarnard@gmail.com NR 20 TC 6 Z9 6 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD SEP PY 2011 VL 104 IS 2 BP 605 EP 610 DI 10.1007/s11060-011-0531-7 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 812BX UT WOS:000294263800023 PM 21327709 ER PT J AU DesRoches, CM Miralles, P Buerhaus, P Hess, R Donelan, K AF DesRoches, Catherine M. Miralles, Paola Buerhaus, Peter Hess, Robert Donelan, Karen TI Health Information Technology in the Workplace Findings From a 2010 National Survey of Registered Nurses SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID NURSING DOCUMENTATION; MEANINGFUL-USE; RECORDS; CARE; NURSES; SYSTEMS; IMPACT; PHYSICIANS; EFFICIENCY; QUALITY AB The objective of this study was to examine RNs' experiences with health information technology (HIT) and their perceptions of the effect of this technology on quality of care and daily work. The adoption and use of HIT are expected to increase substantially over the next 5 years because of policy efforts at the federal and state levels. Given the size of the RN workforce and their critical role in healthcare delivery, their experiences with HIT could help adoption efforts. The method used was a nationally representative survey of 1500 nurses with a 56% response rate. Findings suggest wide variation in the availability of HIT functionality, with functions more likely available to hospital RNs. Overall, RNs perceived the effect of these technologies on quality of care and their daily work as positive. Ensuring that HIT systems are relevant to and usable for RNs will be a critical component in achieving the meaningful use of these systems. C1 [DesRoches, Catherine M.] Math Policy Res, Cambridge, MA 02139 USA. [Miralles, Paola; Donelan, Karen] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Donelan, Karen] Harvard Univ, Sch Med, Boston, MA USA. [Buerhaus, Peter] Vanderbilt Univ, Med Ctr, Ctr Interdisciplinary Hlth Workforce Studies, Nashville, TN USA. [Hess, Robert] Gannett Healthcare Grp, Global Programming, Gannett Educ, Hoffman Estates, IL USA. RP DesRoches, CM (reprint author), Math Policy Res, 955 Massachusetts Ave,Suite 801, Cambridge, MA 02139 USA. EM cdesroches@mathematica-mpr.com FU Johnson and Johnson Campaign for Nursing's Future; Gannett Healthcare Group FX This study was funded by an unrestricted grant from the Johnson and Johnson Campaign for Nursing's Future and by the Gannett Healthcare Group. Johnson and Johnson played no role in the design and conduct of the study, analysis and interpretation of results, and preparation or approval of the article. NR 29 TC 5 Z9 5 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD SEP PY 2011 VL 41 IS 9 BP 357 EP 364 DI 10.1097/NNA.0b013e31822a7165 PG 8 WC Nursing SC Nursing GA 814OH UT WOS:000294465700006 PM 21881441 ER PT J AU Goudreau, KA Ortman, MI Moore, JD Aldredge, L Helland, MK Fernandes, LA Gibson, S AF Goudreau, Kelly A. Ortman, Maria Idelsi Moore, Jean D. Aldredge, Lakshi Helland, Mary K. Fernandes, Laurie A. Gibson, Steve TI A Nurse Practitioner Residency Pilot Program A Journey of Learning SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article AB A collaborative team developed a yearlong residency experience for a staff nurse transitioning to a nurse practitioner role in the Veterans Affairs system. To assist others desiring to provide support, networking, and infrastructure to those transitioning into new roles, the authors discuss strengths and weaknesses of the pilot and lessons learned related to defining trainee versus resident, credentialing and privileging, and specific mentoring needed for the role of the nurse practitioner. C1 [Goudreau, Kelly A.; Moore, Jean D.] Portland VA Med Ctr, Nursing Primary Care Div, Portland, OR 97239 USA. [Fernandes, Laurie A.] Portland VA Med Ctr, Operat Care Div, Portland, OR 97239 USA. [Gibson, Steve] Portland VA Med Ctr, Clin Board Primary Care, Portland, OR 97239 USA. [Gibson, Steve] Portland VA Med Ctr, N Coast Clin, Portland, OR 97239 USA. [Gibson, Steve] Portland VA Med Ctr, Hillsboro Clin, Portland, OR 97239 USA. RP Goudreau, KA (reprint author), Portland VA Med Ctr, Nursing Primary Care Div, P2EDUC,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Kelly.Goudreau@va.gov NR 17 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD SEP PY 2011 VL 41 IS 9 BP 382 EP 387 DI 10.1097/NNA.0b013e31822a7315 PG 6 WC Nursing SC Nursing GA 814OH UT WOS:000294465700010 PM 21881445 ER PT J AU Wang, L Tsai, M Manson, JE Djousse, L Gaziano, JM Buring, JE Sesso, HD AF Wang, Lu Tsai, Michael Manson, JoAnn E. Djousse, Luc Gaziano, J. Michael Buring, Julie E. Sesso, Howard D. TI Erythrocyte Fatty Acid Composition Is Associated with the Risk of Hypertension in Middle-Aged and Older Women SO JOURNAL OF NUTRITION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR-DISEASE; ADIPOSE-TISSUE; BLOOD-PRESSURE; NUTRITIONAL FACTORS; PRIMARY PREVENTION; HEART; PLASMA; HEALTH; CANCER AB Experimental studies have suggested different effects of various fats on blood pressure. However, epidemiologic evidence of these relations remains limited and inconsistent. We therefore assessed the association of fatty acid (FA) composition in erythrocyte membranes with the risk of hypertension. We selected 516 cases of incident hypertension and 516 matched controls during 12.9 y of follow-up in the Women's Health Study. Erythrocyte FA was measured in baseline bloods using GC. After controlling matching factors and lifestyle factors, erythrocyte SFA showed a positive association, whereas total cis PUFA, cis (n-3) PUFA, and the ratio of PUFA:SFA (PS ratio) showed an inverse association with the risk of hypertension. The multivariable IRA of hypertension across the increasing quartiles of erythrocyte FA subtypes were 1.00, 1.19, 1.44, and 1.76 for total SFA; 1.00, 0.84, 0.88, and 0.56 for total cis PUFA; 1.00, 0.87, 0.66, and 0.65 for cis (n-3) PUFA; and 1.00, 0.99, 0.70, and 0.51 for the PS ratio. After further adjusting for obesity-related metabolic factors, these associations were attenuated and remained significant only for the PS ratio. cis MUFA, cis (n-6) PUFA, and trans unsaturated FA in erythrocyte membranes were not associated with the risk of hypertension. Our study showed that FA composition in erythrocyte membranes is associated with the risk of hypertension in middle-aged and older women. However, after controlling for obesity-related metabolic factors, the associations remained significant only for the PS ratio. J. Nutr. 141: 1691-1697, 2011. C1 [Wang, Lu; Manson, JoAnn E.; Gaziano, J. Michael; Buring, Julie E.; Sesso, Howard D.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Djousse, Luc; Gaziano, J. Michael; Buring, Julie E.; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Tsai, Michael] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Manson, JoAnn E.; Buring, Julie E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Djousse, Luc; Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Djousse, Luc; Gaziano, J. Michael] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. RP Wang, L (reprint author), Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. EM luwang@rics.bwh.harvard.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU AHA [0735390N]; NIH, Bethesda, MD [CA047988, HL043851, HL080467] FX Supported by a scientist development grant funded by the AHA (0735390N) and research grants CA047988, HL043851, and HL080467 from the NIH, Bethesda, MD. These grants provided funding for study conduct, data collection, and data analyses. NR 35 TC 8 Z9 8 U1 0 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD SEP PY 2011 VL 141 IS 9 BP 1691 EP 1697 DI 10.3945/jn.111.138867 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 815KC UT WOS:000294523500016 PM 21734059 ER PT J AU Courtwright, AM Laughon, MM Doron, MW AF Courtwright, A. M. Laughon, M. M. Doron, M. W. TI Lethality begets lethality Reply SO JOURNAL OF PERINATOLOGY LA English DT Letter ID MANAGEMENT; TRISOMY-18 C1 [Courtwright, A. M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Laughon, M. M.; Doron, M. W.] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. RP Courtwright, AM (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM mdoron@unc.edu NR 2 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD SEP PY 2011 VL 31 IS 9 BP 631 EP 632 DI 10.1038/jp.2011.55 PG 3 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 814MW UT WOS:000294460600012 ER PT J AU Lysaght, AC Kao, SY Paulo, JA Merchant, SN Steen, H Stankovic, KM AF Lysaght, Andrew C. Kao, Shyan-Yuan Paulo, Joao A. Merchant, Saumil N. Steen, Hanno Stankovic, Konstantina M. TI Proteome of Human Perilymph SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE perilymph; proteomics; mass spectrometry; human; vestibular schwannoma ID HUMAN PLASMA PROTEOME; INNER-EAR; CEREBROSPINAL-FLUID; HEYMANN NEPHRITIS; HEARING-LOSS; VESTIBULAR SCHWANNOMAS; ACOUSTIC NEURINOMA; MASS-SPECTROMETRY; GUINEA-PIG; LOCALIZATION AB Current diagnostic tools limit a clinician's ability to discriminate between many possible causes of sensorineural hearing loss. This constraint leads to the frequent diagnosis of the idiopathic condition, leaving patients without a clear prognosis and only general treatment options. As a first step toward developing new diagnostic tools and improving patient care, we report the first use of liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to map the proteome of human perilymph. Using LC-MS/MS, we analyzed four samples, two collected from patients with vestibular schwannoma (VS) and two from patients undergoing cochlear implantation (CI). For each cohort, one sample contained pooled specimens collected from five patients and the second contained a specimen obtained from a single patient. Of the 271 proteins identified with high confidence among the samples, 71 proteins were common in every sample and used to conservatively define the proteome of human perilymph. Comparison to human cerebrospinal fluid and blood plasma, as well as murine perilymph, showed significant similarity in protein content across fluids; however, a quantitative comparison was not possible. Fifteen candidate biomarkers of VS were identified by comparing VS and CI samples. This list will be used in future investigations targeted at discriminating between VS tumors associated with good versus poor hearing. C1 [Lysaght, Andrew C.; Merchant, Saumil N.; Stankovic, Konstantina M.] Harvard & MIT, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. [Lysaght, Andrew C.; Kao, Shyan-Yuan; Merchant, Saumil N.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Paulo, Joao A.; Steen, Hanno] Harvard Univ, Sch Med, Childrens Hosp Boston, Prote Ctr, Boston, MA 02115 USA. [Paulo, Joao A.; Steen, Hanno] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pathol, Boston, MA 02115 USA. [Paulo, Joao A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Merchant, Saumil N.; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Stankovic, KM (reprint author), Harvard & MIT, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. EM konstantina_stankovic@meei.harvard.edu FU American Otologic Society (AOS); Massachusetts Life Sciences Center (MLSC); NIDCD [T32 DC00038, K08 DC010419]; NIH [U24 DC008559]; Harvard Medical School FX We thank Dr. Jose Fayad for the kind donation of five perilymph specimens. This project was supported by the American Otologic Society (AOS), Massachusetts Life Sciences Center (MLSC), NIDCD grants T32 DC00038 and K08 DC010419, NIH grant U24 DC008559, and Shore Fellowship at Harvard Medical School. This work is solely the responsibility of the authors and does not necessarily represent the official views of the AOS, MLSC, NIDCD, or NIH. NR 36 TC 14 Z9 15 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD SEP PY 2011 VL 10 IS 9 BP 3845 EP 3851 DI 10.1021/pr200346q PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 814JN UT WOS:000294446600001 PM 21740021 ER PT J AU House, E AF House, Ellen TI The Black Cauldron (Chronicles of Prydain, Book 2). SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [House, Ellen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP House, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ehouse@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2011 VL 50 IS 9 BP 951 EP 955 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 815FP UT WOS:000294511800015 ER PT J AU House, E AF House, Ellen TI The Book of Three (Chronicles of Prydain, Book 1) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [House, Ellen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP House, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ehouse@partners.org NR 1 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2011 VL 50 IS 9 BP 951 EP 955 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 815FP UT WOS:000294511800014 ER PT J AU House, E AF House, Ellen TI The Castle of Llyr (Chronicles of Prydain, Book 3) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [House, Ellen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP House, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ehouse@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2011 VL 50 IS 9 BP 952 EP 955 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 815FP UT WOS:000294511800016 ER PT J AU House, E AF House, Ellen TI Taran Wanderer (Chronicles of Prydain, Book 4). SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [House, Ellen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP House, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ehouse@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2011 VL 50 IS 9 BP 952 EP 955 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 815FP UT WOS:000294511800017 ER PT J AU House, E AF House, Ellen TI The High King (Chronicles of Prydain, Book 5) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [House, Ellen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP House, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ehouse@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2011 VL 50 IS 9 BP 952 EP 955 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 815FP UT WOS:000294511800018 ER PT J AU D'Avolio, LW Nguyen, TM Goryachev, S Fiore, LD AF D'Avolio, Leonard W. Nguyen, Thien M. Goryachev, Sergey Fiore, Louis D. TI Automated concept-level information extraction to reduce the need for custom software and rules development SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID DE-IDENTIFICATION AB Objective Despite at least 40 years of promising empirical performance, very few clinical natural language processing (NLP) or information extraction systems currently contribute to medical science or care. The authors address this gap by reducing the need for custom software and rules development with a graphical user interface-driven, highly generalizable approach to concept-level retrieval. Materials and methods A 'learn by example' approach combines features derived from open-source NLP pipelines with open-source machine learning classifiers to automatically and iteratively evaluate top-performing configurations. The Fourth i2b2/VA Shared Task Challenge's concept extraction task provided the data sets and metrics used to evaluate performance. Results Top F-measure scores for each of the tasks were medical problems (0.83), treatments (0.82), and tests (0.83). Recall lagged precision in all experiments. Precision was near or above 0.90 in all tasks. Discussion With no customization for the tasks and less than 5 min of end-user time to configure and launch each experiment, the average F-measure was 0.83, one point behind the mean F-measure of the 22 entrants in the competition. Strong precision scores indicate the potential of applying the approach for more specific clinical information extraction tasks. There was not one best configuration, supporting an iterative approach to model creation. Conclusion Acceptable levels of performance can be achieved using fully automated and generalizable approaches to concept-level information extraction. The described implementation and related documentation is available for download. C1 [D'Avolio, Leonard W.; Nguyen, Thien M.; Goryachev, Sergey; Fiore, Louis D.] VA Boston Healthcare Syst, MAVERIC, Cooperat Studies Coordinating Ctr, Boston, MA 02130 USA. [D'Avolio, Leonard W.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [D'Avolio, Leonard W.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [D'Avolio, Leonard W.] Harvard Univ, Sch Med, Boston, MA USA. [Fiore, Louis D.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Fiore, Louis D.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP D'Avolio, LW (reprint author), VA Boston Healthcare Syst, MAVERIC MAV 151, 150 S Huntington Ave, Boston, MA 02130 USA. EM leonard.davolio@va.gov FU Veterans Affairs Cooperative Studies Program; Consortium for Health Informatics Research (CHIR) [HIR 09-007] FX This work was supported by Veterans Affairs Cooperative Studies Program as well as the Veterans Affairs Health Services Research and Development grant, Consortium for Health Informatics Research (CHIR), grant # HIR 09-007. NR 30 TC 24 Z9 24 U1 4 U2 11 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP PY 2011 VL 18 IS 5 BP 607 EP 613 DI 10.1136/amiajnl-2011-000183 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 816AV UT WOS:000294572000013 PM 21697292 ER PT J AU Kimball, TA Barz, K Dimond, KR Edwards, JM Nehler, MR AF Kimball, Traci A. Barz, Ken Dimond, Kelly R. Edwards, James M. Nehler, Mark R. TI Efficiency of the kidney disease outcomes quality initiative guidelines for preemptive vascular access in an academic setting SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Western-Vascular-Society CY SEP 25-28, 2010 CL Sunriver, OR SP Western Vasc Soc ID RANDOMIZED CONTROLLED-TRIAL; PREOPERATIVE NONINVASIVE EVALUATION; ARTERIOVENOUS-FISTULA MATURATION; ABDOMINAL AORTIC-ANEURYSMS; 1ST-TIME DIALYSIS ACCESS; VEIN GRAFT FAILURE; HEMODIALYSIS ACCESS; AUTOLOGOUS FISTULAS; NATURAL-HISTORY; INCREASING USE AB Background: The National Kidney Foundation-Kidney Diseases Outcomes Quality Initiative (KDOQI) for vascular access guidelines state that patients with late-stage chronic kidney disease (CKD) should undergo native arteriovenous fistula (AVF) creation at least 6 months before anticipated start of hemodialysis (HD) treatments to obviate the need for other vascular access types, such as grafts or central catheters. Objective: The objective of this study was to determine the incidence of HD, the functional patency, and associated morbidity of AVFs in patients with late-stage CKD placed according to KDOQI. Methods: Consecutive patients with late-stage CKD who underwent AVF creation using KDOQI guidelines for anatomy between January 2003 and December 2007 at two tertiary academic centers were retrospectively evaluated. Baseline demographics, AVF type, and clinical comorbidities were recorded. Patients were stratified into one of four groups (groups A-D) over the follow-up course based on two end points: patency of their AVF and whether or not they began HD. The ideal primary outcome was AVF maturation and use for HD (group A; cumulative functional patency). Other outcomes included AVF patency but no HD (group B), HD with AVF failure (group C), or no HD and AVF abandonment (ie, death, refused hemodialysis, kidney transplant, or fistula failure; group D). Secondary outcomes were time to first cannulation, complications, and secondary interventions. Results: AVFs were created (46% forearm and 54% upper arm) in 150 patients with CKD (85% men, median age 63 years old). At a median follow-up of 10 months, 74 patients (49%) were receiving HD and of these, 48 patients (65%) were using their AVF (group A), whereas 26 patients (35%) were not due to fistula failure (group C). Thirty-four patients (23%) never initiated HD treatments, but had a viable AVF (group B), and 42 patients (28%) never initiated HD and abandoned their AVF (group D). Overall, AVE abandonment was 51%. Mean maturation time of all AVFs successfully cannulated was 285 days (range, 30-1265 days). Complications encountered were maturation failure for cannulation (15%), focal stenosis requiring intervention (13%), inadequate flows on FED (9%), steal syndrome (9%), and thrombosis (8%). Cumulative functional patency for all AVFs was 19% and 27% at 6 and 12 months, respectively, with a mean number of two interventions per AVF (range, 1-10). Mortality during the study was 23%. Conclusion: Despite successful creation and maturation of a preemptive AVF in nearly two-thirds of patients who started HD during the follow-up and given the following observations: the high overall mortality of the population, the morbidity and costs in secondary procedures of AVF creation, and the high incidence of abandonment, it is unclear if this strategy would demonstrate a benefit in a randomized trial when compared to other access strategies. (J Vase Surg 2011;54:760-6.) C1 [Kimball, Traci A.; Dimond, Kelly R.; Nehler, Mark R.] Univ Colorado, Vasc Surg Sect, Denver, CO 80202 USA. [Barz, Ken] Colorado Prevent Ctr, Denver, CO USA. [Edwards, James M.] Portland VA Med Ctr, Portland, OR USA. RP Nehler, MR (reprint author), Univ Colorado Denver, 12631 E 17th Ave,Room L15-5415, Aurora, CO 80045 USA. EM nehler@ucdenver.edu NR 29 TC 17 Z9 19 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2011 VL 54 IS 3 BP 760 EP 766 DI 10.1016/j.jvs.2011.03.006 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 815DC UT WOS:000294505300022 PM 21703804 ER PT J AU Grenon, SM Reilly, LM Ramaiah, VG AF Grenon, S. Marlene Reilly, Linda M. Ramaiah, Ventakesh G. TI Technical endovascular highlights for crossing the difficult aortic bifurcation SO JOURNAL OF VASCULAR SURGERY LA English DT Article AB Effective endovascular treatment requires successful vascular access to reach the targeted lesion. When the targeted lesion is infrainguinal in location, the vascular access options include the ipsilateral antegrade femoral approach, the contralateral retrograde femoral approach, or the transbrachial approach. The contralateral retrograde femoral route remains the most commonly used approach but may be challenging, particularly in the settings of a scarred groin or a difficult aortic bifurcation. The purpose of this article is to provide technical tips for the challenges encountered in obtaining contralateral femoral access for peripheral interventions with a difficult aortic bifurcation. (J Vasc Surg 2011;54:893-6.) C1 [Grenon, S. Marlene; Reilly, Linda M.] Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA. [Grenon, S. Marlene; Reilly, Linda M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ramaiah, Ventakesh G.] Arizona Heart Inst, Phoenix, AZ USA. RP Grenon, SM (reprint author), Univ Calif San Francisco, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2011 VL 54 IS 3 BP 893 EP 896 DI 10.1016/j.jvs.2011.03.268 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 815DC UT WOS:000294505300045 PM 21664094 ER PT J AU Aranson, NJ Patel, VI Ergul, E LaMuraglia, GM Kwolek, CJ Cambria, RP Conrad, MF AF Aranson, Nathan J. Patel, Virendra I. Ergul, Emel LaMuraglia, Glenn M. Kwolek, Christopher J. Cambria, Richard P. Conrad, Mark F. TI Chronic Kidney Disease Class Predicts Mortality After Abdominal Aortic Aneurysm Repair in Propensity-Matched Cohorts from the Medicare Population SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract C1 [Aranson, Nathan J.; Patel, Virendra I.; Ergul, Emel; LaMuraglia, Glenn M.; Kwolek, Christopher J.; Cambria, Richard P.; Conrad, Mark F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. OI Aranson, Nathan/0000-0001-8833-4643 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2011 VL 54 IS 3 BP 916 EP 916 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 815DC UT WOS:000294505300054 ER PT J AU Zhang, Y Thamer, M Kaufman, JS Cotter, DJ Hernan, MA AF Zhang, Yi Thamer, Mae Kaufman, James S. Cotter, Dennis J. Hernan, Miguel A. TI High doses of epoetin do not lower mortality and cardiovascular risk among elderly hemodialysis patients with diabetes SO KIDNEY INTERNATIONAL LA English DT Article DE cardiovascular outcomes; diabetes; epoetin; hemodialysis; marginal structural modeling; mortality ID CHRONIC KIDNEY-DISEASE; RECEIVING HEMODIALYSIS; ANEMIA; ERYTHROPOIETIN; OUTCOMES; TRIAL; HEMATOCRIT AB A randomized trial had suggested that high doses of erythropoiesis-stimulating agents (ESAs) might increase the risk of cardiovascular outcomes in predialysis diabetic patients. To evaluate this risk in diabetic patients receiving dialysis, we used data from 35,593 elderly Medicare patients on hemodialysis in the US Renal Data System of whom 19,034 were diabetic. A pooled logistic model was used to estimate the monthly probability of mortality and a composite cardiovascular end point. Inverse probability weighting was used to adjust for measured time-dependent confounding by indication, estimated separately for diabetic and non-diabetic cohorts. The adjusted 9-month mortality risk, significantly different between an ESA dose of 45,000 and 15,000U/week, was 13% among diabetics and 5% among non-diabetics. In diabetic patients, the hazard ratio (HR) for more than 40,000U/week was 1.32 for all-cause mortality and 1.26 for a composite end point of death and cardiovascular events compared with patients receiving 20,000 to 30,000 U/week. The corresponding HRs in nondiabetic patients were 1.06 and 1.10, respectively. A smaller effect of dose was found in non-diabetic patients. Thus, higher ESA doses, which are often necessary to achieve high hemoglobin levels, are not beneficial, and possibly harmful, to diabetic patients receiving dialysis. Our findings support a Food and Drug Administration advisory recommending that the lowest possible ESA dose be used to treat hemodialysis patients. Kidney International (2011) 80, 663-669; doi: 10.1038/ki.2011.188; published online 22 June 2011 C1 [Zhang, Yi; Thamer, Mae; Cotter, Dennis J.] Med Technol & Practice Patterns Inst, Bethesda, MD 20814 USA. [Kaufman, James S.] VA Boston Healthcare Syst, Boston, MA USA. [Hernan, Miguel A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Cotter, DJ (reprint author), Med Technol & Practice Patterns Inst, 4733 Bethesda Ave,Suite 510, Bethesda, MD 20814 USA. EM dcott@mtppi.org FU US National Institutes of Health [R01-DK066011-01A2, R01-HL080644-01]; US Agency for Healthcare Research and Quality [R21-HS19513-01] FX The study was supported by the US National Institutes of Health Grants R01-DK066011-01A2 and R01-HL080644-01, and the US Agency for Healthcare Research and Quality Grant R21-HS19513-01. The data reported here have been supplied by the US Renal Data System. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as the official policy or interpretation of the US government. NR 25 TC 24 Z9 25 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2011 VL 80 IS 6 BP 663 EP 669 DI 10.1038/ki.2011.188 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 814ML UT WOS:000294458900014 PM 21697811 ER PT J AU McDuff, FKE Hook, CE Tooze, RM Huntly, BJ Pandolfi, PP Turner, SD AF McDuff, Fiona K. E. Hook, C. Elizabeth Tooze, Reuben M. Huntly, Brian J. Pandolfi, Pier Paolo Turner, Suzanne D. TI Determining the contribution of NPM1 heterozygosity to NPM-ALK-induced lymphomagenesis SO LABORATORY INVESTIGATION LA English DT Article DE ALCL; lymphoma; mouse model; NPM-ALK; NPM1 ID LYMPHOID MALIGNANCY; CELL LYMPHOMAS; MOUSE MODELS; MICE; NUCLEOPHOSMIN; KINASE AB Heterozygous expression of Nucleophosmin (NPM1) predisposes to hematological malignancies in the mouse and cooperates with Myc in lymphomagenesis. NPM1 is therefore regarded as a haploinsufficient tumor suppressor. Heterozygous loss of NPM1 occurs as a result of the t(2;5), which generates the oncogenic fusion tyrosine kinase, NPM-anaplastic lymphoma kinase (ALK), a molecule underlying the pathogenesis of anaplastic large cell lymphoma (ALCL). Given the aforementioned role of NPM1 as a tumor suppressor, we hypothesized that NPM1 heterozygosity would cooperate with NPM-ALK in lymphomagenesis. In the event, we observed no difference in tumor latency, incidence or phenotype in NPM-ALK-transgenic mice heterozygous for NPM1 relative to transgenic mice expressing both NPM1 alleles. We propose that although the t(2;5) simultaneously reduces NPM1 allelic dosage and creates the NPM-ALK fusion protein, the two events do not cooperate in the pathogenesis of ALCL in our mouse model. These data indicate that a tumor-suppressive role for NPM1 may depend on cellular and/or genetic context. Laboratory Investigation (2011) 91, 1298-1303; doi: 10.1038/labinvest.2011.96; published online 27 June 2011 C1 [McDuff, Fiona K. E.; Turner, Suzanne D.] Univ Cambridge, Addenbrookes Hosp, Div Mol Histopathol, Dept Pathol, Cambridge CB2 0QQ, England. [Hook, C. Elizabeth] Addenbrookes Hosp, Dept Histopathol, Cambridge CB2 2QQ, England. [Tooze, Reuben M.] Univ Leeds, Leeds Inst Mol Med, Leeds, W Yorkshire, England. [Huntly, Brian J.] Univ Cambridge, Dept Haematol, Cambridge CB2 0QQ, England. [Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Canc Genet Program,Dept Med & Pathol, Boston, MA 02215 USA. RP Turner, SD (reprint author), Univ Cambridge, Addenbrookes Hosp, Div Mol Histopathol, Dept Pathol, Lab Block Level 3,Box 231,Hills Rd, Cambridge CB2 0QQ, England. EM sdt36@cam.ac.uk RI Turner, Suzanne/K-4405-2013 OI Turner, Suzanne/0000-0002-8439-4507 FU Cancer Research UK [C19666]; Wellcome Trust FX This work was supported by Cancer Research UK (C19666 to SDT) and the Wellcome Trust (studentship to FKEM). SDT is a Leukaemia and Lymphoma Research Bennett Fellow (07006 to SDT), RT is a Cancer Research UK Senior Clinical Fellow and BJH is a Medical Research Council Senior Clinical Research Fellow. NR 12 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD SEP PY 2011 VL 91 IS 9 BP 1298 EP 1303 DI 10.1038/labinvest.2011.96 PG 6 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 814HZ UT WOS:000294440500004 ER PT J AU Barnes, DE Yaffe, K AF Barnes, Deborah E. Yaffe, Kristine TI The projected effect of risk factor reduction on Alzheimer's disease prevalence SO LANCET NEUROLOGY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; LATE-LIFE DEPRESSION; PHYSICAL-ACTIVITY; CARDIOVASCULAR-HEALTH; INCIDENT DEMENTIA; VASCULAR-DISEASE; BLOOD-PRESSURE; GLOBAL BURDEN; OLDER-ADULTS AB At present, about 33-9 million people worldwide have Alzheimer's disease (AD), and prevalence is expected to triple over the next 40 years. The aim of this Review was to summarise the evidence regarding seven potentially modifiable risk factors for AD: diabetes, midlife hypertension, midlife obesity, smoking, depression, cognitive inactivity or low educational attainment, and physical inactivity. Additionally, we projected the effect of risk factor reduction on AD prevalence by calculating population attributable risks (the percent of cases attributable to a given factor) and the number of AD cases that might be prevented by risk factor reductions of 10% and 25% worldwide and in the USA. Together, up to half of AD cases worldwide (17.2 million) and in the USA (2.9 million) are potentially attributable to these factors. A 10-25% reduction in all seven risk factors could potentially prevent as many as 1.1-3.0 million AD cases worldwide and 184000-492000 cases in the USA. C1 [Barnes, Deborah E.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Barnes, Deborah E.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Barnes, DE (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement Sreet,151R, San Francisco, CA 94121 USA. EM deborah.barnes@ucsf.edu FU Alzheimer's Association; NARSAD; National Institute on Aging [K24 AG031155]; University of California, San Francisco, School of Medicine FX DEB is supported in part by the Alzheimer's Association, NARSAD, and the University of California, San Francisco, School of Medicine. KY is supported in part by the National Institute on Aging (K24 AG031155). NR 101 TC 588 Z9 601 U1 18 U2 155 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD SEP PY 2011 VL 10 IS 9 BP 819 EP 828 DI 10.1016/S1474-4422(11)70072-2 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 815NM UT WOS:000294532300010 PM 21775213 ER PT J AU Celli, JP Solban, N Liang, A Pereira, SP Hasan, T AF Celli, Jonathan P. Solban, Nicolas Liang, Alvin Pereira, Stephen P. Hasan, Tayyaba TI Verteporfin-Based Photodynamic Therapy Overcomes Gemcitabine Insensitivity in a Panel of Pancreatic Cancer Cell Lines SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE PDT; pancreatic ductal adenocarcinoma (PDAC); stroma; extracellular matrix; benzoporphyrin derivative (BPD) ID OVARIAN-CANCER; BPD-MA; STROMAL BIOLOGY; IN-VITRO; APOPTOSIS; BCL-2; INHIBITOR; CARCINOMA; TUMORS; MODEL AB Background and Objective: Pancreatic cancer is notoriously difficult to treat and resistant to virtually all therapeutics including gemcitabine, the standard front line agent for palliative chemotherapy. Early clinical studies point to a potential role for photodynamic therapy (PDT) in the management of this deadly disease. Here we examine PDT with verteporfin for treatment of cells that are nonresponsive to gemcitabine and identify intracellular and extracellular factors that govern sensitivity to each modality. Study Design: Using MTS we assess cytotoxicity of verteporfin-PDT in gemcitabine-treated nonresponsive populations from a panel of five pancreatic cancer cell lines representing a range of tumor histopathology and origin. We conduct Western blots for pro-/antiapoptotic proteins bax and Bcl-XL to identify factors relevant to PDT and gemcitabine sensitivity. To examine the role of extracellular matrix influences we compare response to each modality in traditional cell culture conditions and cells grown on a laminin-rich basement membrane. Results: All cell lines have gemcitabine nonresponsive populations (17-33%) at doses up to 1 mM while moderate total verteporfin PDT doses (1-6 mu M J/cm(2)) produce nearly complete killing. Our data shows that cells that are nonresponsive to sustained gemcitabine incubation are sensitive to verteporfin PDT indicating that the latter is agnostic to gemcitabine sensitivity. Verteporfin-based PDT decreases Bcl-XL and increases the bax/Bcl-XL ratio toward a pro-apoptotic balance. Insensitivity to gemcitabine is increased in cells that are adherent to basement membrane relative to traditional tissue culture conditions. Conclusions: Collectively these results indicate the ability of verteporfin-based PDT to bypass intracellular and extracellular cues leading to gemcitabine resistance and point to the emerging role of this therapy for treatment of pancreatic cancer. Lasers Surg. Med. 43: 565-574, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Celli, Jonathan P.; Solban, Nicolas; Liang, Alvin; Hasan, Tayyaba] Harvard Univ, Wellman Ctr Photomed, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Pereira, Stephen P.] UCL, Inst Hepatol, London, England. RP Hasan, T (reprint author), Harvard Univ, Wellman Ctr Photomed, Massachusetts Gen Hosp, Sch Med, 40 Blossom St, Boston, MA 02114 USA. EM thasan@partners.org FU National Institutes of Health [P01CA084203-06] FX Contract grant sponsor: National Institutes of Health; Contract grant number: P01CA084203-06. NR 50 TC 38 Z9 38 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD SEP PY 2011 VL 43 IS 7 BP 565 EP 574 DI 10.1002/lsm.21093 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 811PA UT WOS:000294223300005 PM 22057484 ER PT J AU Klepac-Ceraj, V Patel, N Song, XQ Holewa, C Patel, C Kent, R Amiji, MM Soukos, NS AF Klepac-Ceraj, Vanja Patel, Niraj Song, Xiaoqing Holewa, Colleen Patel, Chitrang Kent, Ralph Amiji, Mansoor M. Soukos, Nikolaos S. TI Photodynamic Effects of Methylene Blue-Loaded Polymeric Nanoparticles on Dental Plaque Bacteria SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE dental plaque bacteria; methylene blue; polymeric nanoparticles; photodynamic therapy ID POLY(BETA-AMINO ESTER) NANOPARTICLES; TUMOR-TARGETED DELIVERY; PH-SENSITIVE SYSTEM; HYDROPHOBIC DRUGS; IN-VITRO; THERAPY; BIOFILMS; RESISTANCE; PHOTOINACTIVATION; PHTHALOCYANINE AB Background and Objectives: Photodynamic therapy (PDT) is increasingly being explored for treatment of oral infections. Here, we investigate the effect of PDT on human dental plaque bacteria in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles with a positive or negative charge and red light at 665 nm. Study Design/Materials and Methods Subgingiva: Dental plaque samples were obtained from 14 patients with chronic periodontitis. Suspensions of plaque microorganisms from seven patients were sensitized with anionic, cationic PLGA nanoparticles (50 mg/ml equivalent to MB) or free MB (50 mg/ml) for 20 min followed by exposure to red light for 5 min with a power density of 100 mW/cm(2). Polymicrobial oral biofilms, which were developed on blood agar in 96-well plates from dental plaque inocula obtained from seven patients, were also exposed to PDT as above. Following the treatment, survival fractions were calculated by counting the number of colony-forming units. Results: The cationic MB-loaded nanoparticles exhibited greater bacterial phototoxicity in both planktonic and biofilm phase compared to anionic MB-loaded nanoparticles and free MB, but results were not significantly different (P > 0.05). Conclusion: Cationic MB-loaded PLGA nanoparticles have the potential to be used as carriers of MB for PDT systems. Lasers Surg. Med. 43: 600-606, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Klepac-Ceraj, Vanja; Patel, Niraj; Song, Xiaoqing; Holewa, Colleen; Patel, Chitrang; Soukos, Nikolaos S.] Forsyth Inst, Appl Mol Photomed Lab, Cambridge, MA 02142 USA. [Patel, Niraj; Amiji, Mansoor M.] Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Bouve Coll Hlth Sci, Boston, MA 02115 USA. [Kent, Ralph] Forsyth Inst, Dept Biostat, Cambridge, MA 02142 USA. RP Soukos, NS (reprint author), Forsyth Inst, Appl Mol Photomed Lab, 245 1st St, Cambridge, MA 02142 USA. EM nsoukos@forsyth.org RI Amiji, Mansoor/A-4365-2014; OI Amiji, Mansoor/0000-0001-6170-881X; Klepac-Ceraj, Vanja/0000-0001-5387-5706 FU NIDCR [R21-DE0-18782] FX Contract grant sponsor: NIDCR; Contract grant number: R21-DE0-18782. NR 36 TC 29 Z9 30 U1 1 U2 30 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD SEP PY 2011 VL 43 IS 7 BP 600 EP 606 DI 10.1002/lsm.21069 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 811PA UT WOS:000294223300009 PM 22057487 ER PT J AU Sakamoto, FH Doukas, AG Farinelli, WA Tannous, Z Su, Y Smith, NA Zurakowski, D Anderson, RR AF Sakamoto, Fernanda H. Doukas, Apostolos G. Farinelli, William A. Tannous, Zeina Su, Yao Smith, Nicholas A. Zurakowski, David Anderson, R. Rox TI Intracutaneous ALA Photodynamic Therapy: Dose-Dependent Targeting of Skin Structures SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE aminolevulinic acid; ALA; photochemotherapy; photodynamic therapy; PDT; injections; histology; dose-response relationship; drug ID BASAL-CELL CARCINOMA; PROTOPORPHYRIN-IX FLUORESCENCE; TOPICAL 5-AMINOLEVULINIC ACID; DELTA-AMINOLEVULINIC-ACID; MOUSE SKIN; PHARMACOKINETICS; TUMORS; INJECTION; ACCUMULATION; IRRADIATION AB Background: Photodynamic therapy (PDT) using topical aminolevulinic acid (ALA) depends on local drug uptake, metabolism to porphyrins, and depth of light penetration using different wavelengths. Topical ALA-PDT has limited depth of drug penetration. We studied induced porphyrin distribution and PDT after intradermal ALA administration using different drug concentrations followed by high-fluence red light irradiation. Materials and Methods: Intradermal injections (similar to 2 mm deep) of ALA concentrations from 0.0005% to 1% were studied in swine to evaluated porphyrin fluorescence before PDT and clinical and histological damage 24 hours after PDT. Porphyrin accumulation was measured by fluorescence microscopy of frozen section. PDT was performed 3 hours after intradermal injections using a 635 nm LED array at a fluence of 200 J/cm(2). Skin responses to PDT were observed grossly and by histology (blind evaluation). Results: Intradermal ALA caused porphyrin accumulation in epidermis, hair follicles (HF), sebaceous glands (SG), sweat glands (eccrine glands, EG and apocrine glands, AG), and subcutaneous fat. Significant differences of fluorescence intensity were observed between different skin structures (P < 0.05), but there was no significant difference comparing HF to SG; epidermis with either HF or SG; and dermis with fat (P > 0.05). Intradermal ALA is potent. ALA concentrations >= 0.25% followed by red light exposures caused a very intense vascular PDT reaction. Moderate doses of injected ALA concentration (similar to 0.06%), selectively targeted EG. Low doses (<= 0.016%) targeted fat; producing fat necrosis with minimal inflammation, manifested both clinically and histologically. In contrast to topical ALA-PDT, intradermal ALA-PDT can effectively photosensitize deep skin structures. Conclusion: Potentially, intradermal ALA-PDT using various ALA concentrations may be useful for treating vascular lesions (malformations, hemangiomas, tumors), EG/AG disorders, fat or deep targets in skin. Lasers Surg. Med. 43: 621-631, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Sakamoto, Fernanda H.; Doukas, Apostolos G.; Farinelli, William A.; Tannous, Zeina; Su, Yao; Smith, Nicholas A.; Anderson, R. Rox] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. [Sakamoto, Fernanda H.] Univ Fed Sao Paulo, Dept Dermatol, Escola Paulista Med UNIFESP EPM, Sao Paulo, Brazil. [Smith, Nicholas A.] Harvard Univ, Cambridge, MA 02138 USA. [Zurakowski, David] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Surg, Boston, MA 02115 USA. RP Anderson, RR (reprint author), 55 Fruit St,BHX 630, Boston, MA 02114 USA. EM rranderson@partners.org NR 36 TC 8 Z9 9 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD SEP PY 2011 VL 43 IS 7 BP 621 EP 631 DI 10.1002/lsm.21073 PG 11 WC Dermatology; Surgery SC Dermatology; Surgery GA 811PA UT WOS:000294223300012 PM 22057490 ER PT J AU Kharkwal, GB Sharma, SK Huang, YY Dai, TH Hamblin, MR AF Kharkwal, Gitika B. Sharma, Sulbha K. Huang, Ying-Ying Dai, Tianhong Hamblin, Michael R. TI Photodynamic Therapy for Infections: Clinical Applications SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE photodynamic therapy; infectious disease; amimolevulinic acid; phenothiazinium dye; bacteria; fungus; virus; parasite ID TOPICAL 5-AMINOLEVULINIC ACID; GRAM-NEGATIVE BACTERIA; SELECTIVE ANTIMICROBIAL PHOTOSENSITIZERS; ACNE-VULGARIS; HELICOBACTER-PYLORI; CUTANEOUS LEISHMANIASIS; METHYL-AMINOLEVULINATE; NONSURGICAL TREATMENT; TRICHOPHYTON-RUBRUM; CONDYLOMATA ACUMINATA AB Background and Objective: Photodynamic therapy (PDT) was discovered over 100 years ago by its ability to kill various microorganisms when the appropriate dye and light were combined in the presence of oxygen. However it is only in relatively recent times that PDT has been studied as a treatment for various types of localized infections. This resurgence of interest has been partly motivated by the alarming increase in drug resistance amongst bacteria and other pathogens. This review will focus on the clinical applications of antimicrobial PDT. Study Design/Materials and Methods: The published peer-reviewed literature was reviewed between 1960 and 2011. Results: The basics of antimicrobial PDT are discussed. Clinical applications of antimicrobial PDT to localized viral infections caused by herpes and papilloma viruses, and nonviral dermatological infections such as acne and other yeast, fungal and bacterial skin infections are covered. PDT has been used to treat bacterial infections in brain abscesses and non-healing ulcers. PDT for dental infections including periodontitis and endodontics has been well studied. PDT has also been used for cutaneous Leishmaniasis. Clinical trials of PDT and blue light alone therapy for gastric Helicobacter pylori infection are also covered. Conclusion: As yet clinical PDT for infections has been mainly in the field of dermatology using 5-aminolevulanic acid and in dentistry using phenothiazinium dyes. We expect more to see applications of PDT to more challenging infections using advanced antimicrobial photosensitizers targeted to microbial cells in the years to come. Lasers Surg. Med. 43: 755-767, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Kharkwal, Gitika B.; Sharma, Sulbha K.; Huang, Ying-Ying; Dai, Tianhong; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kharkwal, Gitika B.; Huang, Ying-Ying; Dai, Tianhong; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), BAR314B,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01A1050875]; Airlift Research Foundation [109421] FX Contract grant sponsor: US NIH; Contract grant number: R01A1050875; Contract grant sponsor: Airlift Research Foundation; Contract grant number: 109421. NR 115 TC 112 Z9 120 U1 2 U2 41 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD SEP PY 2011 VL 43 IS 7 BP 755 EP 767 DI 10.1002/lsm.21080 PG 13 WC Dermatology; Surgery SC Dermatology; Surgery GA 811PA UT WOS:000294223300025 PM 22057503 ER PT J AU Wang, CY Mayer, JA Mazumdar, A Fertuck, K Kim, H Brown, M Brown, PH AF Wang, Chunyu Mayer, Julie Ann Mazumdar, Abhijit Fertuck, Kirsten Kim, Heetae Brown, Myles Brown, Powel H. TI Estrogen Induces c-myc Gene Expression via an Upstream Enhancer Activated by the Estrogen Receptor and the AP-1 Transcription Factor SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER-CELLS; FACTOR CROSS-TALK; ONCOGENE EXPRESSION; BINDING-SITES; TARGET GENE; KAPPA-B; GROWTH; ALPHA; JUN; MECHANISM AB c-myc oncogene is implicated in tumorigenesis of many cancers, including breast cancer. Although c-myc is a well-known estrogen-induced gene, its promoter has no estrogen-response element, and the underlying mechanism by which estrogen induces its expression remains obscure. Recent genome-wide studies by us and others suggested that distant elements may mediate estrogen induction of gene expression. In this study, we investigated the molecular mechanism by which estrogen induces c-myc expression with a focus on these distal elements. Estrogen rapidly induced c-myc expression in estrogen receptor (ER)-positive breast cancer cells. Although estrogen had little effect on c-myc proximal promoter activity, it did stimulate the activity of a luciferase reporter containing a distal 67-kb enhancer. Estrogen induction of this luciferase reporter was dependent upon both a half-estrogen response element and an activator protein 1 (AP-1) site within this enhancer, which are conserved across 11 different mammalian species. Small interfering RNA experiments and chromatin immunoprecipitation assays demonstrated the necessity of ER and AP-1 cross talk for estrogen to induce c-myc expression. TAM67, the AP-1 dominant negative, partially inhibited estrogen induction of c-myc expression and suppressed estrogen-induced cell cycle progression. Together, these results demonstrate a novel pathway of estrogen regulation of gene expression by cooperation between ER and AP-1 at the distal enhancer element and that AP-1 is involved in estrogen induction of the c-myc oncogene. These results solve the long-standing question in the field of endocrinology of how estrogen induces c-myc expression. (Molecular Endocrinology 25: 1527-1538, 2011) C1 [Wang, Chunyu; Mayer, Julie Ann; Mazumdar, Abhijit; Brown, Powel H.] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. [Fertuck, Kirsten; Brown, Myles] Dana Farber Canc Inst, Div Mol & Cellular Oncol, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fertuck, Kirsten] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Kim, Heetae] Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. RP Brown, PH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. EM phbrown@mdanderson.org OI Brown, Myles/0000-0002-8213-1658 FU National Institutes of Health [R01-CA123246, R01-DK074967] FX This work was supported by National Institutes of Health grants R01-CA123246 and R01-DK074967. NR 48 TC 52 Z9 53 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 2011 VL 25 IS 9 BP 1527 EP 1538 DI 10.1210/me.2011-1037 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 813CN UT WOS:000294344500004 PM 21835891 ER PT J AU Villeda, SA Luo, J Mosher, KI Zou, BD Britschgi, M Bieri, G Stan, TM Fainberg, N Ding, ZQ Eggel, A Lucin, KM Czirr, E Park, JS Couillard-Despres, S Aigner, L Li, G Peskind, ER Kaye, JA Quinn, JF Galasko, DR Xie, XMS Rando, TA Wyss-Coray, T AF Villeda, Saul A. Luo, Jian Mosher, Kira I. Zou, Bende Britschgi, Markus Bieri, Gregor Stan, Trisha M. Fainberg, Nina Ding, Zhaoqing Eggel, Alexander Lucin, Kurt M. Czirr, Eva Park, Jeong-Soo Couillard-Despres, Sebastien Aigner, Ludwig Li, Ge Peskind, Elaine R. Kaye, Jeffrey A. Quinn, Joseph F. Galasko, Douglas R. Xie, Xinmin S. Rando, Thomas A. Wyss-Coray, Tony TI The ageing systemic milieu negatively regulates neurogenesis and cognitive function SO NATURE LA English DT Article ID ADULT HIPPOCAMPAL NEUROGENESIS; NEURAL STEM-CELLS; LONG-TERM POTENTIATION; PROGENITOR CELLS; SELF-RENEWAL; AGED MICE; MEMORY; BRAIN; NEURONS; MODEL AB In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions(1). Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise(1). Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines-including CCL11 (also known as eotaxin)-the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors. C1 [Villeda, Saul A.; Luo, Jian; Mosher, Kira I.; Britschgi, Markus; Bieri, Gregor; Stan, Trisha M.; Fainberg, Nina; Ding, Zhaoqing; Eggel, Alexander; Lucin, Kurt M.; Czirr, Eva; Park, Jeong-Soo; Rando, Thomas A.; Wyss-Coray, Tony] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. [Villeda, Saul A.; Mosher, Kira I.; Wyss-Coray, Tony] Stanford Univ, Sch Med, Neurosci IDP Program, Stanford, CA 94305 USA. [Zou, Bende; Xie, Xinmin S.] AfaSci Res Lab, Redwood City, CA 94063 USA. [Bieri, Gregor] Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, Sch Life Sci, CH-1015 Lausanne, Switzerland. [Stan, Trisha M.; Ding, Zhaoqing; Wyss-Coray, Tony] Stanford Univ, Sch Med, Immunol IDP Program, Stanford, CA 94305 USA. [Couillard-Despres, Sebastien; Aigner, Ludwig] Paracelsus Med Univ, Inst Mol Regenerat Med, A-5020 Salzburg, Austria. [Li, Ge; Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. [Peskind, Elaine R.] Vet Affairs NW Network Mental Illness Res Educ &, Seattle, WA 98108 USA. [Kaye, Jeffrey A.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97201 USA. [Kaye, Jeffrey A.; Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR 97207 USA. [Galasko, Douglas R.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Rando, Thomas A.; Wyss-Coray, Tony] VA Palo Alto Hlth Care Syst, Ctr Tissue Regenerat Repair & Restorat, Palo Alto, CA 94304 USA. [Rando, Thomas A.] Stanford Univ, Sch Med, Glenn Labs Biol Aging, Stanford, CA 94305 USA. RP Wyss-Coray, T (reprint author), Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Stanford, CA 94305 USA. EM twc@stanford.edu RI Luo, Jian/B-8449-2014; OI Luo, Jian/0000-0002-2064-8467; Kaye, Jeffrey/0000-0002-9971-3478; Eggel, Alexander/0000-0001-8746-3339 FU Department of Veterans Affairs; National Institutes of Health Institute on Aging [R01 AG027505, P30AG08017]; California Initiative for Regenerative Medicine; National Institutes of Health [R01 MH078194]; Larry L. Hillblom Foundation [2008-A-023-FEL]; Feodor-Lynen postdoctoral fellowship; Swiss National Science Foundation; National Science Foundation; Kirschstein NRSA [AG034045-01, 1 F31 NS066676-01A1] FX We thank A. Brunet for critically reading the manuscript; M. Buckwalter for parabiosis instruction; T.-T. Huang for irradiation instruction; R. Corniola and C. Clelland for behavioural advice, S. Bauer Huang, H. Johns, J. Sun, H. Hefner, H. Alabsi and I. Villeda for technical assistance. This work was supported by grants from Anonymous (T.W.-C.), Department of Veterans Affairs (T.W.-C.), National Institutes of Health Institute on Aging (R01 AG027505, T.W.-C.), a California Initiative for Regenerative Medicine Award (T.W.-C.), National Institutes of Health (R01 MH078194, X.S.X.), National Institutes of Health Institute on Aging (P30AG08017, J.A.K.), a National Institutes of Health Director's Pioneer Award (T.A.R.), a Larry L. Hillblom Foundation postdoctoral fellowship (K.M.L.; 2008-A-023-FEL), a Feodor-Lynen postdoctoral fellowship (E.C.), a Swiss National Science Foundation postdoctoral fellowship (A.E.), a National Science Foundation predoctoral fellowship (S.A.V.; K.I.M.; T.M.S.), and Kirschstein NRSA predoctoral fellowships (1 F31 AG034045-01, S.A.V.; 1 F31 NS066676-01A1, Z.D.). NR 32 TC 453 Z9 466 U1 17 U2 127 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 1 PY 2011 VL 477 IS 7362 BP 90 EP U157 DI 10.1038/nature10357 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 813XT UT WOS:000294404300037 PM 21886162 ER PT J AU Boulant, S Kural, C Zeeh, JC Ubelmann, F Kirchhausen, T AF Boulant, Steeve Kural, Comert Zeeh, Jean-Christophe Ubelmann, Florent Kirchhausen, Tomas TI Actin dynamics counteract membrane tension during clathrin-mediated endocytosis SO NATURE CELL BIOLOGY LA English DT Article ID HUNTINGTIN-INTERACTING PROTEIN-1; POLARIZED EPITHELIAL-CELLS; CANINE KIDNEY-CELLS; COATED PITS; APICAL SURFACE; N-WASP; HIP1-RELATED PROTEIN; PLASMA-MEMBRANE; ARP2/3 COMPLEX; CYTOCHALASIN-D AB Clathrin-mediated endocytosis is independent of actin dynamics in many circumstances but requires actin polymerization in others. We show that membrane tension determines the actin dependence of clathrin-coat assembly. As found previously, clathrin assembly supports formation of mature coated pits in the absence of actin polymerization on both dorsal and ventral surfaces of non-polarized mammalian cells, and also on basolateral surfaces of polarized cells. Actin engagement is necessary, however, to complete membrane deformation into a coated pit on apical surfaces of polarized cells and, more generally, on the surface of any cell in which the plasma membrane is under tension from osmotic swelling or mechanical stretching. We use these observations to alter actin dependence experimentally and show that resistance of the membrane to propagation of the clathrin lattice determines the distinction between 'actin dependent and 'actin independent'. We also find that light-chain-bound Hip1R mediates actin engagement. These data thus provide a unifying explanation for the role of actin dynamics in coated-pit budding. C1 [Boulant, Steeve; Kural, Comert; Zeeh, Jean-Christophe; Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Boulant, Steeve; Kural, Comert; Zeeh, Jean-Christophe; Kirchhausen, Tomas] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Boulant, Steeve; Kural, Comert; Zeeh, Jean-Christophe; Kirchhausen, Tomas] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Ubelmann, Florent] Inst Curie Paris, Lab Morphogenese & Signalisat Cellulaires, Paris 05, France. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu OI Ubelmann, Florent/0000-0002-3746-8614 FU NIH [GM 075252]; Harvard Digestive Disease Consortium; NIH, New England Regional Center of Excellence in Biodefense and Emerging Infectious Diseases [U54 AI057159] FX This work was supported by NIH grant National Institutes of Health GM 075252 (T.K.) and a Harvard Digestive Disease Consortium Feasibility Award (S.B.). We express gratitude to E. Marino (supported by NIH grant U54 AI057159, New England Regional Center of Excellence in Biodefense and Emerging Infectious Diseases) for maintaining the imaging resource used in this study and to S.C. Harrison for help with describing the force contributed by membrane tension and for editorial assistance. We gratefully acknowledge M. Ericsson and I. Kim for preparation of samples for electron microscopic analysis and members of the Kirchhausen laboratory for thought-provoking discussions. We thank M. Arpin (Centre National de la Recherche Scientifique (CNRS)/Morphogenese et Signalisation cellulaires, Paris, France) and C. Revenu (Centre National de la Recherche Scientifique/Institut Curie, Paris, France) for the antibody specific for villin-1. We also acknowledge S. Robine for important suggestions involving the villin-l/villin-2 depletion experiments. NR 45 TC 159 Z9 159 U1 4 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2011 VL 13 IS 9 BP 1124 EP U158 DI 10.1038/ncb2307 PG 10 WC Cell Biology SC Cell Biology GA 814WD UT WOS:000294487000018 PM 21841790 ER PT J AU Chen, T Ozel, D Qiao, Y Harbinski, F Chen, LM Denoyelle, S He, XY Zvereva, N Supko, JG Chorev, M Halperin, JA Aktas, BH AF Chen, Ting Ozel, Duygu Qiao, Yuan Harbinski, Fred Chen, Limo Denoyelle, Severine He, Xiaoying Zvereva, Nela Supko, Jeffrey G. Chorev, Michael Halperin, Jose A. Aktas, Bertal H. TI Chemical genetics identify eIF2 alpha kinase heme-regulated inhibitor as an anticancer target SO NATURE CHEMICAL BIOLOGY LA English DT Article ID UNFOLDED-PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; TRANSLATION INITIATION; DIABETES-MELLITUS; MAMMALIAN-CELLS; ER STRESS; IN-VIVO; EXPRESSION; PERK; PHOSPHORYLATION AB Translation initiation plays a critical role in cellular homeostasis, proliferation, differentiation and malignant transformation. Consistently, increasing the abundance of the eIF2-GTP-tRNA(i)(Met) translation initiation complex transforms normal cells and contributes to cancer initiation and the severity of some anemias. The chemical modifiers of the eIF2-GTP-tRNA(i)(Met) ternary complex are therefore invaluable tools for studying its role in the pathobiology of human disorders and for determining whether this complex can be pharmacologically targeted for therapeutic purposes. Using a cell-based assay, we identified N,N'-diarylureas as unique inhibitors of ternary complex accumulation. Direct functional-genetic and biochemical evidence demonstrated that the N,N'-diarylureas activate heme-regulated inhibitor kinase, thereby phosphorylating eIF2 alpha and reducing the abundance of the ternary complex. Using tumor cell proliferation in vitro and tumor growth in vivo as paradigms, we demonstrate that N,N'-diarylureas are potent and specific tools for studying the role of eIF2-GTP-tRNA(i)(Met) ternary complex in the pathobiology of human disorders. C1 [Chen, Ting; Ozel, Duygu; Qiao, Yuan; Harbinski, Fred; Chen, Limo; Denoyelle, Severine; Chorev, Michael; Halperin, Jose A.; Aktas, Bertal H.] Harvard Univ, Sch Med, Lab Translat Res, Boston, MA 02115 USA. [He, Xiaoying; Zvereva, Nela; Supko, Jeffrey G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chorev, Michael; Halperin, Jose A.; Aktas, Bertal H.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Chen, T (reprint author), Harvard Univ, Sch Med, Lab Translat Res, Boston, MA 02115 USA. EM huseyin_aktas@hms.harvard.edu RI Chen, Ting/A-2124-2012 FU NIH [NCDDG 5 U19 CA87427]; Susan B. Komen Foundation for Cancer Research [BCTR0707713]; US Department of Defense [W81ZWH-05-1-0096]; US National Institutes of Health [R21AG032546] FX We thank D.C. Tosteson (Harvard Medical School), mentor and role model to authors, for encouragement; J.J. Chen for providing the HRI expression plasmid; and M. Tosteson for critical comments on the manuscript. This work was supported in part by NIH grant NCDDG 5 U19 CA87427 to J.A.H., Susan B. Komen Foundation for Cancer Research grant BCTR0707713, US Department of Defense grant no. W81ZWH-05-1-0096 and US National Institutes of Health grant no. R21AG032546 to B.H.A. NR 42 TC 35 Z9 35 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD SEP PY 2011 VL 7 IS 9 BP 610 EP 616 DI 10.1038/NCHEMBIO.613 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 813QG UT WOS:000294381400011 PM 21765405 ER PT J AU Li, M Zhao, H Zhang, XS Wood, LD Anders, RA Choti, MA Pawlik, TM Daniel, HD Kannangai, R Offerhaus, GJA Velculescu, VE Wang, LF Zhou, SB Vogelstein, B Hruban, RH Papadopoulos, N Cai, JQ Torbenson, MS Kinzler, KW AF Li, Meng Zhao, Hong Zhang, Xiaosong Wood, Laura D. Anders, Robert A. Choti, Michael A. Pawlik, Timothy M. Daniel, Hubert D. Kannangai, Rajesh Offerhaus, G. Johan A. Velculescu, Victor E. Wang, Linfang Zhou, Shibin Vogelstein, Bert Hruban, Ralph H. Papadopoulos, Nick Cai, Jianqiang Torbenson, Michael S. Kinzler, Kenneth W. TI Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma SO NATURE GENETICS LA English DT Article ID HEPATITIS-B-VIRUS; EXPRESSION; HEPATOCARCINOGENESIS; AFLATOXIN AB Through exomic sequencing of ten hepatitis C virus (HCV)-associated hepatocellular carcinomas (HCC) and subsequent evaluation of additional affected individuals, we discovered novel inactivating mutations of ARID2 in four major subtypes of HCC (HCV-associated HCC, hepatitis B virus (HBV)-associated HCC, alcohol-associated HCC and HCC with no known etiology). Notably, 18.2% of individuals with HCV-associated HCC in the United States and Europe harbored ARID2 inactivation mutations, suggesting that ARID2 is a tumor suppressor gene that is relatively commonly mutated in this tumor subtype. C1 [Li, Meng; Velculescu, Victor E.; Zhou, Shibin; Vogelstein, Bert; Papadopoulos, Nick; Kinzler, Kenneth W.] Johns Hopkins Univ, Sch Med, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21218 USA. [Zhao, Hong; Cai, Jianqiang] Chinese Acad Med Sci, Dept Abdominal Surg Oncol, Canc Hosp, Beijing 100730, Peoples R China. [Zhao, Hong; Wang, Linfang; Cai, Jianqiang] Peking Union Med Coll, Beijing 100021, Peoples R China. [Zhang, Xiaosong] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wood, Laura D.; Anders, Robert A.; Daniel, Hubert D.; Kannangai, Rajesh; Hruban, Ralph H.; Torbenson, Michael S.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Choti, Michael A.; Pawlik, Timothy M.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Offerhaus, G. Johan A.] Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands. [Wang, Linfang] Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100730, Peoples R China. RP Kinzler, KW (reprint author), Johns Hopkins Univ, Sch Med, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21218 USA. EM caijianqiang188@sina.com; mtorben@jhmi.edu; kinzlke@jhmi.edu RI Daniel, Hubert Darius/B-7430-2011; Papadopoulos, Nickolas/K-7272-2012 FU Virginia and D.K. Ludwig Fund for Cancer Research; US National Institutes of Health [CA43460, CA57345, CA62924, CA121113, DK078686, DK080736, DK081417]; AACR; National Science and Technology Major Project [2008ZX10002-025] FX We thank N. Silliman, J. Ptak, L. Dobbyn, J. Schaeffer, M. Whalen, Z. Khan, J. Ma, Z. Wang and R. Mi for expert technical assistance. This work was supported by The Virginia and D.K. Ludwig Fund for Cancer Research and US National Institutes of Health grants CA43460, CA57345, CA62924, CA121113, DK078686, DK080736, DK081417, AACR Stand Up to Cancer Dream Team Translational Cancer Research Grant and National Science and Technology Major Project Grant 2008ZX10002-025. NR 14 TC 194 Z9 205 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2011 VL 43 IS 9 BP 828 EP 829 DI 10.1038/ng.903 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 812XE UT WOS:000294325800006 PM 21822264 ER PT J AU Locasale, JW Grassian, AR Melman, T Lyssiotis, CA Mattaini, KR Bass, AJ Heffron, G Metallo, CM Muranen, T Sharfi, H Sasaki, AT Anastasiou, D Mullarky, E Vokes, NI Sasaki, M Beroukhim, R Stephanopoulos, G Ligon, AH Meyerson, M Richardson, AL Chin, L Wagner, G Asara, JM Brugge, JS Cantley, LC Vander Heiden, MG AF Locasale, Jason W. Grassian, Alexandra R. Melman, Tamar Lyssiotis, Costas A. Mattaini, Katherine R. Bass, Adam J. Heffron, Gregory Metallo, Christian M. Muranen, Taru Sharfi, Hadar Sasaki, Atsuo T. Anastasiou, Dimitrios Mullarky, Edouard Vokes, Natalie I. Sasaki, Mika Beroukhim, Rameen Stephanopoulos, Gregory Ligon, Azra H. Meyerson, Matthew Richardson, Andrea L. Chin, Lynda Wagner, Gerhard Asara, John M. Brugge, Joan S. Cantley, Lewis C. Vander Heiden, Matthew G. TI Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis SO NATURE GENETICS LA English DT Article ID MASS ISOTOPOMER DISTRIBUTIONS; HUMAN-BREAST-CANCER; 3-PHOSPHOGLYCERATE DEHYDROGENASE; METABOLISM; SERINE; PROLIFERATION; BIOSYNTHESIS; EXPRESSION; ABUNDANCE; GLYCINE AB Most tumors exhibit increased glucose metabolism to lactate, however, the extent to which glucose-derived metabolic fluxes are used for alternative processes is poorly understood(1,2). Using a metabolomics approach with isotope labeling, we found that in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through phosphoglycerate dehydrogenase (PHGDH). An analysis of human cancers showed that PHGDH is recurrently amplified in a genomic region of focal copy number gain most commonly found in melanoma. Decreasing PHGDH expression impaired proliferation in amplified cell lines. Increased expression was also associated with breast cancer subtypes, and ectopic expression of PHGDH in mammary epithelial cells disrupted acinar morphogenesis and induced other phenotypic alterations that may predispose cells to transformation. Our findings show that the diversion of glycolytic flux into a specific alternate pathway can be selected during tumor development and may contribute to the pathogenesis of human cancer. C1 [Locasale, Jason W.; Melman, Tamar; Lyssiotis, Costas A.; Sharfi, Hadar; Sasaki, Atsuo T.; Anastasiou, Dimitrios; Mullarky, Edouard; Sasaki, Mika; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Locasale, Jason W.; Melman, Tamar; Lyssiotis, Costas A.; Sharfi, Hadar; Sasaki, Atsuo T.; Anastasiou, Dimitrios; Mullarky, Edouard; Sasaki, Mika; Asara, John M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. [Grassian, Alexandra R.; Muranen, Taru; Brugge, Joan S.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Mattaini, Katherine R.; Vokes, Natalie I.; Vander Heiden, Matthew G.] MIT, Dept Biol, Koch Inst Integrat Canc Res, Cambridge, MA USA. [Bass, Adam J.; Beroukhim, Rameen; Ligon, Azra H.; Meyerson, Matthew; Richardson, Andrea L.; Chin, Lynda; Vander Heiden, Matthew G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bass, Adam J.; Beroukhim, Rameen; Meyerson, Matthew] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA USA. [Heffron, Gregory; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biochem & Mol Pharmacol, Boston, MA USA. [Metallo, Christian M.; Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Beroukhim, Rameen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ligon, Azra H.; Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Locasale, JW (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM jlocasal@bidmc.harvard.edu; lcantley@hms.harvard.edu; mvh@mit.edu RI Meyerson, Matthew/E-7123-2012; Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Locasale, Jason/0000-0002-7766-3502 FU US National Institutes of Health (NIH); American Cancer Society; National Science Foundation (NSF); NIH; National Cancer Institute (NCI); Damon Runyon Cancer Research Foundation; Burroughs Wellcome Fund FX Microscopy data for this study were acquired and analyzed in the Nikon Imaging Center at Harvard Medical School. J.W.L. was supported by postdoctoral fellowships from the US National Institutes of Health (NIH) and the American Cancer Society. A. R. G. is a recipient of a National Science Foundation (NSF) Graduate Research Fellowship. L. C. C. and J.S.B. were supported by grants from the NIH and the National Cancer Institute (NCI). M. G. V. H. was supported by grants from the NIH, NCI, Smith Family, Damon Runyon Cancer Research Foundation and the Burroughs Wellcome Fund. We thank N. Vena for technical assistance with the FISH analysis and K. Webster and I. Carrecedo for help with immunohistochemistry. We thank J. Rabinowitz, A. Carrecedo and S.-C. Ng for helpful comments on the manuscript. NR 31 TC 324 Z9 329 U1 12 U2 69 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2011 VL 43 IS 9 BP 869 EP U79 DI 10.1038/ng.890 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 812XE UT WOS:000294325800013 PM 21804546 ER PT J AU Lyons, TR O'Brien, J Borges, VF Conklin, MW Keely, PJ Eliceiri, KW Marusyk, A Tan, AC Schedin, P AF Lyons, Traci R. O'Brien, Jenean Borges, Virginia F. Conklin, Matthew W. Keely, Patricia J. Eliceiri, Kevin W. Marusyk, Andriy Tan, Aik-Choon Schedin, Pepper TI Postpartum mammary gland involution drives progression of ductal carcinoma in situ through collagen and COX-2 SO NATURE MEDICINE LA English DT Article ID BREAST-CANCER METASTASIS; GENE-EXPRESSION SIGNATURE; CYCLOOXYGENASE-2 EXPRESSION; REPRODUCTIVE STATE; COLORECTAL-CANCER; CELL-MIGRATION; SURVIVAL; PREGNANCY; RISK; INFLAMMATION AB The prognosis of breast cancer in young women is influenced by reproductive history. Women diagnosed within 5 years postpartum have worse prognosis than nulliparous women or women diagnosed during pregnancy. Here we describe a mouse model of postpartum breast cancer that identifies mammary gland involution as a driving force of tumor progression. In this model, human breast cancer cells exposed to the involuting mammary microenvironment form large tumors that are characterized by abundant fibrillar collagen, high cyclooxygenase-2 (COX-2) expression and an invasive phenotype. In culture, tumor cells are invasive in a fibrillar collagen and COX-2-dependent manner. In the involuting mammary gland, inhibition of COX-2 reduces the collagen fibrillogenesis associated with involution, as well as tumor growth and tumor cell infiltration to the lung. These data support further research to determine whether women at high risk for postpartum breast cancer would benefit from treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) during postpartum involution. C1 [Lyons, Traci R.; O'Brien, Jenean; Borges, Virginia F.; Tan, Aik-Choon; Schedin, Pepper] Univ Colorado, Dept Med, Div Med Oncol, Aurora, CO USA. [O'Brien, Jenean; Schedin, Pepper] Univ Colorado, Program Canc Biol, Aurora, CO USA. [Borges, Virginia F.; Tan, Aik-Choon; Schedin, Pepper] Univ Colorado, Ctr Canc, Aurora, CO USA. [Conklin, Matthew W.; Keely, Patricia J.] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI USA. [Conklin, Matthew W.; Keely, Patricia J.] Univ Wisconsin, UW Carbone Canc Ctr, Madison, WI USA. [Conklin, Matthew W.; Keely, Patricia J.; Eliceiri, Kevin W.] Univ Wisconsin, Lab Cell & Mol Biol, Lab Opt & Computat Instrumentat, Madison, WI USA. [Marusyk, Andriy] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA. [Schedin, Pepper] AMC Canc Res Ctr, Denver, CO USA. RP Schedin, P (reprint author), Univ Colorado, Dept Med, Div Med Oncol, Anschutz Med Campus, Aurora, CO USA. EM pepper.schedin@ucdenver.edu RI Tan, Aik Choon/A-3135-2011; OI Eliceiri, Kevin/0000-0001-8678-670X; Tan, Aik Choon/0000-0003-2955-8369 FU Department of Defense [BC060531, BC074970, BC087579, BC073482]; Komen Foundation [KG090629]; Mary Kay Ash Foundation [078-08]; AMC; University of Colorado Cancer Center; American Cancer Society New England Division [PF-08-257-01-CSM] FX We are grateful to K. Polyak (Harvard Medical School) and M. Hu for providing MCF10DCIS parental cells and advice, C. Ambrosone, L. Hines, A. Thor and S. Edgerton for human tissue acquisition, M. Garcia and M. Skokan for FISH analysis, M. Lucia and R. Wilson for assistance with quantitative immunohistochemistry analysis, O. Maller, K. Bell, S. Jindal, K. Hedman, D. Powell, N. DeWaele and Y. Kwarteng for technical assistance, and S. Sillau for advanced statistical analyses. We thank K. Polyak, A. Thorburn, M. Moss and Nature Medicine reviewers for critical evaluation of the manuscript, and we gratefully acknowledge the subjects for their contribution to this research. This work was supported by Department of Defense Synergistic Idea Award BC060531, Komen Foundation grant KG090629, Mary Kay Ash Foundation grant 078-08, AMC cancer fund, and University of Colorado Cancer Center grants to P.S. and V.B., Department of Defense Award BC074970 to P.J.K., American Cancer Society New England Division Postdoctoral Fellowship Spin Odyssey PF-08-257-01-CSM to T.R.L., Department of Defense Postdoctoral grant BC087579 to A.M., and Department of Defense Predoctoral grant BC073482 to J.O. NR 58 TC 132 Z9 133 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2011 VL 17 IS 9 BP 1109 EP U116 DI 10.1038/nm.2416 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 816MM UT WOS:000294605100031 PM 21822285 ER PT J AU Liu, PX Cheng, HL Santiago, S Raeder, M Zhang, F Isabella, A Yang, J Semaan, DJ Chen, CZ Fox, EA Gray, NS Monahan, J Schlegel, R Beroukhim, R Mills, GB Zhao, JJ AF Liu, Pixu Cheng, Hailing Santiago, Stephanie Raeder, Maria Zhang, Fan Isabella, Adam Yang, Janet Semaan, Derek J. Chen, Changzhong Fox, Edward A. Gray, Nathanael S. Monahan, John Schlegel, Robert Beroukhim, Rameen Mills, Gordon B. Zhao, Jean J. TI Oncogenic PIK3CA-driven mammary tumors frequently recur via PI3K pathway-dependent and PI3K pathway-independent mechanisms SO NATURE MEDICINE LA English DT Article ID BREAST-CANCER; PHOSPHATIDYLINOSITOL 3-KINASE; MET AMPLIFICATION; EPITHELIAL-CELLS; COPY NUMBER; MUTATIONS; PIK3CA; INHIBITORS; GDC-0941; PTEN AB PIK3CA gain-of-function mutations are a common oncogenic event in human malignancy(1-4), making phosphatidylinositol 3-kinase (PI3K) a target for cancer therapy. Despite the promise of targeted therapy, resistance often develops, leading to treatment failure. To elucidate mechanisms of resistance to PI3K-targeted therapy, we constructed a mouse model of breast cancer conditionally expressing human PIK3CA(H1047R). Notably, most PIK3CA(H1047R)-driven mammary tumors recurred after PIK3CA(H1047R) inactivation. Genomic analyses of recurrent tumors revealed multiple lesions, including focal amplification of Met or Myc (also known as c-Met and c-Myc, respectively). Whereas Met amplification led to tumor survival dependent on activation of endogenous PI3K, tumors with Myc amplification became independent of the PI3K pathway. Functional analyses showed that Myc contributed to oncogene independence and resistance to PI3K inhibition. Notably, PIK3CA mutations and c-MYC elevation co-occur in a substantial fraction of human breast tumors. Together, these data suggest that c-MYC elevation represents a potential mechanism by which tumors develop resistance to current PI3K-targeted therapies. C1 [Liu, Pixu; Cheng, Hailing; Santiago, Stephanie; Raeder, Maria; Isabella, Adam; Yang, Janet; Semaan, Derek J.; Gray, Nathanael S.; Beroukhim, Rameen; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Liu, Pixu; Cheng, Hailing; Santiago, Stephanie; Gray, Nathanael S.; Zhao, Jean J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Cheng, Hailing; Zhao, Jean J.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Raeder, Maria] Univ Bergen, Dept Clin Med, Bergen, Norway. [Raeder, Maria] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway. [Zhang, Fan; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Fox, Edward A.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fox, Edward A.; Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Monahan, John; Schlegel, Robert] Novartis Inst Biomed Res, Cambridge, MA USA. [Beroukhim, Rameen] Broad Inst, Cambridge, MA USA. RP Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM jean_zhao@dfci.harvard.edu OI Monahan, John/0000-0002-3125-8704 FU US National Institutes of Health [CA134502, CA148164-01, K08CA122833]; Stand Up To Cancer; Dana Farber Harvard Cancer Center breast cancer SPORE [P50 CA089393-08S1]; US Department of Defense [BC051565]; V Foundation; Claudia Barr Program FX We thank T. Roberts, L. Cantley and W. Sellers for scientific discussions and suggestions. We thank L. Clayton and D. Silver for critical review of this manuscript. We thank R. Bronson for pathological analyses of tumor samples. We thank C. Li and E. Allgood for technical assistance. We thank L. Chodosh (University of Pennsylvania School of Medicine) for providing MMTV-rtTA mice. This work was supported by US National Institutes of Health grants CA134502 (J.J.Z.), CA148164-01 (J.J.Z. and N.S.G.) and K08CA122833 (R.B.), Stand Up To Cancer (J.J.Z. and G.B.M.), Dana Farber Harvard Cancer Center breast cancer SPORE grant P50 CA089393-08S1 (J.J.Z.), the US Department of Defense (BC051565 to J.J.Z.), the V Foundation (J.J.Z. and R.B.) and the Claudia Barr Program (J.J.Z.). In compliance with Harvard Medical School guidelines, we disclose that J.J.Z. and R.B. are consultants for Novartis Pharmaceuticals. NR 28 TC 110 Z9 111 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2011 VL 17 IS 9 BP 1116 EP U122 DI 10.1038/nm.2402 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 816MM UT WOS:000294605100032 PM 21822287 ER PT J AU Panizzi, P Nahrendorf, M Figueiredo, JL Panizzi, J Marinelli, B Iwamoto, Y Keliher, E Maddur, AA Waterman, P Kroh, HK Leuschner, F Aikawa, E Swirski, FK Pittet, MJ Hackeng, TM Fuentes-Prior, P Schneewind, O Bock, PE Weissleder, R AF Panizzi, Peter Nahrendorf, Matthias Figueiredo, Jose-Luiz Panizzi, Jennifer Marinelli, Brett Iwamoto, Yoshiko Keliher, Edmund Maddur, Ashoka A. Waterman, Peter Kroh, Heather K. Leuschner, Florian Aikawa, Elena Swirski, Filip K. Pittet, Mikael J. Hackeng, Tilman M. Fuentes-Prior, Pablo Schneewind, Olaf Bock, Paul E. Weissleder, Ralph TI In vivo detection of Staphylococcus aureus endocarditis by targeting pathogen-specific prothrombin activation SO NATURE MEDICINE LA English DT Article ID COAGULASE-DEFICIENT MUTANTS; INFECTIVE ENDOCARDITIS; STAPHYLOCOAGULASE; DIAGNOSIS; VIRULENCE; PROBES AB Coagulase-positive Staphylococcus aureus (S. aureus) is the major causal pathogen of acute endocarditis, a rapidly progressing, destructive infection of the heart valves. Bacterial colonization occurs at sites of endothelial damage, where, together with fibrin and platelets, the bacteria initiate the formation of abnormal growths known as vegetations. Here we report that an engineered analog of prothrombin could be used to detect S. aureus in endocarditic vegetations via noninvasive fluorescence or positron emission tomography (PET) imaging. These prothrombin derivatives bound staphylocoagulase and intercalated into growing bacterial vegetations. We also present evidence for bacterial quorum sensing in the regulation of staphylocoagulase expression by S. aureus. Staphylocoagulase expression was limited to the growing edge of mature vegetations, where it was exposed to the host and co-localized with the imaging probe. When endocarditis was induced with an S. aureus strain with genetic deletion of coagulases, survival of mice improved, highlighting the role of staphylocoagulase as a virulence factor. C1 [Panizzi, Peter; Nahrendorf, Matthias; Figueiredo, Jose-Luiz; Marinelli, Brett; Iwamoto, Yoshiko; Keliher, Edmund; Waterman, Peter; Leuschner, Florian; Aikawa, Elena; Swirski, Filip K.; Pittet, Mikael J.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Panizzi, Peter] Auburn Univ, Dept Pharmacal Sci, Harrison Sch Pharm, Auburn, AL 36849 USA. [Panizzi, Jennifer] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. [Maddur, Ashoka A.; Kroh, Heather K.; Bock, Paul E.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA. [Hackeng, Tilman M.] Univ Maastricht, Dept Biochem, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands. [Fuentes-Prior, Pablo] Hosp Santa Creu & Sant Pau, Inst Recerca, Barcelona, Spain. [Schneewind, Olaf] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu; rweissleder@mgh.harvard.edu OI Panizzi, Peter/0000-0003-0141-8807 FU US National Institutes of Health [F32-HL094010, K99-HL094533, F32DK083868, R01-HL096576, R01-HL095629, R01-EB006432, T32-CA79443, R24-CA92782, P50-CA86355, R37-HL071544, R01-HL038779]; Deutsche Herzstiftung FX We would like to thank Y. Fisher-Jeffes for review of the manuscript and C. Vinegoni, Z. Mueller and J. Sullivan for help with imaging and data analysis. We would also like to thank T. Foster for materials and helpful suggestions. This work was funded in part by grants from the US National Institutes of Health F32-HL094010, K99-HL094533 (P.P.); F32DK083868 (J.P.); R01-HL096576, R01-HL095629 (M.N.); R01-EB006432, T32-CA79443, R24-CA92782, P50-CA86355 (R.W.) and R37-HL071544, R01-HL038779 (P.E.B.) and a Deutsche Herzstiftung grant (F.L.). NR 24 TC 62 Z9 63 U1 2 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2011 VL 17 IS 9 BP 1142 EP U153 DI 10.1038/nm.2423 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 816MM UT WOS:000294605100037 PM 21857652 ER PT J AU Pattanayak, V Ramirez, CL Joung, JK Liu, DR AF Pattanayak, Vikram Ramirez, Cherie L. Joung, J. Keith Liu, David R. TI Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection SO NATURE METHODS LA English DT Article ID DNA-BINDING SPECIFICITIES; MAJOR DETERMINANT; GENE; DOMAIN; PROTEIN; CELLS; DROSOPHILA; STRATEGY; VIVO AB Engineered zinc-finger nucleases (ZFNs) are promising tools for genome manipulation, and determining off-target cleavage sites of these enzymes is of great interest. We developed an in vitro selection method that interrogates 10(11) DNA sequences for cleavage by active, dimeric ZFNs. The method revealed hundreds of thousands of DNA sequences, some present in the human genome, that can be cleaved in vitro by two ZFNs: CCR5-224 and VF2468, which target the endogenous human CCR5 and VEGFA genes, respectively. Analysis of identified sites in one cultured human cell line revealed CCR5-224-induced changes at nine off-target loci, though this remains to be tested in other relevant cell types. Similarly, we observed 31 off-target sites cleaved by VF2468 in cultured human cells. Our findings establish an energy compensation model of ZFN specificity in which excess binding energy contributes to off-target ZFN cleavage and suggest strategies for the improvement of future ZFN design. C1 [Pattanayak, Vikram; Liu, David R.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Pattanayak, Vikram; Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Ramirez, Cherie L.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA USA. [Ramirez, Cherie L.; Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ramirez, Cherie L.; Joung, J. Keith] Harvard Univ, Sch Med, Biol & Biomed Sci Program, Boston, MA 02115 USA. [Ramirez, Cherie L.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA. RP Liu, DR (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. EM drliu@fas.harvard.edu FU US National Institutes of Health (NIH) [R01 GM065400]; Defense Advanced Research Projects Agency [HR0011-11-2-0003]; Howard Hughes Medical Institute; NIH [R01 GM088040, DP1 OD006862, P30 NS045776]; Jim and Ann Orr Massachusetts General Hospital; National Science Foundation; Ford Foundation FX This research was supported by US National Institutes of Health (NIH) R01 GM065400 (D. R. L.), Defense Advanced Research Projects Agency HR0011-11-2-0003 (D. R. L.), the Howard Hughes Medical Institute (D. R. L.), NIH R01 GM088040 (J.K.J.), NIH DP1 OD006862 (J.K.J.), and the Jim and Ann Orr Massachusetts General Hospital Research Scholar award (J.K.J.). V. P. was supported by an NIH training grant to the Harvard University Training Program in Molecular, Cellular and Chemical Biology. C. L. R. was supported by a National Science Foundation Graduate Research Fellowship and a Ford Foundation Predoctoral Fellowship. The Massachusetts General Hospital Neuroscience core facility, supported by NIH P30 NS045776, provided qPCR capabilities. We thank J. Carlson, B. Dorr, C. Pattanayak, D. Reyon, J. Sander and D. Thompson for helpful discussions, M. Goodwin for technical assistance, and M. Maeder (Massachusetts General Hospital) for mammalian cell ZFN expression plasmids. NR 33 TC 221 Z9 230 U1 3 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD SEP PY 2011 VL 8 IS 9 BP 765 EP U115 DI 10.1038/nmeth.1670 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 814HL UT WOS:000294439100015 PM 21822273 ER PT J AU Vemula, PK Anderson, RR Karp, JM AF Vemula, Praveen Kumar Anderson, R. Rox Karp, Jeffrey M. TI Animal models for nickel allergy reply SO NATURE NANOTECHNOLOGY LA English DT Letter C1 [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Regenerat Therapeut, Boston, MA 02115 USA. [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Vemula, Praveen Kumar; Karp, Jeffrey M.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Anderson, R. Rox] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Laser & Cosmet Dermatol Ctr, Boston, MA 02114 USA. [Anderson, R. Rox] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Vemula, PK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Regenerat Therapeut, Boston, MA 02115 USA. EM jkarp@rics.bwh.harvard.edu NR 5 TC 0 Z9 0 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 EI 1748-3395 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD SEP PY 2011 VL 6 IS 9 BP 533 EP 533 DI 10.1038/nnano.2011.144 PG 1 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 815ST UT WOS:000294550000002 ER PT J AU Halassa, MM Siegle, JH Ritt, JT Ting, JT Feng, GP Moore, CI AF Halassa, Michael M. Siegle, Joshua H. Ritt, Jason T. Ting, Jonathan T. Feng, Guoping Moore, Christopher I. TI Selective optical drive of thalamic reticular nucleus generates thalamic bursts and cortical spindles SO NATURE NEUROSCIENCE LA English DT Article ID SLEEP; OSCILLATIONS; PATTERNS; CORTEX; SLOW AB The thalamic reticular nucleus (TRN) is hypothesized to regulate neocortical rhythms and behavioral states. Using optogenetics and multi-electrode recording in behaving mice, we found that brief selective drive of TRN switched the thalamocortical firing mode from tonic to bursting and generated state-dependent neocortical spindles. These findings provide causal support for the involvement of the TRN in state regulation in vivo and introduce a new model for addressing the role of this structure in behavior. C1 [Halassa, Michael M.; Siegle, Joshua H.; Ting, Jonathan T.; Feng, Guoping] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Halassa, Michael M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Ritt, Jason T.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Moore, Christopher I.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. RP Feng, GP (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM fengg@mit.edu; cim@mit.edu FU US National Institutes of Health [R01 NS045130-05] FX This work was partially supported by a US National Institutes of Health award (R01 NS045130-05) to C.I.M. NR 15 TC 88 Z9 89 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD SEP PY 2011 VL 14 IS 9 BP 1118 EP 1120 DI 10.1038/nn.2880 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 812ID UT WOS:000294284900010 PM 21785436 ER PT J AU Barkat, TR Polley, DB Hensch, TK AF Barkat, Tania Rinaldi Polley, Daniel B. Hensch, Takao K. TI A critical period for auditory thalamocortical connectivity SO NATURE NEUROSCIENCE LA English DT Article ID LOCAL CORTICAL CIRCUITS; IN-VITRO; CORTEX; PLASTICITY; REPRESENTATION; EXPERIENCE; RAT; BRAIN; MOUSE; ORGANIZATION AB Neural circuits are shaped by experience during periods of heightened brain plasticity in early postnatal life. Exposure to acoustic features produces age-dependent changes through largely unresolved cellular mechanisms and sites of origin. We isolated the refinement of auditory thalamocortical connectivity by in vivo recordings and day-by-day voltage-sensitive dye imaging in an acute brain slice preparation. Passive tone-rearing modified response strength and topography in mouse primary auditory cortex (A1) during a brief, 3-d window, but did not alter tonotopic maps in the thalamus. Gene-targeted deletion of a forebrain-specific cell-adhesion molecule (Icam5) accelerated plasticity in this critical period. Consistent with its normal role of slowing spinogenesis, loss of Icam5 induced precocious stubby spine maturation on pyramidal cell dendrites in neocortical layer 4 (L4), identifying a primary locus of change for the tonotopic plasticity. The evolving postnatal connectivity between thalamus and cortex in the days following hearing onset may therefore determine a critical period for auditory processing. C1 [Barkat, Tania Rinaldi; Hensch, Takao K.] Harvard Univ, Ctr Brain Sci, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Polley, Daniel B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Eaton Peabody Lab,Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Hensch, TK (reprint author), Harvard Univ, Ctr Brain Sci, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM hensch@mcb.harvard.edu OI Polley, Daniel/0000-0002-5120-2409 FU Core Research for Evolutional Science and Technology, Japan Science and Technology Agency; Human Frontiers Science Program; National Institute on Deafness and Other Communication Disorders [009836]; Harvard Society of Fellows FX Icam5-/- mice and antibody were kindly provided by M. Mishina (University of Tokyo) and Y. Yoshihara (RIKEN BSI), respectively. We thank M. Nakamura, A. Takesian, N. Gogolla, E.-J. Yang, K. Quast, M. Marcotrigiano, M. Kelly, R. Pavlyuk, B. Jones O'Brien and V. Khatri for technical assistance and comments. This work was supported by Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (T. K. H.), the Human Frontiers Science Program (T. K. H.), the National Institute on Deafness and Other Communication Disorders (grant 009836, D. B. P.) and the Harvard Society of Fellows (T.R.B.). NR 50 TC 78 Z9 81 U1 2 U2 39 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD SEP PY 2011 VL 14 IS 9 BP 1189 EP U252 DI 10.1038/nn.2882 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 812ID UT WOS:000294284900020 PM 21804538 ER PT J AU Di Lorenzo, G Buonerba, C Kantoff, PW AF Di Lorenzo, Giuseppe Buonerba, Carlo Kantoff, Philip W. TI Immunotherapy for the treatment of prostate cancer SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID ALLOGENEIC CELLULAR IMMUNOTHERAPY; PERSONALIZED PEPTIDE VACCINATION; LOADED DENDRITIC CELLS; I CLINICAL-TRIAL; SIPULEUCEL-T; PHASE-I; COMBINATION THERAPY; ANTITUMOR IMMUNITY; PROGNOSTIC-FACTORS; ACID-PHOSPHATASE AB Failure of immune surveillance has a prominent role in tumorigenesis. Cancerous cells can evade T-cell responses to tumor-associated antigens by multiple mechanisms. Active immunotherapy aims to stimulate the immune response against cancer cells. Unlike normal prostate tissue, prostate cancer is not ignored by the immune system, as shown by the presence of tumor infiltrating lymphocytes. This characteristic renders prostate cancer particularly suitable for immunotherapy. The existence of well-defined antigens, largely limited to prostate tissue, allows prostate cancer cells to be targeted without the risk of systemic autoimmune reactions, as autoimmunity specifically directed at the prostate is the goal of prostate cancer immunotherapy. Active immunotherapy directed towards prostate cancer can be conducted using multiple strategies, involving dendritic cells, whole-cell vaccines, viral vectors, DNA-based and peptide-based agents, as well as immunostimulatory agents. The only FDA-approved immunotherapy for prostate cancer is the dendritic-cell-based agent Sipuleucel-T, which yielded an advantage in overall survival, but not in progression-free survival in a phase III trial. We present the clinical developments in the field of immunotherapy and critically analyze methodological issues related to the evaluation of tumor responses to immunotherapy, trial design, and surrogate end points. C1 [Di Lorenzo, Giuseppe; Buonerba, Carlo] Univ Naples Federico 2, Dept Endocrinol & Med Oncol, Genitourinary Canc Sect, I-80132 Naples, Italy. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Di Lorenzo, G (reprint author), Univ Naples Federico 2, Dept Endocrinol & Med Oncol, Genitourinary Canc Sect, Via Pansini 5, I-80132 Naples, Italy. EM giuseppedilorenzoncol@hotmail.com NR 61 TC 46 Z9 46 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD SEP PY 2011 VL 8 IS 9 BP 551 EP 561 DI 10.1038/nrclinonc.2011.72 PG 11 WC Oncology SC Oncology GA 814AO UT WOS:000294414300007 PM 21606971 ER PT J AU Vander Heiden, MG AF Vander Heiden, Matthew G. TI Targeting cancer metabolism: a therapeutic window opens SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID TUMOR-CELL GROWTH; INTEGRATED GENOMIC ANALYSIS; FATTY-ACID SYNTHASE; PYRUVATE-KINASE M2; ATP CITRATE LYASE; GLUTAMINE-METABOLISM; BREAST-CANCER; GLUCOSE-METABOLISM; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; ONCOMETABOLITE 2-HYDROXYGLUTARATE AB Genetic events in cancer activate signalling pathways that alter cell metabolism. Clinical evidence has linked cell metabolism with cancer outcomes. Together, these observations have raised interest in targeting metabolic enzymes for cancer therapy, but they have also raised concerns that these therapies would have unacceptable effects on normal cells. However, some of the first cancer therapies that were developed target the specific metabolic needs of cancer cells and remain effective agents in the clinic today. Research into how changes in cell metabolism promote tumour growth has accelerated in recent years. This has refocused efforts to target metabolic dependencies of cancer cells as a selective anticancer strategy. C1 [Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Vander Heiden, MG (reprint author), MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. EM mvh@mit.edu FU Burrough's Wellcome Fund; Smith Family Foundation; Starr Cancer Consortium; Damon Runyon Cancer Research Foundation; US National Institutes of Health FX Thanks to D. Schenkein, L. Whitesell, B. Wolpin, K. Courtney, P. Ward and members of the Vander Heiden Laboratory for helpful discussions and comments on the manuscript. Special thanks to B. Bevis and S. Y. Lunt for advice and help with the generation of the figures. The author acknowledges support from the Burrough's Wellcome Fund, the Smith Family Foundation, the Starr Cancer Consortium, the Damon Runyon Cancer Research Foundation and the US National Institutes of Health. NR 171 TC 329 Z9 331 U1 23 U2 144 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 EI 1474-1784 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2011 VL 10 IS 9 BP 671 EP 684 DI 10.1038/nrd3504 PG 14 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 814TC UT WOS:000294479100020 PM 21878982 ER PT J AU Doria, A Krolewski, AS AF Doria, Alessandro Krolewski, Andrzej S. TI Lowering serum uric acid levels to prevent kidney failure SO NATURE REVIEWS NEPHROLOGY LA English DT News Item ID RENAL-DISEASE; ALLOPURINOL; PROGRESSION; RISK C1 [Doria, Alessandro; Krolewski, Andrzej S.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu NR 10 TC 4 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD SEP PY 2011 VL 7 IS 9 BP 495 EP 496 DI 10.1038/nrneph.2011.107 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 814BO UT WOS:000294420000005 PM 21808278 ER PT J AU Mi, LZ Lu, CF Li, ZL Nishida, N Walz, T Springer, TA AF Mi, Li-Zhi Lu, Chafen Li, Zongli Nishida, Noritaka Walz, Thomas Springer, Timothy A. TI Simultaneous visualization of the extracellular and cytoplasmic domains of the epidermal growth factor receptor SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; EGF RECEPTOR; CRYSTAL-STRUCTURE; LUNG-CANCER; ACTIVATION; BINDING; INTERNALIZATION; INHIBITOR; THREONINE; MECHANISM AB To our knowledge, no structural study to date has characterized, in an intact receptor, the coupling of conformational change in extracellular domains through a single-pass transmembrane domain to conformational change in cytoplasmic domains. Here we examine such coupling, and its unexpected complexity, using nearly full-length epidermal growth factor receptor (EGFR) and negative-stain EM. The liganded, dimeric EGFR ectodomain can couple both to putatively active, asymmetrically associated kinase dimers and to putatively inactive, symmetrically associated kinase dimers and monomers. Inhibitors that stabilize the active or inactive conformation of the kinase active site, as well as mutations in the kinase dimer interface and a juxtamembrane phosphorylation site, shift the equilibrium among the three kinase association states. This coupling of one conformation of an activated receptor ectodomain to multiple kinase-domain arrangements reveals previously unanticipated complexity in transmembrane signaling and facilitates regulation of receptor function in the juxtamembrane and cytoplasmic environments. C1 [Mi, Li-Zhi; Lu, Chafen; Springer, Timothy A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Mi, Li-Zhi; Lu, Chafen; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Li, Zongli; Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Li, Zongli; Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Nishida, Noritaka] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo, Japan. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. EM springer@idi.harvard.edu RI Mi, Li-Zhi/B-1371-2016 OI Mi, Li-Zhi/0000-0001-9907-5245 FU US National Institutes of Health [HL-48675] FX This work was supported by US National Institutes of Health grant HL-48675. L.-Z.M., C. L. and T. A. S. thank J. Kuriyan for hosting them in 2004-2005 when experiments that eventually led to this work were initiated. NR 29 TC 52 Z9 52 U1 2 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD SEP PY 2011 VL 18 IS 9 BP 984 EP U1502 DI 10.1038/nsmb.2092 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 815TB UT WOS:000294551200005 PM 21822280 ER PT J AU Scripko, PD Greer, DM AF Scripko, Patricia D. Greer, David M. TI An Update on Brain Death Criteria A Simple Algorithm With Complex Questions SO NEUROLOGIST LA English DT Review DE brain death; coma; apnea; ancillary testing; prognosis; practice parameters ID GUILLAIN-BARRE-SYNDROME; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; STEM DEATH; TRANSCRANIAL DOPPLER; MR-ANGIOGRAPHY; CT ANGIOGRAPHY; DIAGNOSIS; MOVEMENTS; REFLEXES; PATIENT AB Brain death criteria have been based on 3 cardinal features throughout history: coma, brainstem areflexia, and apnea, and thus have undergone little change. In 1995, the American Academy of Neurology (AAN) detailed these criteria in a step-by-step fashion that included meeting prerequisites, performing the clinical examination, performing ancillary testing, and documentation. Fifteen years later, many questions still remain regarding the diagnosis of brain death. The Quality Standards Subcommittee of the AAN sought to answer 5 of these outstanding questions. Ultimately, their data supported the utility of the 1995 criteria and warned against the use of new technologies before proper validation. This review briefly tells the story of brain death criteria, making mention of the steps outlined by the AAN in 1995 and discussing the recent evidence released by the Quality Standards Subcommittee in the new 2010 Practice Parameter Update. C1 [Greer, David M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. [Scripko, Patricia D.] Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Greer, DM (reprint author), Yale Univ, Sch Med, Dept Neurol, LLCI 708,15 York St, New Haven, CT 06520 USA. EM david.greer@yale.edu NR 57 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD SEP PY 2011 VL 17 IS 5 BP 237 EP 240 DI 10.1097/NRL.0b013e318224edfa PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 814PD UT WOS:000294468300001 PM 21881464 ER PT J AU Salinsky, M Spencer, D Boudreau, E Ferguson, F AF Salinsky, Martin Spencer, David Boudreau, Eilis Ferguson, Felicia TI Psychogenic nonepileptic seizures in US veterans SO NEUROLOGY LA English DT Article ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; VIDEO-EEG; EPILEPSY; DIAGNOSIS; ATTACKS; IRAQ AB Objectives: Psychogenic nonepileptic seizures (PNES) are frequently encountered in epilepsy monitoring units (EMU) and can result in significant long-term disability. We reviewed our experience with veterans undergoing seizure evaluation in the EMU to determine the time delay to diagnosis of PNES, the frequency of PNES, and cumulative antiepileptic drug (AED) treatment. We compared veterans with PNES to civilians with PNES studied in the same EMU. Methods: We reviewed records of all patients admitted to one Veterans Affairs Medical Center (VAMC) EMU over a 10-year interval. These patients included 203 veterans and 726 civilians from the university affiliate. The percentage of patients with PNES was calculated for the veteran and civilian groups. Fifty veterans with only PNES were identified. Each veteran with PNES was matched to the next civilian patient with PNES. The 2 groups were compared for interval from onset of the habitual spells to EMU diagnosis, cumulative AED treatment, and other measures. Results: PNES were identified in 25% of veterans and 26% of civilians admitted to the EMU. The delay from onset of spells to EMU diagnosis averaged 60.5 months for veterans and 12.5 months for civilians (p < 0.001). Cumulative AED treatment was 4 times greater for veterans with PNES as compared to civilians (p < 0.01). Fifty-eight percent of veterans with PNES were thought to have seizures related to traumatic brain injury. Conclusions: The results indicate a substantial delay in the diagnosis of PNES in veterans as compared to civilians. The delay is associated with greater cumulative AED treatment. Neurology (R) 2011;77:945-950 C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Salinsky, M (reprint author), 3181 SW Sam Jackson Pk Rd,CR-120, Portland, OR 97239 USA. EM Salinsky@ohsu.edu FU NIH (NIDA, NIAAA) FX Dr. Salinsky serves on speakers' bureaus for UCB and Pfizer Inc and has served on scientific advisory boards for and received honoraria from Medtronic, Inc., Cyberonics Inc., and Lundbeck Inc. Dr. Spencer has served on the speakers' bureau of and received honoraria from UCB; serves as Patient Page Editor for Neurology (R), Chief Editor for EMedicine, Associate Editor for the Journal of Behavior and Brain Science, and on the Professional Advisory Board for Neurology Now; has received research support from NeuroPace, Inc.; and holds stock in StemCells, Inc. Dr. Boudreau serves on the editorial board of Aviation, Space, and Environmental Medicine; and has received research support from the NIH (NIDA, NIAAA). Dr. Ferguson reports no disclosures. NR 28 TC 29 Z9 29 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 2011 VL 77 IS 10 BP 945 EP 950 DI 10.1212/WNL.0b013e31822cfc46 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 815PR UT WOS:000294538100011 PM 21893668 ER PT J AU Sankaran, VG Xu, J Byron, R Greisman, HA Fisher, C Weatherall, DJ Sabath, DE Groudine, M Orkin, SH Premawardhena, A Bender, MA AF Sankaran, Vijay G. Xu, Jian Byron, Rachel Greisman, Harvey A. Fisher, Chris Weatherall, David J. Sabath, Daniel E. Groudine, Mark Orkin, Stuart H. Premawardhena, Anuja Bender, M. A. TI A Functional Element Necessary for Fetal Hemoglobin Silencing SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DELTA-BETA-THALASSEMIA; GAMMA-GLOBIN GENE; SICKLE-CELL-DISEASE; FACTOR KLF1 CAUSES; HEREDITARY PERSISTENCE; SRI-LANKA; BCL11A; EXPRESSION; DELETION; SEQUENCES AB Background An improved understanding of the regulation of the fetal hemoglobin genes holds promise for the development of targeted therapeutic approaches for fetal hemoglobin induction in the beta-hemoglobinopathies. Although recent studies have uncovered trans-acting factors necessary for this regulation, limited insight has been gained into the cis-regulatory elements involved. Methods We identified three families with unusual patterns of hemoglobin expression, suggestive of deletions in the locus of the beta-globin gene (beta-globin locus). We performed array comparative genomic hybridization to map these deletions and confirmed breakpoints by means of polymerase-chain-reaction assays and DNA sequencing. We compared these deletions, along with previously mapped deletions, and studied the trans-acting factors binding to these sites in the beta-globin locus by using chromatin immunoprecipitation. Results We found a new (delta beta)(0)-thalassemia deletion and a rare hereditary persistence of fetal hemoglobin deletion with identical downstream breakpoints. Comparison of the two deletions resulted in the identification of a small intergenic region required for gamma-globin (fetal hemoglobin) gene silencing. We mapped a Kurdish beta(0)-thalassemia deletion, which retains the required intergenic region, deletes other surrounding sequences, and maintains fetal hemoglobin silencing. By comparing these deletions and other previously mapped deletions, we elucidated a 3.5-kb intergenic region near the 5' end of the delta-globin gene that is necessary for gamma-globin silencing. We found that a critical fetal hemoglobin silencing factor, BCL11A, and its partners bind within this region in the chromatin of adult erythroid cells. Conclusions By studying three families with unusual deletions in the beta-globin locus, we identified an intergenic region near the delta-globin gene that is necessary for fetal hemoglobin silencing. (Funded by the National Institutes of Health and others.) C1 [Sankaran, Vijay G.; Xu, Jian; Orkin, Stuart H.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Xu, Jian; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sankaran, Vijay G.] Broad Inst, Cambridge, MA USA. [Byron, Rachel; Groudine, Mark; Bender, M. A.] Fred Hutchinson Canc Ctr, Seattle, WA 98109 USA. [Greisman, Harvey A.; Sabath, Daniel E.; Bender, M. A.] Univ Washington, Seattle, WA 98195 USA. [Fisher, Chris; Weatherall, David J.] Weatherall Inst Mol Med, Oxford, England. [Premawardhena, Anuja] Univ Kelaniya, Ragama Gampaha, Sri Lanka. RP Sankaran, VG (reprint author), Childrens Hosp, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM sankaran@broadinstitute.org; mbender@fhcrc.org FU Cooley's Anemia Foundation; National Institutes of Health [DK44746, HL032259]; Howard Hughes Medical Institute; Wellcome Trust; March of Dimes FX Supported by grants from the Cooley's Anemia Foundation (to Dr. Sankaran), the National Institutes of Health (DK44746, to Drs. Bender and Groudine, and HL032259, to Dr. Orkin), the Howard Hughes Medical Institute (to Drs. Xu and Orkin), and the Wellcome Trust and March of Dimes (to Dr. Weatherall). NR 30 TC 74 Z9 75 U1 4 U2 11 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 SEP 1 PY 2011 VL 365 IS 9 BP 807 EP 814 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 813YC UT WOS:000294405200007 PM 21879898 ER PT J AU Herrera, AF Soriano, G Bellizzi, AM Hornick, JL Ho, VT Ballen, KK Baden, LR Cutler, CS Antin, JH Soiffer, RJ Marty, FM AF Herrera, Alex F. Soriano, Gabriela Bellizzi, Andrew M. Hornick, Jason L. Ho, Vincent T. Ballen, Karen K. Baden, Lindsey R. Cutler, Corey S. Antin, Joseph H. Soiffer, Robert J. Marty, Francisco M. TI Cord Colitis Syndrome in Cord-Blood Stem-Cell Transplantation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; UNRELATED DONORS; CHRONIC GRAFT; HEMATOLOGIC MALIGNANCIES; MYCOPHENOLATE-MOFETIL; HEPATIC COMPLICATIONS; PERIPHERAL-BLOOD; ADULT PATIENTS; RECIPIENTS AB Background Diarrhea is a frequent complication of hematopoietic stem-cell transplantation (HSCT). Important causes of diarrhea after HSCT include acute graft-versus-host disease (GVHD), infections, and medications. After the transplantation and engraftment of hematopoietic stem cells from umbilical-cord blood, we observed a new syndrome of culture-negative, antibiotic-responsive diarrhea not attributable to any known cause. Methods We conducted a retrospective cohort study of all patients undergoing cord-blood HSCT at our center between March 2003 and March 2010. The cord colitis syndrome was defined as a persistent diarrheal illness in such patients that was not due to acute GVHD, viral or bacterial infection, or another identifiable cause. Clinical and histopathological features of patients meeting the case definition were further analyzed. Results Among 104 patients who underwent cord-blood HSCT at our center, the cord colitis syndrome developed in 11 (10.6%). The 1-year Kaplan-Meier cumulative probability of meeting the case definition for the syndrome was 0.16. The median time to onset after transplantation was 131 days (range, 88 to 314). All patients had a response to a 10-to-14-day course of empirical therapy with metronidazole, alone or in combination with a fluoroquinolone. Five of the 11 patients (45%) had recurrent diarrhea shortly after discontinuation of antibiotics, and all patients who had a relapse had a response to reinitiation of antibiotic therapy. On histologic examination, all patients with the cord colitis syndrome had chronic active colitis, with granulomatous inflammation present in 7 of 11 patients (64%). Conclusions The cord colitis syndrome is clinically and histopathologically distinct from acute GVHD and other causes of diarrhea in patients who have undergone cord-blood HSCT and is relatively common in this patient population. The syndrome should be considered in such patients who have diarrhea that is not attributable to other causes. C1 [Herrera, Alex F.; Soriano, Gabriela] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Bellizzi, Andrew M.; Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Baden, Lindsey R.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Ho, Vincent T.; Cutler, Corey S.; Antin, Joseph H.; Soiffer, Robert J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. RP Herrera, AF (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM afherrera@partners.org NR 34 TC 26 Z9 26 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 1 PY 2011 VL 365 IS 9 BP 815 EP 824 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 813YC UT WOS:000294405200008 PM 21879899 ER PT J AU Chamarthi, B Greene, MF Dluhy, RG AF Chamarthi, Bindu Greene, Michael F. Dluhy, Robert G. TI A Problem in Gestation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PRIMARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE; HUMAN-PREGNANCY; CALCIUM; PANCREATITIS; METABOLISM; PEPTIDE C1 [Chamarthi, Bindu; Dluhy, Robert G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Greene, Michael F.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Chamarthi, B (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM bchamarthi@partners.org NR 15 TC 2 Z9 3 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 SEP 1 PY 2011 VL 365 IS 9 BP 843 EP 848 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 813YC UT WOS:000294405200013 PM 21879903 ER PT J AU Walcott, BP Kahle, KT AF Walcott, Brian P. Kahle, Kristopher T. TI Blast-Related Traumatic Brain Injury in U.S. Military Personnel SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Walcott, Brian P.; Kahle, Kristopher T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu NR 3 TC 0 Z9 0 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 SEP 1 PY 2011 VL 365 IS 9 BP 860 EP 860 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 813YC UT WOS:000294405200018 PM 21879908 ER PT J AU Sharma, N Franco, RA AF Sharma, Nutan Franco, Ramon A., Jr. TI Consideration of Genetic Contributions to the Risk for Spasmodic Dysphonia SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation-and- OTO-EXPO CY SEP 25-29, 2010 CL Boston, MA SP Amer Acad Otolaryngol Head & Neck Surg Fdn, UMDNJ-New Jersey Med Sch DE spasmodic dysphonia; dystonia; genetics ID PRIMARY DYSTONIA; ASSOCIATION; HAPLOTYPE; DYT1 AB Spasmodic dysphonia, a form of the neurologic condition known as dystonia, results from involuntary spasms of the larynx, producing interruptions of speech and changes in voice quality. The pathogenesis of spasmodic dysphonia is not well understood. However, several genetic mutations have been identified that cause different forms of dystonia. In some individuals, these genetic mutations result in spasmodic dysphonia, either with no other signs of dystonia or as part of a broader dystonia phenotype. Thus, research in the growing field of dystonia genetics may help to inform our understanding of the pathogenesis of spasmodic dysphonia. C1 [Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Franco, Ramon A., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Sharma, N (reprint author), 149 13th St,Rm 6407, Charlestown, MA 02129 USA. EM nsharma@partners.org NR 10 TC 2 Z9 2 U1 3 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2011 VL 145 IS 3 BP 369 EP 370 DI 10.1177/0194599811411656 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 814OY UT WOS:000294467700003 PM 21636841 ER PT J AU Kieff, D Fink, D AF Kieff, David Fink, Daniel TI Decontamination of Nasal Atomizer Tips: Alcohol versus Guards SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation-and- OTO-EXPO CY SEP 25-29, 2010 CL Boston, MA SP Amer Acad Otolaryngol Head & Neck Surg Fdn, UMDNJ-New Jersey Med Sch DE atomizer; culture; tip guard; isopropanol; rhinology ID BACTERIAL-CONTAMINATION; RISK AB Objective. To determine the efficacy of wiping the nasal atomizer tip with 70% isopropanol versus using single-use plastic atomizer tip guards in preventing cross-contamination. Study Design. Single-center, prospective, partially blinded, alternating double-arm trial. Setting. Specialty-specific otolaryngology emergency room. Methods. Thirty-four consecutive patients who presented to an emergency room received nasal anesthetic with a Venturi atomizer. The atomizers for one half of patients were cleaned with an isopropyl alcohol pad immediately after use (group A). The atomizers for the other half were used with a sterile tip cover in place (group B). The effectiveness of 2 different methods in preventing contamination of the atomizer tip was compared. Results. One of the 17 atomizers from group A was contaminated (5.9%); 15 of the 17 atomizers from group B were contaminated (88.2%). This represents a difference of 82.3%, or a risk ratio of 15: 1 against the use of nasal tip guards (P = .000002). Conclusions. Venturi atomizer tips frequently become contaminated despite the use of a sterile tip cover. This happens at a dramatically decreased rate with the use of isopropyl alcohol for cleaning. Clinical significance of this contamination is uncertain. C1 [Kieff, David; Fink, Daniel] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kieff, D (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, 243 Charles S, Boston, MA 02114 USA. EM david_kieff@meei.harvard.edu NR 8 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2011 VL 145 IS 3 BP 411 EP 413 DI 10.1177/0194599811404318 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 814OY UT WOS:000294467700009 PM 21493261 ER PT J AU Chapuy, CI Annino, DJ Snavely, A Li, Y Tishler, RB Norris, CM Haddad, RI Goguen, LA AF Chapuy, Claudia I. Annino, Donald J. Snavely, Anna Li, Yi Tishler, Roy B. Norris, Charles M. Haddad, Robert I. Goguen, Laura A. TI Swallowing Function following Postchemoradiotherapy Neck Dissection: Review of Findings and Analysis of Contributing Factors SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation-and- OTO-EXPO CY SEP 25-29, 2010 CL Boston, MA SP Amer Acad Otolaryngol Head & Neck Surg Fdn, UMDNJ-New Jersey Med Sch DE head and neck cancer; dysphagia; neck dissection; chemoradiation ID SQUAMOUS-CELL CARCINOMA; LOCALLY ADVANCED HEAD; LONG-TERM DYSPHAGIA; QUALITY-OF-LIFE; CONCURRENT CHEMORADIATION; DEFINITIVE RADIOTHERAPY; RADIATION-THERAPY; CANCER; CHEMOTHERAPY; ASPIRATION AB Objective. This study assesses swallowing function following chemoradiotherapy and neck dissection in head and neck cancer patients and investigates clinical, treatment, and neck dissection factors associated with dysphagia. Study Design. Case series with chart review. Setting. Tertiary care center. Subjects and Methods. Eighty-eight patients undergoing neck dissection after chemoradiotherapy for advanced head and neck cancer were reviewed. Dysphagia outcome measures included weight loss, diet, gastrostomy tube (GT) dependency, and video swallow findings of aspiration or stenosis. In addition, the researchers created a Diet/GT Scale, with scores ranging from 1 to 5. Univariate and multivariate analysis of clinical, treatment, or neck dissection factors potentially associated with dysphagia outcome measures was undertaken. Results. Peak mean weight loss was 17% at 6 months after chemoradiotherapy. At 12 months, a soft/regular diet was taken by 78 of 88 patients (89%), and only 1 of 88 patients (1%) was nil per os. Gastrostomy tube dependence at 6, 12, and 24 months was 53%, 25%, and 10%, respectively. The Diet/GT score was 5 (gastrostomy tube removed and soft/regular diet) for 47% at 6 months, 74% at 12 months, and 89% at 24 months. Multivariate analyses revealed that higher tumor stage was associated with a lower Diet/GT score at 12 months (P = .02) and gastrostomy dependence at 12 months (P = .01) and 24 months (P = .04). Conclusion. Despite the addition of neck dissection to chemoradiotherapy, nearly all patients took a soft or regular diet and reached a Diet/GT score of 5, and only 1% remained nil per os. A higher tumor stage is associated with a lower Diet/GT score and gastrostomy tube dependency beyond 12 months. C1 [Annino, Donald J.; Norris, Charles M.; Goguen, Laura A.] Brigham & Womens Hosp, Dept Surg, Div Otolaryngol, Boston, MA 02115 USA. [Chapuy, Claudia I.; Haddad, Robert I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Snavely, Anna; Li, Yi] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Tishler, Roy B.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Goguen, LA (reprint author), Brigham & Womens Hosp, Dept Surg, Div Otolaryngol, Boston, MA 02115 USA. EM lgoguen@partners.org FU NCI NIH HHS [T32 CA009337] NR 30 TC 7 Z9 7 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2011 VL 145 IS 3 BP 428 EP 434 DI 10.1177/0194599811403075 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 814OY UT WOS:000294467700013 PM 21493276 ER PT J AU DePoortere, D Kofonow, JM Chen, B Chiu, AG Cohen, NA AF DePoortere, David Kofonow, Jennifer M. Chen, Bei Chiu, Alexander G. Cohen, Noam A. TI Murine Ciliotoxicity and Rabbit Sinus Mucosal Healing by Polyhydrated Ionogen SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery-Foundation-and- OTO-EXPO CY SEP 25-29, 2010 CL Boston, MA SP Amer Acad Otolaryngol Head & Neck Surg Fdn, UMDNJ-New Jersey Med Sch DE mucosal wound healing; polyhydrated ionogen; inflammation; cytokines; matrix metalloproteases; ciliotoxicity ID CILIARY BEAT FREQUENCY; SURFACE RESPIRATORY EPITHELIUM; WOUND REPAIR; MUCOCILIARY TRANSPORT; MAXILLARY SINUS; ANIMAL-MODEL; SURGERY; NASAL; INTERFACE; EFFICACY AB Objectives. Determine the toxicity and efficacy of a novel antiprotease topical irrigation, polyhydrated ionogen (PHI) +/- MgBr(2), in improving sinonasal remucosalization following surgery. Study Design. Blinded, randomized controlled study. Setting. Academic. Subjects and Methods. Ciliary beat frequency (CBF) of murine nasal septal explants was continuously recorded before and after addition of PHI solution to asses for ciliotoxicity. To evaluate for efficacy in remucosalization, 9 New Zealand white rabbits underwent bilateral medial-wall maxillary mucosal stripping followed by placement of an indwelling irrigation catheter. In a randomized fashion one side received 3 mL of normal saline (NS) daily, whereas the contralateral side received PHI +/- MgBr(2). Following a 14-day therapeutic trial, remucosalization was assessed by hematoxylin and eosin staining and immunohistochemistry for beta-tubulin, a marker of cilia. A semiquantitative grading of ciliated remucosalization was applied with a chi-square test to compare the saline with the PHI +/- MgBr(2) treatment. Results. Safety evaluation of the PHI solutions demonstrated no evidence of ciliotoxicity. Histologic semiquantitative analysis of maxillary sinus remucosalization demonstrated significantly more ciliated epithelium (> 60%) in the majority of PHI (n = 4) and PHI with MgBr(2) (n = 5) treatment compared with the saline treatment (< 30%) (n = 9). This was confirmed with immunohistochemical staining for type IV beta-tubulin a marker of respiratory cilia. Conclusions. Success of functional endoscopic sinus surgery depends on restoration of normal mucociliary clearance. Topical PHI application has previously been demonstrated to significantly increase dermal wound healing. PHI solution is not ciliotoxic, and daily topical PHI or PHI MgBr(2) irrigation enhances ciliated remucosalization compared with saline. C1 [DePoortere, David; Kofonow, Jennifer M.; Chen, Bei; Chiu, Alexander G.; Cohen, Noam A.] Univ Penn, Sch Med, Dept Otorhinolaryngol, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia VA Med Ctr, Dept Otorhinolaryngol, Philadelphia, PA USA. RP Cohen, NA (reprint author), Ravdin Bldg,5th Floor, Philadelphia, PA 19104 USA. EM cohenn@uphs.upenn.edu RI Chiu, Alexander/J-1230-2014; OI Chiu, Alexander/0000-0002-7592-6575; Cohen, Noam/0000-0002-9462-3932 NR 30 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2011 VL 145 IS 3 BP 482 EP 488 DI 10.1177/0194599811399558 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 814OY UT WOS:000294467700022 PM 21493328 ER PT J AU Rajabi, H Joshi, MD Jin, CN Ahmad, R Kufe, D AF Rajabi, Hasan Joshi, Maya Datt Jin, Caining Ahmad, Rehan Kufe, Donald TI Androgen Receptor Regulates Expression of the MUC1-C Oncoprotein in Human Prostate Cancer Cells SO PROSTATE LA English DT Article DE prostate cancer; androgen-dependence; MUC1; androgen receptor; miR-125b ID NF-KAPPA-B; BETA-CATENIN; CONSTITUTIVE ACTIVATION; MUCIN 1; TRANSCRIPTION FACTOR; INDEPENDENT GROWTH; CARCINOMA-CELLS; GENE; BREAST; PROGRESSION AB BACKGROUND. The MUC1 heterodimeric oncoprotein is aberrantly overexpressed in human prostate cancers with more aggressive pathologic and clinical features. However, the signals that regulate MUC1 expression in prostate cancer cells are not well understood. METHODS. MUC1 expression was studied in androgen-dependent and -independent prostate cancer cell lines by quantitative RT-PCR, immunoblotting and assessment of MUC1 promoter activation. Chromatin immunoprecipitation (ChIP) studies were performed to assess androgen receptor (AR) occupancy on the MUC1 promoter. Post-transcriptional regulation of MUC1 expression was assessed by miR-125b-mediated effects on activity of the MUC1 3' untranslated region (3'UTR). RESULTS. The present studies demonstrate that AR occupies a consensus AR element on the MUC1 promoter in androgen-dependent LNCa P, but not in androgen-independent DU145 and PC3, prostate cancer cells. The results further show that AR downregulates MUC1 gene transcription. Stable introduction of exogenous AR in PC3 (PC3/AR) cells and then silencing of AR confirmed AR-mediated repression of the MUC1 promoter. AR signaling has also been shown to drive miR-125b expression. The present studies further demonstrate that miR-125b suppresses MUC1 translation in LNCaP cells and that an anti-sense miR-125b upregulates expression of MUC1 protein. In addition, stable expression of miR-125b in DU145 cells resulted in decreases in MUC1 levels. CONCLUSIONS. These findings demonstrate that AR signaling regulates MUC1 expression by transcriptional and posttranscriptional mechanisms in prostate cancer cells. Prostate 71: 1299-1308, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Rajabi, Hasan; Joshi, Maya Datt; Jin, Caining; Ahmad, Rehan; Kufe, Donald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 830, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU Department of Defense [W81XWH-08-1-0093] FX Grant sponsor: Department of Defense Prostate Cancer Idea Award; Grant number: W81XWH-08-1-0093. NR 49 TC 18 Z9 22 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD SEP 1 PY 2011 VL 71 IS 12 BP 1299 EP 1308 DI 10.1002/pros.21344 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 814JB UT WOS:000294443600006 PM 21308711 ER PT J AU Niu, YN Ge, RB Hu, LB Diaz, C Wang, ZW Wu, CL Olumi, AF AF Niu, Yinong Ge, Rongbin Hu, Libing Diaz, Christian Wang, Zongwei Wu, Chin-Lee Olumi, Aria F. TI Reduced Levels of 5-alpha Reductase 2 in Adult Prostate Tissue and Implications for BPH Therapy SO PROSTATE LA English DT Article DE prostate; 5-alpha reductase; resistance to therapy ID CANCER PREVENTION TRIAL; MALE PSEUDOHERMAPHRODITISM; GENE-EXPRESSION; DNA METHYLATION; FINASTERIDE; HYPERPLASIA; AGE; EPIGENETICS; ANTIGEN; MUSCLE AB BACKGROUND. 5-alpha reductase 2 (5-AR 2) is a key enzyme that is responsible of proper development of prostate tissue. Inhibition of 5-AR 2 has proven to be efficacious for management of urinary symptoms secondary benign prostatic hyperplasia (BPH). However, some patients are resistant to the therapeutic effects of 5-AR 2 inhibitor. We wished to determine why some benign non-cancerous adult human prostates do not express 5-AR 2, and hypothesized that methylation of 5-AR 2 promoter region correlated with low expression of 5-AR 2 protein. METHODS. The transition zone of 42 human prostate tissues after radical prostatectomy was used for evaluation. Initially, 21 paraffin embedded samples were used to assess immunoreactivity to 5-AR 2 antibody in non-cancerous BPH samples. In the next 21 samples, fresh frozen prostate transition zone samples without cancer were assessed for immunoreactivity and methylation of the 5-AR 2 promoter using methyl-specific PCR. RESULTS. We show that 6/21 (29%) of benign human prostate samples did not express the 5-AR 2 protein. Moreover, the promoter region of 5-AR 2 contains a CpG island that is methylated in benign prostate epithelial cells in culture and also in 39% (7/18) human prostate tissues. We show a strong correlation between methylation of the 5-AR 2 promoter region and absence of 5-AR 2 protein expression (P = 0.0025, Fisher's exact test). CONCLUSIONS. Methylation of 5-AR 2 promoter may account for low or absent expression of 5-AR 2 in some human adult prostate tissues. Prostate 71: 1317-1324, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Niu, Yinong; Ge, Rongbin; Hu, Libing; Diaz, Christian; Wang, Zongwei; Wu, Chin-Lee; Olumi, Aria F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. [Niu, Yinong] Capital Med Univ, Beijing Chaoyang Hosp, Dept Urol, Beijing, Peoples R China. [Wu, Chin-Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Olumi, AF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Yawkey Bldg,Suite 7E, Boston, MA 02114 USA. EM aolumi@partners.org FU Bertucci Prostate Research Foundation at Massachusetts General Hospital; China Scholarship Council FX Grant sponsor: Bertucci Prostate Research Foundation at Massachusetts General Hospital to AFO and support from China Scholarship Council to YN. NR 36 TC 13 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD SEP 1 PY 2011 VL 71 IS 12 BP 1317 EP 1324 DI 10.1002/pros.21348 PG 8 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 814JB UT WOS:000294443600008 PM 21308715 ER PT J AU Wen, F Sethi, DK Wucherpfennig, KW Zhao, HM AF Wen, Fei Sethi, Dhruv K. Wucherpfennig, Kai W. Zhao, Huimin TI Cell surface display of functional human MHC class II proteins: yeast display versus insect cell display SO PROTEIN ENGINEERING DESIGN & SELECTION LA English DT Article DE directed evolution; DR2myelin basic protein (MBP); insect cell display; major histocompatibility complex (MHC); yeast display ID MAJOR HISTOCOMPATIBILITY COMPLEX; ALPHA-BETA-HETERODIMERS; MYELIN BASIC-PROTEIN; T-CELLS; PEPTIDE COMPLEXES; ANTIGENIC PEPTIDE; IN-VIVO; DIRECTED EVOLUTION; ANTITUMOR IMMUNITY; BINDING AB Reliable and robust systems for engineering functional major histocompatibility complex class II (MHCII) proteins have proved elusive. Availability of such systems would enable the engineering of peptide-MHCII (pMHCII) complexes for therapeutic and diagnostic applications. In this paper, we have developed a system based on insect cell surface display that allows functional expression of heterodimeric DR2 molecules with or without a covalently bound human myelin basic protein (MBP) peptide, which is amenable to directed evolution of DR2MBP variants with improved T cell receptor (TCR)-binding affinity. This study represents the first example of functional display of human pMHCII complexes on insect cell surface. In the process of developing this pMHCII engineering system, we have also explored the potential of using yeast surface display for the same application. Our data suggest that yeast display is a useful system for analysis and engineering of peptide binding of MHCII proteins, but not suitable for directed evolution of pMHC complexes that bind with low affinity to self-reactive TCRs. C1 [Wen, Fei; Zhao, Huimin] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA. [Sethi, Dhruv K.; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Sethi, Dhruv K.; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zhao, Huimin] Univ Illinois, Inst Genom Biol, Dept Biochem, Urbana, IL 61801 USA. [Zhao, Huimin] Univ Illinois, Inst Genom Biol, Dept Chem, Urbana, IL 61801 USA. [Zhao, Huimin] Univ Illinois, Inst Genom Biol, Dept Bioengn, Urbana, IL 61801 USA. RP Zhao, HM (reprint author), Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL 61801 USA. EM zhao5@illinois.edu FU Department of Chemical and Biomolecular Engineering of the University of Illinois at Urbana-Champaign; National Institutes of Health [PO1 AI045757, R01AI054520] FX This work was supported by the Department of Chemical and Biomolecular Engineering of the University of Illinois at Urbana-Champaign and grants from the National Institutes of Health to K. W. W. (PO1 AI045757, R01AI054520). NR 46 TC 9 Z9 10 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-0126 J9 PROTEIN ENG DES SEL JI Protein Eng. Des. Sel. PD SEP PY 2011 VL 24 IS 9 SI SI BP 701 EP 709 DI 10.1093/protein/gzr035 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 815UP UT WOS:000294555600010 PM 21752831 ER PT J AU Sajatovic, M Dawson, NV Perzynski, AT Blixen, CE Bialko, CS McKibbin, CL Bauer, MS Seeholzer, EL Kaiser, D Fuentes-Casiano, E AF Sajatovic, Martha Dawson, Neal V. Perzynski, Adam T. Blixen, Carol E. Bialko, Christopher S. McKibbin, Christine L. Bauer, Mark S. Seeholzer, Eileen L. Kaiser, Denise Fuentes-Casiano, Edna TI Optimizing Care for People With Serious Mental Illness and Comorbid Diabetes SO PSYCHIATRIC SERVICES LA English DT Article ID WEIGHT MANAGEMENT PROGRAM; SCHIZOPHRENIA; TRIAL AB Diabetes and obesity among patients with serious mental illness are common. Use of second-generation antipsychotics compounds risk, and widely prevalent unhealthy behaviors further contribute to negative outcomes. This column describes Targeted Training in Illness Management, a group-based psychosocial treatment that blends psychoeducation, problem identification, goal setting, and behavioral modeling and reinforcement. The intervention has been adapted to the primary care setting and is targeted at individuals with serious mental illness and diabetes. A key feature of the intervention is the use of peer educators with serious mental illness and diabetes to teach and model self-management. Promising results from a 16-week trial are reported. (Psychiatric Services 62:1001-1003, 2011) C1 [Sajatovic, Martha; Bialko, Christopher S.; Fuentes-Casiano, Edna] Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. [Dawson, Neal V.; Perzynski, Adam T.; Blixen, Carol E.; Seeholzer, Eileen L.; Kaiser, Denise] Case Western Reserve Univ, Ctr Hlth Care Res & Policy, Cleveland, OH 44106 USA. [McKibbin, Christine L.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Bauer, Mark S.] Boston Healthcare Syst, Dept Vet Affairs, Boston, MA USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Boston, MA USA. RP Sajatovic, M (reprint author), Case Western Reserve Univ, Sch Med, Dept Psychiat, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM martha.sajatovic@uhhospitals.org RI Sajatovic, Martha/I-8001-2014; OI Perzynski, Adam/0000-0002-1323-0353 FU Case Western Reserve University (CWRU) School of Medicine; Department of Psychiatry, University Hospitals Case Medical Center; CWRU [UL1RR024989]; GlaxoSmithKline; AstraZeneca; Pfizer; Merck; Ortho-McNeil Janssen FX This study was supported by a Bridge Funds grant from Case Western Reserve University (CWRU) School of Medicine and the Department of Psychiatry, University Hospitals Case Medical Center, and by grant UL1RR024989 from CWRU Clinical and Translational Science Awards (CTSA). The CTSA is a component of the National Institute of Health (NIH) and NIH Roadmap for Medical Research. The contents of this report do not necessarily represent the official view of the National Center for Research Resources or the NIH.; Dr. Sajatovic has received research grants from GlaxoSmithKline, AstraZeneca, Pfizer, Merck, and Ortho-McNeil Janssen; she is a consultant to the Cognition Group and to United Biosource Corp. The other authors report no competing interests. NR 8 TC 16 Z9 16 U1 0 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2011 VL 62 IS 9 BP 1001 EP 1003 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 814QK UT WOS:000294471800002 PM 21885575 ER PT J AU Li, HK Esquivel, A Hubbard, LD Florez-Arango, JF Danis, RP Krupinski, EA AF Li, Helen K. Esquivel, Adol Hubbard, Larry D. Florez-Arango, Jose F. Danis, Ronald P. Krupinski, Elizabeth A. TI MOSAICS VERSUS EARLY TREATMENT DIABETIC RETINOPATHY SEVEN STANDARD FIELDS FOR EVALUATION OF DIABETIC RETINOPATHY SEVERITY SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE classification; diabetic retinopathy; digital; film; fundus photography; mosaic wide angle; seven standard fields; reproducibility; telemedicine ID FUNDUS PHOTOGRAPHY; RETINAL IMAGES; FOLLOW-UP; GLAUCOMA; SYSTEM; TELEOPHTHALMOLOGY; EPIDEMIOLOGY; TELEMEDICINE; POPULATION; RISK AB Purpose: To compare agreement between mosaicked and seven field photographs for classification of the diabetic retinopathy (DR) severity. Methods: Mosaic digital (MosD) images were compared with seven field stereo film (7FF) and stereo digital (7FD) photographs from a 152-eye cohort with full-spectrum Early Treatment of Diabetic Retinopathy severity levels for agreement on severity level, DR presence with ascending severity thresholds, DR index lesion presence, and classification repeatability. Results: There was a substantial agreement classifying the Early Treatment Diabetic Retinopathy Study DR severity level between MosD and 7FF (k(unweighted) = 0.59, k(linear weighted) = 0.83), MosD and 7FD (kappa = 0.62, kappa (weighted) = 0.86), and 7FD and 7FF (kappa = 0.62, kappa (weighted) = 0.86) images. Marginal homogeneity analyses found no significant difference between MosD and 7FF (P = 0.44, Bhapkar's test). Kappa between MosD and 7FF ranged from 0.75 to 0.91 for the presence or absence of DR at 8 ascending severity thresholds. Repeatability among readers using MosD images was similar to repeatability among those using 7FF or 7FD. Repeatability among readers using MosD and 7FF images at various severity thresholds was similar. Kappa between MosD and 7FF grading for identifying DR lesions ranged from 0.61 to 1.00. Conclusion: Mosaic images are generally comparable with standard seven-field photographs for classifying DR severity. RETINA 31:1553-1563, 2011 C1 [Li, Helen K.] Thomas Jefferson Univ, Dept Ophthalmol, Philadelphia, PA 19107 USA. [Florez-Arango, Jose F.] Univ Texas Hlth Sci Ctr, Sch Biomed Sci, Houston, TX USA. [Esquivel, Adol] Houston Vet Affairs Med Ctr, Houston, TX USA. [Esquivel, Adol] Baylor Coll Med, Houston, TX 77030 USA. [Hubbard, Larry D.; Danis, Ronald P.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Florez-Arango, Jose F.] Univ De Antioquia, Medellin, Colombia. [Krupinski, Elizabeth A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. RP Li, HK (reprint author), 1400 Hermann Dr, Houston, TX 77004 USA. EM hlimed@mac.com OI Florez-Arango, Jose F/0000-0001-9083-0195 FU Juvenile Diabetes Foundation Research International, New York, NY; Research to Prevent Blindness (Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch); Research to Prevent Blindness (Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health FX This study was supported by a grant from Juvenile Diabetes Foundation Research International, New York, NY (HKL) and by unrestricted grants from the Research to Prevent Blindness (Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch and the Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health). NR 34 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD SEP PY 2011 VL 31 IS 8 BP 1553 EP 1563 DI 10.1097/IAE.0b013e3182084273 PG 11 WC Ophthalmology SC Ophthalmology GA 814LS UT WOS:000294456100014 PM 21522039 ER PT J AU MacMahon, PJ Murphy, DT Zoga, AC Kavanagh, EC AF MacMahon, Peter J. Murphy, Darra T. Zoga, Adam C. Kavanagh, Eoin C. TI Postoperative Imaging of the Elbow, Wrist, and Hand SO SEMINARS IN MUSCULOSKELETAL RADIOLOGY LA English DT Article DE Elbow; wrist; hand; postoperative ID ULNAR COLLATERAL LIGAMENT; CUBITAL TUNNEL-SYNDROME; POSTEROLATERAL ROTATORY INSTABILITY; REGIONAL BLOOD-FLOW; TERM FOLLOW-UP; SIMPLE DECOMPRESSION; OPERATIVE TREATMENT; MR ARTHROGRAPHY; BICEPS-BRACHII; NORMAL ANATOMY AB There are many bone and soft tissue injuries to the elbow, wrist, and hand that are treated surgically. The operative techniques can be complicated and their indications may change. This article reviews the common injuries at the elbow, wrist, and hand, the indications for surgical management, the current and previous operative techniques used, the expected postoperative appearance on different imaging modalities, and the important potential complications of each technique. C1 [MacMahon, Peter J.; Murphy, Darra T.; Kavanagh, Eoin C.] Mater Misericordiae Univ Hosp, Dept Radiol, Dublin, Ireland. [Zoga, Adam C.] Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA. RP MacMahon, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM petermacmahon@yahoo.com RI Murphy, Darra/B-7037-2013 OI Murphy, Darra/0000-0002-0266-7883 NR 93 TC 0 Z9 0 U1 0 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1089-7860 J9 SEMIN MUSCULOSKEL R JI Semin. Musculoskelet. Radiol. PD SEP PY 2011 VL 15 IS 4 BP 340 EP 356 DI 10.1055/s-0031-1286015 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 817DC UT WOS:000294650200004 PM 21928158 ER PT J AU Smedbakken, L Jensen, JK Hallen, J Atar, D Januzzi, JL Halvorsen, B Aukrust, P Ueland, T AF Smedbakken, Linda Jensen, Jesper K. Hallen, Jonas Atar, Dan Januzzi, James L. Halvorsen, Bente Aukrust, Pal Ueland, Thor TI Activated Leukocyte Cell Adhesion Molecule and Prognosis in Acute Ischemic Stroke SO STROKE LA English DT Article DE acute ischemic stroke; ALCAM; long-term prognosis ID INFLAMMATORY MECHANISMS; E-SELECTIN; PROLIFERATION; PREDICTION; ENGAGEMENT; INFECTION; RELEVANCE; TRIAL; CD6 AB Background and Purpose-Biomarkers predicting mortality and functional outcome in stroke may be clinically helpful in identification of patients likely to benefit from intervention. Activated leukocyte cell adhesion molecule (ALCAM) is upregulated during neuroinflammation; we investigated whether ALCAM concentrations are associated with long-term mortality after ischemic stroke. Methods-In 244 patients with acute ischemic stroke (age 69 +/- 13 years), samples of ALCAM were obtained serially from presentation to Day 5 and after 6 months. Patients with overt ischemic heart disease and atrial fibrillation were excluded. The patients were followed for 47 months with all-cause and cardiovascular mortality as end points. Results-At follow-up, 72 patients (29%) had died, 43 due to cardiovascular causes. Patients with ALCAM in the fourth quartile (>46.8 ng/mL) at admission had a significantly poorer survival rate on univariate analysis (P<0.001); other time points did not add further but provided similar prognostic information. In multivariate analysis, after adjustment for age, stroke severity, C-reactive protein levels, troponin T levels, and heart and/or renal failure, ALCAM levels above the fourth quartile remained an independent predictor of long-term mortality (adjusted hazard ratio, 2.05; 95% CI, 1.11 to 3.76; P=0.021) and cardiovascular mortality (adjusted hazard ratio, 2.54; 95% CI, 1.06 to 6.07; P=0.028). Conclusions-ALCAM levels measured at admission of acute ischemic stroke are associated with long-term mortality. (Stroke. 2011;42:2453-2458.) C1 [Smedbakken, Linda; Halvorsen, Bente; Aukrust, Pal; Ueland, Thor] Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, Oslo, Norway. [Aukrust, Pal] Oslo Univ Hosp, Rikshosp, Sect Clin Immunol & Infect Dis, Oslo, Norway. [Hallen, Jonas; Atar, Dan] Univ Oslo, Aker Hosp, Div Cardiol, Oslo, Norway. [Atar, Dan; Halvorsen, Bente; Aukrust, Pal; Ueland, Thor] Univ Oslo, Fac Med, Oslo, Norway. [Jensen, Jesper K.] Odense Univ Hosp, Dept Cardiol, DK-5000 Odense, Denmark. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Ueland, T (reprint author), Natl Hosp Norway, Res Inst Internal, Room D1-2017,Sognsvannsveien 20, N-0027 Oslo, Norway. EM thor.ueland@medisin.uio.no NR 28 TC 13 Z9 13 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD SEP PY 2011 VL 42 IS 9 BP 2453 EP 2458 DI 10.1161/STROKEAHA.110.612440 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 813BX UT WOS:000294342800026 PM 21757661 ER PT J AU Biffi, A Cortellini, L Nearnberg, CM Ayres, AM Schwab, K Gilson, AJ Rost, NS Goldstein, JN Viswanathan, A Greenberg, SM Rosand, J AF Biffi, Alessandro Cortellini, Lynelle Nearnberg, Caryn M. Ayres, Alison M. Schwab, Kristin Gilson, Aaron J. Rost, Natalia S. Goldstein, Joshua N. Viswanathan, Anand Greenberg, Steven M. Rosand, Jonathan TI Body Mass Index and Etiology of Intracerebral Hemorrhage SO STROKE LA English DT Article DE amyloid angiopathy; body mass index; epidemiology; etiology; hemorrhage; ICH; intracerebral hemorrhage; intracerebral hypertension; pathology ID AMYLOID ANGIOPATHY; PHYSICAL-ACTIVITY; RISK; STROKE; MEN; DISEASES AB Background and Purpose-Extremes of body mass index (BMI) are associated with increased incidence of intracerebral hemorrhage (ICH). Because ICH can result from different vessel pathologies, we investigated whether the effect of BMI depends on ICH etiology. Methods-We analyzed 384 consecutive ICH cases (188 lobar ICH and 196 deep ICH) and 388 control subjects enrolled between 2004 and 2009 in an ongoing single-center prospective study of primary ICH. ICH was categorized as lobar or deep based on CT imaging at admission. BMI was calculated based on subjects' height and weight at enrollment. We constructed multivariate logistic regression models including BMI and known predictors of ICH occurrence. Analyses were performed separately for lobar and deep ICH subjects versus control subjects. Results-Low BMI (<18.5 kg/m(2)) and very high BMI (>30.0 kg/m(2)) were associated with deep ICH risk (OR, 1.76; P=0.011 and OR, 1.75; P=0.013, respectively), whereas no effect was found for lobar ICH. Furthermore, sex-stratified analyses uncovered that among low BMI individuals, males were at higher ICH risk (OR, 2.85; P=0.041) but females were not (OR, 0.89; P=0.54, respectively). Conclusions-Extremes of BMI are associated with increased risk of deep ICH, but not lobar ICH, suggesting a role for BMI in the vascular pathologies underlying deep ICH, but not in pathologies such as cerebral amyloid angiopathy that cause ICH in the lobar brain regions. (Stroke. 2011;42:2526-2530.) C1 [Biffi, Alessandro; Cortellini, Lynelle; Nearnberg, Caryn M.; Rost, Natalia S.; Viswanathan, Anand; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA. [Biffi, Alessandro; Cortellini, Lynelle; Nearnberg, Caryn M.; Ayres, Alison M.; Schwab, Kristin; Gilson, Aaron J.; Rost, Natalia S.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Biffi, Alessandro; Cortellini, Lynelle; Nearnberg, Caryn M.; Rost, Natalia S.; Viswanathan, Anand; Rosand, Jonathan] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM jrosand@partners.org RI Goldstein, Joshua/H-8953-2016; OI Ayres, Alison/0000-0002-5492-1695 FU National Institute for Neurologic Disorders and Stroke [R01 NS063925, R01 NS059727, P50 NS051343, K23 NS064052, K23 NS059774]; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775011N, 0755984T] FX The authors' work on this study was supported by funding from the National Institute for Neurologic Disorders and Stroke (R01 NS063925, R01 NS059727, P50 NS051343, K23 NS064052, K23 NS059774). A. B. received support from the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775011N, 0755984T). All funding entities had no involvement in study design, data collection, analysis, interpretation, writing of the report, or in the decision to submit the article for publication. NR 16 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2011 VL 42 IS 9 BP 2526 EP 2530 DI 10.1161/STROKEAHA.111.617225 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 813BX UT WOS:000294342800038 PM 21778442 ER PT J AU Ren, XF Akiyoshi, K Vandenbark, AA Hurn, PD Offner, H AF Ren, Xuefang Akiyoshi, Kozaburo Vandenbark, Arthur A. Hurn, Patricia D. Offner, Halina TI Programmed Death-1 Pathway Limits Central Nervous System Inflammation and Neurologic Deficits in Murine Experimental Stroke SO STROKE LA English DT Article DE coinhibitory pathway; inflammatory cells; MCAO; programmed death-1 ID REGULATORY T-CELLS; PD-1; AUTOIMMUNITY; ACTIVATION; EXPRESSION; INFECTION; RESPONSES; CNS; MACROPHAGES; LIGANDS AB Background and Purpose-Evaluation of infarct volumes and infiltrating immune cell populations in mice after middle cerebral artery occlusion strongly implicates a mixture of both pathogenic and regulatory immune cell subsets that affect stroke outcome. Our goal was to evaluate the contribution of the well-described coinhibitory pathway, programmed death (PD)-1, to the development of middle cerebral artery occlusion. Methods-Infarct volumes, functional outcomes, and effects on infiltrating immune cell populations were compared in wild-type C57BL/6 versus PD-1-deficient mice after 60 minutes middle cerebral artery occlusion and 96 hours reperfusion. Results-The results clearly demonstrate a previously unrecognized activity of the PD-1 pathway to limit infarct volume, recruitment of inflammatory cells from the periphery, activation of macrophages and central nervous system microglia, and functional neurological deficits. These regulatory functions were associated with increased percentages of circulating PD-ligand-1 and PD-ligand-2 expressing CD19(+) B-cells in blood, the spleen, and central nervous system with the capacity to inhibit activation of inflammatory T-cells and central nervous system macrophages and microglial cells through upregulated PD-1. Conclusions-Our novel observations are the first to implicate PD-1 signaling as a major protective pathway for limiting central nervous system inflammation in middle cerebral artery occlusion. This inhibitory circuit would likely be pivotal in reducing stroke-associated Toll-like receptor-2- and Toll like receptor-4-mediated release of neurotoxic factors by activated central nervous system microglia. (Stroke. 2011;42:2578-2583.) C1 [Ren, Xuefang; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, R&D 31, Portland, OR 97239 USA. [Ren, Xuefang; Akiyoshi, Kozaburo; Hurn, Patricia D.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, 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 National Institutes of Health [NR03521, NS49210]; Biomedical Laboratory R&D Service, Department of Veterans Affairs FX This work was supported by National Institutes of Health grants NR03521 and NS49210 and the Biomedical Laboratory R&D Service, Department of Veterans Affairs. NR 33 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2011 VL 42 IS 9 BP 2578 EP U329 DI 10.1161/STROKEAHA.111.613182 PG 12 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 813BX UT WOS:000294342800046 PM 21737801 ER PT J AU Wagner, TH Lo, AC Peduzzi, P Bravata, DM Huang, GD Krebs, HI Ringer, RJ Federman, DG Richards, LG Haselkorn, JK Wittenberg, GF Volpe, BT Bever, CT Duncan, PW Siroka, A Guarino, PD AF Wagner, Todd H. Lo, Albert C. Peduzzi, Peter Bravata, Dawn M. Huang, Grant D. Krebs, Hermano I. Ringer, Robert J. Federman, Daniel G. Richards, Lorie G. Haselkorn, Jodie K. Wittenberg, George F. Volpe, Bruce T. Bever, Christopher T. Duncan, Pamela W. Siroka, Andrew Guarino, Peter D. TI An Economic Analysis of Robot-Assisted Therapy for Long-Term Upper-Limb Impairment After Stroke SO STROKE LA English DT Article DE cost; economic; rehabilitation; robotics; stroke ID AVERAGE COST; REHABILITATION; VA; HEALTH; STAYS AB Background and Purpose-Stroke is a leading cause of disability. Rehabilitation robotics have been developed to aid in recovery after a stroke. This study determined the additional cost of robot-assisted therapy and tested its cost-effectiveness. Methods-We estimated the intervention costs and tracked participants' healthcare costs. We collected quality of life using the Stroke Impact Scale and the Health Utilities Index. We analyzed the cost data at 36 weeks postrandomization using multivariate regression models controlling for site, presence of a prior stroke, and Veterans Affairs costs in the year before randomization. Results-A total of 127 participants were randomized to usual care plus robot therapy (n = 49), usual care plus intensive comparison therapy (n = 50), or usual care alone (n = 28). The average cost of delivering robot therapy and intensive comparison therapy was $5152 and $7382, respectively (P<0.001), and both were significantly more expensive than usual care alone (no additional intervention costs). At 36 weeks postrandomization, the total costs were comparable for the 3 groups ($17 831 for robot therapy, $19 746 for intensive comparison therapy, and $19 098 for usual care). Changes in quality of life were modest and not statistically different. Conclusions-The added cost of delivering robot or intensive comparison therapy was recuperated by lower healthcare use costs compared with those in the usual care group. However, uncertainty remains about the cost-effectiveness of robotic-assisted rehabilitation compared with traditional rehabilitation. Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique identifier: NCT00372411. (Stroke. 2011;42:2630-2632.) C1 [Wagner, Todd H.] Stanford Univ, VA Palo Alto Hlth Econ Resource Ctr, Menlo Pk, CA 94025 USA. [Wagner, Todd H.] Stanford Univ, Dept Hlth Res & Policy, Menlo Pk, CA 94025 USA. [Lo, Albert C.] Brown Univ, Providence Vet Adm Med Ctr, Neurol Sect, Providence, RI 02912 USA. Brown Univ, Dept Neurol, Providence, RI 02912 USA. Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. Brown Univ, Dept Engn, Providence, RI 02912 USA. [Peduzzi, Peter] Yale Univ, Sch Publ Hlth, Vet Adm Connecticut Cooperat Studies Program Coor, New Haven, CT USA. [Bravata, Dawn M.] Indianapolis Vet Adm Med Ctr, Indianapolis, IN USA. [Bravata, Dawn M.] Indiana Univ Sch Med, Indianapolis, IN USA. [Huang, Grant D.] Vet Affairs Off Res & Dev, Cooperat Studies Program Cent Off, Washington, DC USA. [Krebs, Hermano I.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Ringer, Robert J.] Univ New Mexico, Vet Affairs Cooperat Studies Program Clin Res Pha, Albuquerque, NM 87131 USA. [Federman, Daniel G.] Vet Affairs Connecticut Healthcare Syst, Dept Med, West Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. [Richards, Lorie G.] Univ Florida, N Florida S Georgia Vet Hlth Syst, Gainesville, FL USA. [Richards, Lorie G.] Univ Florida, Occupat Therapy Dept, Gainesville, FL USA. [Haselkorn, Jodie K.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Wittenberg, George F.] Univ Maryland, Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. [Volpe, Bruce T.] Cornell Univ, Dept Neurol & Neurosci, Weill Med Coll, White Plains, NY USA. [Bever, Christopher T.] Vet Affairs Maryland Hlth Care Syst, Neurol Serv, Baltimore, MD USA. [Bever, Christopher T.] Vet Affairs Maryland Hlth Care Syst, Res Serv, Baltimore, MD USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Phys Therapy, Baltimore, MD 21201 USA. [Duncan, Pamela W.] Duke Univ, Dept Community & Family Med, Durham, NC USA. [Siroka, Andrew] Vet Affairs Palo Alto Hlth Econ Resource Ctr, Palo Alto, CA USA. [Guarino, Peter D.] Cooperat Studies Coordinating Ctr, West Haven, CT USA. RP Wagner, TH (reprint author), Stanford Univ, VA Palo Alto Hlth Econ Resource Ctr, 795 Willow Rd,152 MPD, Menlo Pk, CA 94025 USA. EM Todd.Wagner@va.gov OI Volpe, Bruce/0000-0002-1098-1848 FU Department of Veterans Affairs; Rehabilitation Research and Development Service FX This study was funded by the Department of Veterans Affairs Cooperative Studies Program and the Rehabilitation Research and Development Service. NR 24 TC 39 Z9 44 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2011 VL 42 IS 9 BP 2630 EP U422 DI 10.1161/STROKEAHA.110.606442 PG 20 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 813BX UT WOS:000294342800056 PM 21757677 ER PT J AU Albers, GW Goldstein, LB Hess, DC Wechsler, LR Furie, KL Gorelick, PB Hurn, P Liebeskind, DS Nogueira, RG Saver, JL AF Albers, Gregory W. Goldstein, Larry B. Hess, David C. Wechsler, Lawrence R. Furie, Karen L. Gorelick, Philip B. Hurn, Patty Liebeskind, David S. Nogueira, Raul G. Saver, Jeffrey L. CA STAIR VII Consortium TI Stroke Treatment Academic Industry Roundtable (STAIR) Recommendations for Maximizing the Use of Intravenous Thrombolytics and Expanding Treatment Options With Intra-arterial and Neuroprotective Therapies SO STROKE LA English DT Article DE acute stroke; basic science; drug trials; neuroprotection; thrombolysis ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; TRIAL; MILD; TIME; REVASCULARIZATION; ASSOCIATION; PENUMBRA; OUTCOMES; HYPOTHERMIA AB Background and Purpose-The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of acute and restorative stroke therapies. Summary of Review-At the STAIR VII recommendations for strategies to maximize the use of intravenous thrombolytics through targeting public education, and the refinement of current treatment exclusion criteria were proposed. Increased utilization of mechanical devices for intra-arterial recanalization can be achieved by obtaining more definitive evidence of efficacy in randomized clinical trials, identification of patient characteristics associated with treatment efficacy, optimization of technical approaches, clarification of effective time windows, and development of approaches to limit complications. Neuroprotective strategies remain viable; recommendations for further study of these agents include an emphasis on rapid administration, consideration of the systemic effects of ischemic stroke, prevention of complications associated with early reperfusion, a focus on agents with multiple mechanisms of action, and consideration of possible interactions between neuroprotective and thrombolytic therapies. Conclusions-Extending intravenous thrombolysis to a broader patient population, clarifying the risk and benefits of intra-arterial reperfusion therapies, and further development of neuroprotective therapies were the key recommendations from STAIR VII. (Stroke. 2011;42:2645-2650.) C1 [Albers, Gregory W.] Stanford Univ, Dept Neurol & Neurol Sci, Stanford Stroke Ctr, Palo Alto, CA 94304 USA. [Goldstein, Larry B.] Duke Univ, Med Ctr, Durham, NC USA. [Hess, David C.] Med Coll Georgia, Augusta, GA 30912 USA. [Wechsler, Lawrence R.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gorelick, Philip B.] Univ Illinois, Coll Med, Chicago, IL USA. [Hurn, Patty] Univ Texas Syst, Austin, TX USA. [Liebeskind, David S.; Saver, Jeffrey L.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Nogueira, Raul G.] Emory Univ, Sch Med, Atlanta, GA USA. RP Albers, GW (reprint author), Stanford Univ, Dept Neurol & Neurol Sci, Stanford Stroke Ctr, 780 Welch Rd,Suite 205, Palo Alto, CA 94304 USA. EM albers@stanford.edu OI Schneider, Armin/0000-0003-0296-0059; Saver, Jeffrey/0000-0001-9141-2251 FU NIH; Athersys; Lundbeck FX G.W.A. received a research grant from NIH, and serves as a Consultant/Advisory Board member for Lundbeck and Genentech. D.C.H. received a research grant from Athersys and Lundbeck; honoraria from Sanofi-Aventis; has ownership interest in Reach Health; and serves as a Consultant/Advisory Board member for Athersys. L.R.W. has ownership interest in Neuro Interventional Therapeutic; serves as a Consultant/Advisory Board member for Abbott Vascular, Lundbeck, and Ferrer; DSMB DIAS 3/4; Steering committee ACT 1; and Steering committee CLOSURE. P.B.G. received a research grant from Lundbeck; Speakers Bureau for Boehringer Ingelheim; served as an expert witness; and serves as a Consultant/Advisory Board member for Lundbeck. D.S.L. received a research grant from the NIH, and serves as a Consultant/Advisory Board member for Concentric and Co-Axia. R.G.N. serves on the Speakers Bureau for Concentric, EV3, and CoAxia, and serves as a Consultant/Advisory Board member for Concentric, EV3, and CoAxia. J.L.S. serves as a Consultant/Advisory Board for Ev3, CoAxia, Talecris, Mitsubishi, BrainsGate, and Ferrer. NR 41 TC 77 Z9 79 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2011 VL 42 IS 9 BP 2645 EP 2650 DI 10.1161/STROKEAHA.111.618850 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 813BX UT WOS:000294342800061 PM 21852620 ER PT J AU Barry, MJ Avins, AL Meleth, S AF Barry, Michael J. Avins, Andrew L. Meleth, Sreelatha CA Complementary Alternative Med Urol TI Performance of the American Urological Association Symptom Index With and Without an Additional Urge Incontinence Item SO UROLOGY LA English DT Article ID BENIGN PROSTATIC HYPERPLASIA; URINARY-TRACT SYMPTOMS; OVERACTIVE BLADDER; HEALTH-STATUS; IMPACT INDEX; MEN; SCORE; DISTINCTION; BOTHER; TRIAL AB OBJECTIVE To examine the value of adding an urge incontinence question to the American Urological Association Symptom Index (AUASI) among men in the Complementary and Alternative Medicine for Urological Symptoms (CAMUS) trial. METHODS The CAMUS study was a randomized trial of Saw palmetto fruit extract versus placebo among men aged >= 45 years with an AUASI score of >= 8 and <= 24. The baseline measurements included the AUASI, a question about urge incontinence (UI), the International Prostate Symptom Score quality of life question, and the Benign Prostatic Hyperplasia Impact Index. We correlated the items and scales and examined whether adding the UI question resulted in better prediction of disease-specific health status. RESULTS The mean age of the 369 men in the CAMUS trial was 61 years, and mean baseline AUASI score was 14.6. UI was reported infrequently; about 82% of the respondents answered the question "not at all" or "<1 time in 5." UI correlated significantly with all other AUASI items, except for weak stream; the strongest correlation was to urgency (R = 0.51, P < .0001). The correlation between the AUASI score and the AUASI + UI score was 0.98 (P < .0001). In a logistic regression analysis predicting the International Prostate Symptom Score quality of life score, adding UI to the AUASI slightly increased the discriminating ability (c statistic increased from 0.77 to 0.78, P < .0001). Similarly, in a linear regression analysis predicting the Benign Prostatic Hyperplasia Impact Index score, adding UI to the AUASI slightly increased the predictive ability (R(2) statistic increased from 0.22 to 0.26, P < .0001). CONCLUSION According to our analysis in the CAMUS trial population, the value of adding a UI question to the AUASI in terms of predicting bother seemed small at best. UROLOGY 78: 550-554, 2011. (C) 2011 Elsevier Inc. C1 [Barry, Michael J.] Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Kaiser Permanente, No Calif Div Res, Oakland, CA USA. Univ Calif San Francisco, Dept Med, Sch Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Sch Med, San Francisco, CA 94143 USA. Univ Alabama, Sch Med, Div Prevent Med, Birmingham, AL USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mbarry@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK63795, U01 DK63797, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63831, U01 DK63778, U01 DK63788]; National Center for Complementary and Alternative Medicine; Office of Dietary Supplements, National Institutes of Health FX The CAMUS trial was funded by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01 DK63795, U01 DK63797, U01 DK63835, U01 DK63866, U01 DK63833, U01 DK63862, U01 DK63840, U01 DK63833, U01 DK63831, U01 DK63778 and U01 DK63788) and by the National Center for Complementary and Alternative Medicine and the Office of Dietary Supplements, National Institutes of Health. NR 17 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD SEP PY 2011 VL 78 IS 3 BP 550 EP 554 DI 10.1016/j.urology.2011.04.017 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 814US UT WOS:000294483300024 PM 21741692 ER PT J AU Stovsky, M Ponsky, L Vourganti, S Stuhldreher, P Siroky, MB Kipnis, V Fedotoff, O Mikheeva, L Zaslavsky, B Chait, A Jones, JS AF Stovsky, Mark Ponsky, Lee Vourganti, Srinivas Stuhldreher, Peter Siroky, Mike B. Kipnis, Victor Fedotoff, Olga Mikheeva, Larissa Zaslavsky, Boris Chait, Arnon Jones, J. Stephen TI Prostate-specific Antigen/Solvent Interaction Analysis: A Preliminary Evaluation of a New Assay Concept for Detecting Prostate Cancer Using Urinary Samples SO UROLOGY LA English DT Article ID ANTIGEN; SERUM; LECTIN; PSA; GLYCOSYLATION; PATTERNS; BINDING; LEVEL; MEN AB OBJECTIVE To provide preliminary clinical performance evaluation of a novel prostate cancer (CaP) assay, prostate-specific antigen/solvent interaction analysis (PSA/SIA) that focused on changes to the structure of PSA. METHODS Two-hundred twenty-two men undergoing prostate biopsy for accepted clinical criteria at 3 sites (University Hospitals Case Medical Center in Cleveland, Cleveland Clinic, and Veterans Administration Boston Healthcare System) were enrolled in institutional review board-approved study. Before transrectal ultrasound-guided biopsy, patients received digital rectal examination with systematic prostate massage followed by collection of urine. The PSA/SIA assay determined the relative partitioning of heterogeneous PSA isoform populations in urine between 2 aqueous phases. A structural index, K, whose numerical value is defined as the ratio of the concentration of all PSA isoforms, was determined by total PSA enzyme-linked immunosorbent assay and used to set a diagnostic threshold for CaP. Performance was assessed using receiver operating characteristic (ROC) analysis with biopsy as the gold standard. RESULTS Biopsies were pathologically classified as case (malignant, n = 100) or control (benign, n = 122). ROC performance demonstrated area under the curve = 0.90 for PSA/SIA and 0.58 for serum total PSA. At a cutoff value of k = 1.73, PSA/SIA displayed sensitivity = 100%, specificity = 80.3%, positive predictive value = 80.6%, and negative predictive value = 100%. No attempt was made in this preliminary study to further control patient population or selection criteria for biopsy, nor did we analytically investigate the type of structural differences in PSA that led to changes in k value. CONCLUSION PSA/SIA provides ratiometric information independently of PSA concentration. In this preliminary study, analysis of the overall structurally heterogeneous PSA isoform population using the SIA assay showed promising results to be further evaluated in future studies. UROLOGY 78: 601-606, 2011. (C) 2011 Elsevier Inc. All rights reserved. C1 [Stovsky, Mark] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Urol, Cleveland, OH 44106 USA. Boston Healthcare Syst, Vet Adm, Boston, MA USA. NCI, Bethesda, MD 20892 USA. AnalizaDx, Cleveland, OH USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Stovsky, M (reprint author), Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Urol, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM gowildgo@aol.com OI Zaslavsky, Boris/0000-0003-0771-6696 FU Intramural NIH HHS [Z99 CA999999] NR 23 TC 11 Z9 11 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD SEP PY 2011 VL 78 IS 3 BP 601 EP 605 DI 10.1016/j.urology.2011.03.071 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 814US UT WOS:000294483300041 PM 21783231 ER PT J AU Oh, WK Galsky, MD Stadler, WM Srinivas, S Chu, F Bubley, G Goddard, J Dunbar, J Ross, RW AF Oh, William K. Galsky, Matthew D. Stadler, Walter M. Srinivas, Sandy Chu, Franklin Bubley, Glenn Goddard, J. Dunbar, Joi Ross, Robert W. TI Multicenter Phase II Trial of the Heat Shock Protein 90 Inhibitor, Retaspimycin Hydrochloride (IPI-504), in Patients With Castration-resistant Prostate Cancer SO UROLOGY LA English DT Article ID ANDROGEN RECEPTOR; HSP90 INHIBITORS; ANTICANCER AGENT; CLINICAL-TRIALS; TUMOR-GROWTH; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; HEAT-SHOCK-PROTEIN-90; HYDROQUINONE; NSC-330507; HER-2/NEU AB OBJECTIVE To evaluate clinical activity and safety of retaspimycin hydrochloride (IPI-504) in patients with castration-resistant prostate cancer (CRPC). METHODS A single-arm trial was conducted in 2 cohorts: group 1, chemotherapy naive; group 2, docetaxel-treated. IPI-504 was administered intravenously at 400 mg/m(2) on days 1, 4, 8, and 11 of a 21-day cycle. Trial expansion was planned if >= 1 prostate-specific antigen (PSA) or radiographic response was noted per cohort. Pharmacokinetic samples were collected after the first dose; safety was assessed throughout. RESULTS A total of 19 patients were enrolled (4 in group 1; 15 in group 2), with a median age of 66 years (range 49-78). Group 2 had received a median of 2 previous chemotherapy regimens. All group 2 patients had bone metastases; 66% had measurable soft tissue or visceral metastases. One group 1 patient remained on-trial for 9 cycles; his PSA level declined 48% from baseline. No PSA response was observed in the other patients. Adverse events reported in >25% of the study population included nausea (47%), diarrhea (42%), fatigue (32%), anorexia (26%), and arthralgia (26%). Two patients in group 2 died on-trial, involving study drug-related events of hepatic failure and ketoacidosis, respectively. CONCLUSION Heat shock protein 90 inhibition with IPI-504 administered as a single agent had a minimal effect on the PSA level or tumor burden and was associated with unacceptable toxicity in several patients. Therefore, additional evaluation in CRPC patients is not warranted. IPI-504 is being investigated at less-intensive doses and schedules in other tumor types. UROLOGY 78: 626-630, 2011. (C) 2011 Elsevier Inc. C1 Mt Sinai Sch Med, New York, NY USA. Univ Chicago, Chicago, IL 60637 USA. Stanford Univ, Stanford, CA 94305 USA. San Bernardino Urol, San Bernardino, CA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Infin Pharmaceut Inc, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Oh, WK (reprint author), Mt Sinai Med Ctr, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM william.oh@mssm.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU NCI NIH HHS [R21 CA128352, R21 CA128352-01A1, R21 CA128352-02] NR 28 TC 37 Z9 37 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD SEP PY 2011 VL 78 IS 3 BP 626 EP 630 DI 10.1016/j.urology.2011.04.041 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 814US UT WOS:000294483300049 PM 21762967 ER PT J AU Huddle, TS AF Huddle, Thomas S. TI Do Medical Professionalism and Medical Education Involve Commitments to Political Advocacy? Reply SO ACADEMIC MEDICINE LA English DT Letter C1 [Huddle, Thomas S.] Univ Alabama, Dept Med, Div Gen Internal Med, Med Sch Birmingham, Birmingham, AL 35294 USA. [Huddle, Thomas S.] Birmingham VA Med Ctr, Birmingham, AL USA. RP Huddle, TS (reprint author), Univ Alabama, Dept Med, Div Gen Internal Med, Med Sch Birmingham, Birmingham, AL 35294 USA. EM thuddle@uab.edu RI liu, jing/D-9482-2012 NR 0 TC 3 Z9 3 U1 0 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 SEP PY 2011 VL 86 IS 9 BP 1065 EP 1065 DI 10.1097/ACM.0b013e3182277361 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 811YH UT WOS:000294254300010 ER PT J AU Slavin, PL AF Slavin, Peter L. TI Commentary: Health Care Reform and the Finances of Academic Medical Centers SO ACADEMIC MEDICINE LA English DT Editorial Material AB Academic medical centers (AMCs; i.e., teaching hospitals) play a vital role in the U. S. health care system by pursuing a four-part, synergistic mission of clinical care, research, education, and community health. Historically, AMCs have used margins from clinical care to subsidize the cost of the other three missions. As a result, the clinical cost structure of AMCs is higher than other hospitals. The study by McCue and Thompson in this issue of Academic Medicine identifies certain factors (such as Medicaid payer mix) that are associated with the financial success of AMCs. For national health care reform to be successful and for health care to be affordable, all providers across the United States, including AMCs, must aggressively identify and implement opportunities to make care better and more efficient. Policies that shape national health care reform must account for AMCs' higher cost structures. If policy makers ignore these higher cost structures, the ability of AMCs to provide highly specialized services, to care for vulnerable populations, to advance knowledge through biomedical research, to educate the next generation of health professionals, and to improve community health will be at risk. C1 [Slavin, Peter L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Slavin, Peter L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Slavin, PL (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM pslavin@partners.org NR 6 TC 4 Z9 4 U1 0 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 SEP PY 2011 VL 86 IS 9 BP 1076 EP 1078 DI 10.1097/ACM.0b013e3182267c1d PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 811YH UT WOS:000294254300015 PM 21865905 ER PT J AU Ackerly, DC Udayakumar, K Taber, R Merson, MH Dzau, VJ AF Ackerly, D. Clay Udayakumar, Krishna Taber, Robert Merson, Michael H. Dzau, Victor J. TI Perspective: Global Medicine: Opportunities and Challenges for Academic Health Science Systems SO ACADEMIC MEDICINE LA English DT Article ID GLOBALIZATION; INNOVATION; HOSPITALS; CENTERS; CARE AB Globalization is having a growing impact on health and health care, presenting challenges as well as opportunities for the U. S. health care industry in general and for academic health science systems (AHSSs) in particular. The authors believe that AHSSs must develop long-term strategies that address their future role in global medicine. AHSSs should meet global challenges through planning, engagement, and innovation that combine traditional academic activities with entrepreneurial approaches to health care delivery, research, and education, including international public-private partnerships. The opportunities for U. S.-based AHSSs to be global health care leaders and establish partnerships that improve health locally and globally more than offset the potential financial, organizational, politico-legal, and reputational risks that exist in the global health care arena. By examining recent international activities of leading AHSSs, the authors review the risks and the critical factors for success and discuss external policy shifts in workforce development and accreditation that would further support the growth of global medicine. C1 [Dzau, Victor J.] Duke Univ, Sch Med, Med Ctr, Durham, NC 27710 USA. [Dzau, Victor J.] Duke Univ Hlth Syst, Durham, NC USA. [Udayakumar, Krishna] Duke Univ, Med Ctr, Duke Med Initiat Hlth Innovat, Durham, NC 27710 USA. [Ackerly, D. Clay] Duke Univ, Duke Clin Res Inst, Durham, NC 27710 USA. [Ackerly, D. Clay] Harvard Univ, Sch Med, Boston, MA USA. [Ackerly, D. Clay] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Udayakumar, Krishna] Duke Med Global, Durham, NC USA. [Udayakumar, Krishna] Duke NUS Grad Med Sch, Singapore, Singapore. [Merson, Michael H.] Duke Global Hlth Inst, Durham, NC USA. RP Dzau, VJ (reprint author), Duke Univ, Sch Med, Med Ctr, Box 3701, Durham, NC 27710 USA. EM victor.dzau@duke.edu FU Duke Endowment FX Supported by a grant from the Duke Endowment. NR 47 TC 15 Z9 16 U1 0 U2 12 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 SEP PY 2011 VL 86 IS 9 BP 1093 EP 1099 DI 10.1097/ACM.0b013e318226b455 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 811YH UT WOS:000294254300018 PM 21785305 ER PT J AU Becher, A El-Serag, H AF Becher, A. El-Serag, H. TI Systematic review: the association between symptomatic response to proton pump inhibitors and health-related quality of life in patients with gastro-oesophageal reflux disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID MAINTENANCE TREATMENT; PRIMARY-CARE; ESOMEPRAZOLE; RABEPRAZOLE; HEARTBURN; GERD AB Background Some patients with gastro-oesophageal reflux disease (GERD) experience persistent reflux symptoms on proton pump inhibitor (PPI) therapy. The relationship between persistent reflux symptoms and health-related quality of life (HRQoL) is unclear. Aim To assess the relationship between persistent reflux symptoms on PPI therapy and HRQoL in patients with GERD. Methods Systematic searches were conducted in PubMed and Embase. Eligible studies had to have used psychometrically evaluated patient reported outcome instruments to assess HRQoL. Results Nine studies were included; supplementary data were obtained for four of these. The effect of persistent reflux symptoms despite PPI therapy on physical HRQoL was assessed in seven studies and that on mental HRQoL in five studies. Compared with patients whose reflux symptoms responded to PPIs, those with persistent symptoms had, on average, 8-16% lower scores for physical health (five studies) and 2-12% lower scores for mental health (three studies). Three studies included data on the effect of baseline HRQoL on subsequent symptomatic response to PPI therapy. Patients with persistent symptoms had clinically relevant lower psychological well-being at baseline compared with those whose symptoms responded to PPIs (average score difference: 7%; two studies). High anxiety levels at baseline seemed to be an important aspect of persistent symptoms. Conclusions Persistent reflux symptoms on PPI therapy are associated with reduced physical and mental HRQoL, while reduced mental HRQoL at baseline seems to impair symptomatic response to PPIs. HRQoL may need to be considered alongside reflux symptom frequency and severity when making decisions about disease management. C1 [Becher, A.] Oxford PharmaGenesis Ltd, Res Evaluat Unit, Oxford, England. [El-Serag, H.] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. [El-Serag, H.] Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, H (reprint author), Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU Bayer pharmaceuticals; Houston VA HSR&D Center of Excellence [HFP90-020]; AstraZeneca; AstraZeneca R&D, Molndal, Sweden FX Declaration of personal interests: Dr El-Serag has served as a consultant for Vertex, has received a grant from Bayer pharmaceuticals, and has received research funding from the Houston VA HSR&D Center of Excellence (HFP90-020). Dr Becher is a contracted employee of Oxford PharmaGenesis (TM) Ltd, which receives funding from AstraZeneca. Declaration of funding interests: Writing support was provided by Dr Lucy Bomphrey of Oxford PharmaGenesis (TM) Ltd and funded by AstraZeneca R&D, Molndal, Sweden. NR 22 TC 36 Z9 40 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD SEP PY 2011 VL 34 IS 6 BP 618 EP 627 DI 10.1111/j.1365-2036.2011.04774.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 810EE UT WOS:000294107400003 PM 21770991 ER PT J AU Saenz, AJ Johnson, NV Van Cott, EM AF Saenz, Adam J. Johnson, Nicholas V. Van Cott, Elizabeth M. TI Acquired Activated Protein C Resistance Caused by Lupus Anticoagulants SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Acquired activated protein C resistance; Lupus anticoagulant; Venous thrombosis ID FACTOR-V-LEIDEN; ANTIPHOSPHOLIPID SYNDROME; UPDATE; THROMBOSIS; CRITERIA; STROKE; RISK AB Lupus anticoagulants (LA) can cause acquired activated protein C resistance (APC-R), but the clinical significance is unclear. To investigate thrombosis and acquired APC-R in patients with LA, we enrolled all 132 patients undergoing hypercoagulability testing with positive LA results and in whom APC-R (with factor V deficient plasma) was performed during a 2.5-year period. Among 121 patients without factor V Leiden, 24.0% had acquired APC-R; retrospective and prospective (mean follow-up, 2.0 years) thrombotic events were analyzed. The distribution of venous vs arterial thrombosis was different for APC-R vs no APC-R (P = .0064). The majority (19/29 [66%]) with acquired APC-R experienced venous thrombosis, whereas a minority experienced arterial thrombosis (9/29 [31%]; P = .017). The opposite pattern occurred among patients without APC-R (arterial thrombi more common than venous thrombi). After excluding thrombotic events more than 5 years from a positive LA test, venous thrombosis occurred in 62% with (18/29) vs 32% without (29/92) APC-R (P = .0045); and arterial thrombosis in 28% with (8/29) vs 51% without (47/92) APC-R (P = .033). Patients with acquired APC-R due to LA had more venous thrombosis than did patients with LA without APC-R and experienced venous more often than arterial thrombosis. C1 [Saenz, Adam J.; Johnson, Nicholas V.; Van Cott, Elizabeth M.] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Gray Jackson 235,55 Fruit St, Boston, MA 02114 USA. NR 12 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2011 VL 136 IS 3 BP 344 EP 349 DI 10.1309/AJCP9OHZNZBHNXBE PG 6 WC Pathology SC Pathology GA 809SA UT WOS:000294075800001 PM 21846908 ER PT J AU Mahlen, SD Clarridge, JE AF Mahlen, Steven D. Clarridge, Jill E., III TI Evaluation of a Selection Strategy Before Use of 16S rRNA Gene Sequencing for the Identification of Clinically Significant Gram-Negative Rods and Coccobacilli SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE 16S rRNA gene sequencing; Gram-negative rod; Bacteria selection for sequence identification ID BACTERIAL IDENTIFICATION; MICROBIOLOGY; CARD AB Although 16S ribosomal RNA (rRNA) gene sequencing is well established for correctly identifying bacteria, its most efficient use in a routine clinical laboratory is not clear. We devised and evaluated a strategy to select gram-negative rods and coccobacilli (GNRCB) for which sequencing might be necessary before routine identification methods had been exhausted. The prospectively applied selection criteria were primarily based on the isolate's display of unusual or discordant phenotypic results and/or disease correlation. By using this strategy, we selected a total of 120 GNRCB (representing only similar to 2% of all identified). The strategy was demonstrated to be efficient because the preliminary phenotypic identification for 79.2% of those isolates needed revision (18.2% were novel and about a third would have required further extensive testing). The knowledge that 1.6% (ie, 79% of 2%) of isolated GNRCB might benefit from sequence identification could provide guidelines for routine clinical laboratories toward efficient use of sequence analysis. C1 [Mahlen, Steven D.; Clarridge, Jill E., III] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Clarridge, Jill E., III] Vet Affairs Puget Sound Hlth Care Syst, Pathol & Lab Med Serv, Seattle, WA USA. RP Clarridge, JE (reprint author), VA PSHCS, Pathol & Lab Med Serv 113, 1660 S Columbian Way, Seattle, WA 98108 USA. FU VA Puget Sound Health Care System FX This material is the result of work supported by resources from the VA Puget Sound Health Care System. NR 16 TC 6 Z9 7 U1 0 U2 4 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2011 VL 136 IS 3 BP 381 EP 388 DI 10.1309/AJCP61CGNXCXVSPR PG 8 WC Pathology SC Pathology GA 809SA UT WOS:000294075800006 PM 21846913 ER PT J AU Korte, JE Magruder, KM Chiuzan, CC Logan, SL Killeen, T Bandyopadhyay, D Brady, KT AF Korte, Jeffrey E. Magruder, Kathryn M. Chiuzan, Codruta C. Logan, Sarah L. Killeen, Therese Bandyopadhyay, Dipankar Brady, Kathleen T. TI Assessing Drug Use during Follow-Up: Direct Comparison of Candidate Outcome Definitions in Pooled Analyses of Addiction Treatment Studies SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE drug addiction; measurement; clinical trials; methodology ID ABUSE TREATMENT PROGRAMS; SELF-REPORT; ALCOHOL DEPENDENCE; CLINICAL-TRIALS; CONCORDANCE; REDUCTION; DRINKING AB Background: Selection of appropriate outcome measures is important for clinical studies of drug addiction treatment. Researchers use various methods for collecting drug use outcomes and must consider substances to be included in a urine drug screen (UDS); accuracy of self-report; use of various instruments and procedures for collecting self-reported drug use; and timing of outcome assessments. Objectives: We sought to define a set of candidate measures to (1) assess their intercorrelation and (2) identify any differences in results. Methods: Data were combined from completed protocols in the National Institute on Drug Abuse Clinical Trials Network (CTN), with a total of 1897 participants. We defined nine outcome measures based on UDS, self-report, or a combination. Multivariable, multilevel generalized estimating equation models were used to assess subgroup differences in intervention success, controlling for baseline differences and accounting for clustering by CTN protocols. Results: There were high correlations among all candidate outcomes. All outcomes showed consistent overall results with no significant intervention impact on drug use during follow-up. However, with most UDS variables, but not with self-report or "corrected self-report," we observed a significant gender-ethnicity interaction with benefit shown in African American women, White women, and Hispanic men. Conclusion: Despite strong associations between candidate measures, we found some important differences in results. Scientific Significance: In this study, we demonstrated the potential utility and impact of combining UDS and self-report data for drug use assessment. Our results suggest possible differences in intervention efficacy by gender and ethnicity, but highlight the need to cautiously interpret observed interactions. C1 [Korte, Jeffrey E.; Magruder, Kathryn M.; Chiuzan, Codruta C.; Logan, Sarah L.; Bandyopadhyay, Dipankar] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Magruder, Kathryn M.; Brady, Kathleen T.] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Div Behav Epidemiol & Community Hlth, Charleston, SC 29425 USA. [Killeen, Therese; Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Div Clin Neurosci, Charleston, SC 29425 USA. RP Korte, JE (reprint author), Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, 135 Cannon St,Suite 303, Charleston, SC 29425 USA. EM korte@musc.edu FU NIDA NIH HHS [5 U10 DA013727, U10 DA013727-10S1, U10 DA013727, U10 DA013727-11] NR 11 TC 3 Z9 3 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD SEP PY 2011 VL 37 IS 5 BP 358 EP 366 DI 10.3109/00952990.2011.602997 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 810HN UT WOS:000294116500012 PM 21854278 ER PT J AU Fickie, MR Lapunzina, P Gentile, JK Tolkoff-Rubin, N Kroshinsky, D Galan, E Gean, E Martorell, L Romanelli, V Toral, JF Lin, AE AF Fickie, Matthew R. Lapunzina, Pablo Gentile, Jennifer K. Tolkoff-Rubin, Nina Kroshinsky, Daniela Galan, Enrique Gean, Esther Martorell, Loreto Romanelli, Valeria Fernandez Toral, Joaquin Lin, Angela E. TI Adults With Sotos Syndrome: Review of 21 Adults With Molecularly Confirmed NSD1 Alterations, Including a Detailed Case Report of the Oldest Person SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Review DE adults with genetic disorders; familial gigantism; overgrowth syndrome; NSD1; Sotos syndrome; transitional care ID SYNDROME CEREBRAL GIGANTISM; DISORDER; PATIENT AB Sotos syndrome is a well-described multiple anomaly syndrome characterized by overgrowth, distinctive craniofacial appearance, and variable learning disabilities. The diagnosis of Sotos syndrome relied solely on these clinical criteria until haploin-sufficiency of the NSD1 gene was identified as causative. We describe a 63-year-old woman with classic features and a pathogenic NSD1 mutation, who we believe to be the oldest reported person with Sotos syndrome. She is notable for the diagnosis of Sotos syndrome late in life, mild cognitive limitation, and chronic kidney disease attributed to fibromuscular dysplasia for which she recently received a transplant. She has basal cell and squamous cell carcinoma for which her lifetime of sun exposure and fair cutaneous phototype are viewed as risk factors. We also reviewed previous literature reports (n = 11) for adults with Sotos syndrome, and studied patients ascertained in the Spanish Overgrowth Syndrome Registry (n = 15). Analysis was limited to 21/27 (78%) total patients who had molecular confirmation of Sotos syndrome (15 with a mutation, 6 with a microdeletion). With a mean age of 26 years, the most common features were learning disabilities (90%), scoliosis (52%), eye problems (43%), psychiatric issues (30%), and brain imaging anomalies (28%). Learning disabilities were more severe in patients with a microdeletion than in those with a point mutation. From this small study with heterogeneous ascertainment we suggest modest adjustments to the general healthcare monitoring of individuals with Sotos syndrome. Although this series includes neoplasia in four cases, this should not be interpreted as incidence. Age-appropriate cancer surveillance should be maintained. (C) 2011 Wiley-Liss, Inc. C1 [Fickie, Matthew R.; Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA. [Fickie, Matthew R.] Harvard Univ, Sch Med, Genet Training Program, Boston, MA USA. [Lapunzina, Pablo] Hosp Univ La Paz IdiPAZ, Inst Invest, INGMM, Madrid, Spain. [Lapunzina, Pablo] ISCIII, CIBERER, Madrid, Spain. [Lapunzina, Pablo] RESSC, Madrid, Spain. [Gentile, Jennifer K.] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Tolkoff-Rubin, Nina] Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. [Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Galan, Enrique] Hosp Materno Infatil Badajoz, Dept Pediat, Badajoz, Spain. [Gean, Esther] Hosp St Joan de Deu, Secc Genet Med, Barcelona, Spain. [Martorell, Loreto] Hosp St Joan de Deu, Secc Genet Mol, Barcelona, Spain. [Romanelli, Valeria] Hosp Univ La Paz, INGEMM, Madrid, Spain. [Fernandez Toral, Joaquin] Hosp Univ Cent Asturias, Secc Genet Pediat, Oviedo, Spain. RP Fickie, MR (reprint author), Baystate Childrens Hosp, Div Genet, 795 Chestnut St, Springfield, MA 01199 USA. EM matthew.fickie@baystatehealth.org NR 31 TC 12 Z9 13 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2011 VL 155A IS 9 BP 2105 EP 2111 DI 10.1002/ajmg.a.34156 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 811DN UT WOS:000294182500013 PM 21834047 ER PT J AU Caleshu, C Sakhuja, R Nussbaum, RL Schiller, NB Ursell, PC Eng, C De Marco, T McGlothlin, D Burchard, EG Rame, JE AF Caleshu, Colleen Sakhuja, Rahul Nussbaum, Robert L. Schiller, Nelson B. Ursell, Philip C. Eng, Celeste De Marco, Teresa McGlothlin, Dana Burchard, Esteban Gonzalez Rame, J. Eduardo TI Furthering the Link Between the Sarcomere and Primary Cardiomyopathies: Restrictive Cardiomyopathy Associated With Multiple Mutations in Genes Previously Associated With Hypertrophic or Dilated Cardiomyopathy SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE restrictive cardiomyopathy; hypertrophic cardiomyopathy; sarcomere; genetic testing; genetic counseling; cardiovascular genetics ID MYOSIN HEAVY-CHAIN; HEART-FAILURE; CLASSIFICATION; POPULATION; IDENTIFICATION; EPIDEMIOLOGY; PREVALENCE; CARDIOLOGY; PHYSIOLOGY; STATEMENT AB Mutations in genes that encode components of the sarcomere are well established as the cause of hypertrophic and dilated cardiomyopathies. Sarcomere genes, however, are increasingly being associated with other cardiomyopathies. One phenotype more recently recognized as a disease of the sarcomere is restrictive cardiomyopathy (RCM). We report on two patients with RCM associated with multiple mutations in sarcomere genes not previously associated with RCM. Patient 1 presented with NYHA Class III/IV heart failure at 22 years of age. She was diagnosed with RCM and advanced heart failure requiring heart transplantation. Sequencing of sarcomere genes revealed previously reported homozygous p.Glu143Lys mutations in MYL3, and a novel heterozygous p.Gly57Glu mutation in MYL2. The patient's mother is a double heterozygote for these mutations, with no evidence of cardiomyopathy. Patient 2 presented at 35 years of age with volume overload while hospitalized for oophorectomy. She was diagnosed with RCM and is being evaluated for heart transplantation. Sarcomere gene sequencing identified homozygous p.Asn279His mutations in TPM1. The patient's parents are consanguineous and confirmed heterozygotes. Her father was diagnosed with HCM at 42 years of age. This is the first report of mutations in TPM1, MYL3, and MYL2 associated with primary, non-hypertrophied RCM. The association of more sarcomere genes with RCM provides further evidence that mutations in the various sarcomere genes can cause different cardiomyopathy phenotypes. These cases also contribute to the growing body of evidence that multiple mutations have an additive effect on the severity of cardiomyopathies. (C) 2011 Wiley-Liss, Inc. C1 [Caleshu, Colleen] Stanford Univ, Med Ctr, Stanford Ctr Inherited Cardiovasc Dis, Stanford, CA 94305 USA. [Sakhuja, Rahul] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, Div Med Genet, San Francisco, CA USA. [Nussbaum, Robert L.; Burchard, Esteban Gonzalez] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Schiller, Nelson B.; De Marco, Teresa; McGlothlin, Dana] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA. [Ursell, Philip C.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Eng, Celeste; Burchard, Esteban Gonzalez] Univ Calif San Francisco, Lung Biol Ctr, Dept Med, San Francisco, CA 94143 USA. [Burchard, Esteban Gonzalez] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. [Rame, J. Eduardo] Univ Penn, Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. RP Caleshu, C (reprint author), Falk Cardiovasc Res Ctr, 300 Pasteur Dr, Stanford, CA 94305 USA. EM ccaleshu@stanfordmed.org FU Esteban Gonzalez Buronard [RO1 ESO15794]; NIH/NIEHS [RO1 HLO88133]; NIH/NHLBI [3/0108- 2/28/13]; NIH/NIAID [4/0108-3/31/13i, U19 A1O77439]; [9/01/8- 5/31/13] FX Grant sponsor: RO1 ESO15794; Pl: Esteban Gonzalez Buronard; Project Period: 9/01/8- 5/31/13; NIH/NIEHS; Grant sponsor: RO1 HLO88133; Pl: Esteban Gonzalez Buronard; Project Period: 3/0108- 2/28/13; NIH/NHLBI; Grant sponsor: U19 A1O77439; Pl: Dean Sheppard; Project Period: 4/0108-3/31/13i; NIH/NIAID. NR 33 TC 18 Z9 20 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD SEP PY 2011 VL 155A IS 9 BP 2229 EP 2235 DI 10.1002/ajmg.a.34097 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 811DN UT WOS:000294182500030 PM 21823217 ER PT J AU Ittiwut, R Listman, JB Ittiwut, C Cubells, JF Weiss, RD Brady, K Oslin, D Farrer, LA Kranzler, HR Gelernter, J AF Ittiwut, Rungnapa Listman, Jennifer B. Ittiwut, Chupong Cubells, Joseph F. Weiss, Roger D. Brady, Kathleen Oslin, David Farrer, Lindsay A. Kranzler, Henry R. Gelernter, Joel TI Association Between Polymorphisms in Catechol-O-methyltransferase (COMT) and Cocaine-Induced Paranoia in European-American and African-American Populations SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE COMT; cocaine-induced paranoia; family-based analysis; haplotype; SNP; positive selection ID 22Q11.2 DELETION SYNDROME; BETA-HYDROXYLASE ACTIVITY; GENOMEWIDE LINKAGE SCAN; HUMAN BRAIN; FUNCTIONAL POLYMORPHISM; GENETIC-VARIATION; MESSENGER-RNA; DBH LOCUS; HAPLOTYPE; DEPENDENCE AB Catechol-O-methyltransferase (genetic locus, COMT) is a major enzyme involved in catecholamine metabolism and has been associated with numerous psychiatric phenotypes. We studied COMT SNPs and haplotypes in cocaine-induced paranoia (CIP) in African-American (AA) and European-American (EA) populations. We genotyped 17 SNPs across the COMT locus in 319 AA pedigrees (848 individuals) and 302 EA pedigrees (707 individuals). Family-controlled association analyses were conducted using FBAT. We found SNP rs737865 to be nominally significantly associated in the AA family population (P = 0.05). In EAs, the best-known marker, rs4680 (Val158Met), was nominally significant in additive models (P = 0.03). SNP rs174696 also showed nominal significance in additive models (P = 0.02). We considered the three SNPs (rs737866-rs4680-rs174696) together in haplotype analysis in both family populations, using HBAT. The A-A-T haplotype was significantly associated with CIP in EAs (Z = 2.845; P = 0.0044, global P = 0.020). We then studied COMT SNPs in an additional 738 AA and 404 EA unrelated cocaine dependent individuals with and without paranoia. The A-A-T haplotype was significantly associated to CIP in the AA unrelated population (P = 0.0015). Two haplotypes, A-G-C and A-A-C, were significant in the EA unrelated population (P = 0.001 and 0.0003). We also identified rs4680 and three other SNPs, rs933271, rs5993883, and rs740603, as potentially functional variants, as predicted by a signature of positive selection in unrelated EAs and AAs. Based on our robust family-controlled and unrelated-affected analyses, we conclude that COMT is associated with CIP, possibly as a result of its role in the metabolism of dopamine and norepinephrine. (C) 2011 Wiley-Liss, Inc. C1 [Gelernter, Joel] Yale Univ Sch Med, VAMC 116A2, Dept Psychiat, West Haven, CT 06516 USA. [Ittiwut, Rungnapa; Ittiwut, Chupong; Gelernter, Joel] VA Connecticut Healthcare Syst, West Haven, CT USA. [Ittiwut, Rungnapa] Minist Publ Hlth, Inst Pathol, Dept Med Serv, Bangkok, Thailand. [Ittiwut, Chupong] Chulalongkorn Univ, Fac Med, Chulalongkorn GenePRO Ctr, Bangkok 10330, Thailand. [Cubells, Joseph F.] Emory Univ Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Weiss, Roger D.] McLean Hosp, Belmont, MA 02178 USA. [Weiss, Roger D.] Harvard Univ, Sch Med, Boston, MA USA. [Brady, Kathleen] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Oslin, David] Univ Penn Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA USA. [Farrer, Lindsay A.] Boston Univ Sch Med, Dept Med Genet Neurol Ophthalmol Genet & Genom Ep, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ Sch Publ Hlth, Dept Med Genet Neurol Ophthalmol Genet & Genom Ep, Boston, MA USA. [Kranzler, Henry R.] Univ Connecticut Sch Med, Dept Psychiat & Genet & Dev Biol, Farmington, CT USA. [Gelernter, Joel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, Joel] Dept Neurobiol, New Haven, CT USA. RP Gelernter, J (reprint author), Yale Univ Sch Med, VAMC 116A2, Dept Psychiat, 950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU NIH (NIDA) [R01 DA12690, R01 DA12849, R01 AA0175350, R01 AA11330, D43 TW06166, K24 DA022288]; GCRC [M01 RR06192]; US Department of Veterans Affairs (the VA Connecticut-Massachusetts Mental Illness Research, Education and Clinical Center (MIRECC)); Merck; ACTIVE FX Grant sponsor: NIH (NIDA); Grant numbers: R01 DA12690, R01 DA12849, R01 AA0175350, R01 AA11330, D43 TW06166, K24 DA022288; Grant sponsor: GCRC; Grant number: M01 RR06192; Grant sponsor: US Department of Veterans Affairs (the VA Connecticut-Massachusetts Mental Illness Research, Education and Clinical Center (MIRECC)).; Dr. Kranzler has been a paid consultant for Alkermes, GlaxoSmithKline, and Gilead. He has received research support from Merck. He also reports associations with Eli Lilly, Janssen, Schering Plough, Lundbeck, Alkermes, GlaxoSmithKline, Abbott, and Johnson ACTIVE) and Dr. Kranzler receives support from ACTIVE. NR 38 TC 9 Z9 9 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD SEP PY 2011 VL 156B IS 6 BP 651 EP 660 DI 10.1002/ajmg.b.31205 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 811QR UT WOS:000294228600003 PM 21656904 ER PT J AU Finney, JW Humphreys, K Kivlahan, DR Harris, AHS AF Finney, John W. Humphreys, Keith Kivlahan, Daniel R. Harris, Alex H. S. TI Why Health Care Process Performance Measures Can Have Different Relationships to Outcomes for Patients and Hospitals: Understanding the Ecological Fallacy SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID USE-DISORDER-TREATMENT; CLINICAL-OUTCOMES; CLUSTERED DATA; QUALITY-MEASURES; CONTINUING CARE; MULTILEVEL; BIAS; EXPERIENCE; MORTALITY; ROBINSON AB Relationships between health care process performance measures (PPMs) and outcomes can differ in magnitude and even direction for patients versus higher level units (e.g., health care facilities). Such discrepancies can arise because facility-level relationships ignore PPM outcome relationships for patients within facilities, may have different confounders than patient-level PPM outcome relationships, and may reflect facility effect modification of patient PPM outcome relationships. If a patient-level PPM is related to better patient outcomes, that care process should be encouraged. However, the finding in a multilevel analysis that the proportion of patients receiving PPM care across facilities nevertheless is linked to poor hospital outcomes would suggest that interventions targeting the health care facility also are needed. (Am J Public Health. 2011; 101:1635-1642. doi:10.2105/AJPH.2011.300153) C1 [Kivlahan, Daniel R.] Vet Affairs Puget Sound Hlth Care Syst, Subst Use Disorders Qual Enhancement Res Initiat, Seattle, WA USA. [Finney, John W.; Humphreys, Keith; Harris, Alex H. S.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA USA. RP Finney, JW (reprint author), VA Palo Alto Hlth Care Syst 152MPD, Ctr Hlth Care Evaluat, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM john.finney@va.gov FU Health Services Research and Development Service (HSRD); Office of Research and Development; US Department of Veterans Affairs [SUS 99-015, IIR-07-092-1]; HSR&D Substance Use Disorder Quality Enhancement Research Initiative FX Preparation of this article was supported by the Health Services Research and Development Service (HSR&D), Office of Research and Development, US Department of Veterans Affairs (grants SUS 99-015 and IIR-07-092-1), and by the HSR&D Substance Use Disorder Quality Enhancement Research Initiative. NR 48 TC 30 Z9 30 U1 1 U2 13 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 SEP PY 2011 VL 101 IS 9 BP 1635 EP 1642 DI 10.2105/AJPH.2011.300153 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 809XR UT WOS:000294090500017 PM 21778493 ER PT J AU Venkataramani, AS Fried, BJ AF Venkataramani, Atheendar S. Fried, Brian J. TI Effect of Worldwide Oil Price Fluctuations on Biomass Fuel Use and Child Respiratory Health: Evidence from Guatemala SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID INDOOR AIR-POLLUTION; DEVELOPING-COUNTRIES; EXPOSURE; INFECTIONS; HOUSEHOLD; INDONESIA; SHOCKS; COMBUSTION; MORTALITY; QUALITY AB Objectives. We examined the effect of worldwide oil price fluctuations on household fuel use and child respiratory health in Guatemala. Methods. We regressed measures of household fuel use and child respiratory health on the average worldwide oil price and a rich set of covariates. We leveraged variation in oil prices over the 6-month period of the survey to identify associations between fuel prices, fuel choice, and child respiratory outcomes. Results. A $1 (3.4% point) increase in worldwide fuel prices was associated with a 2.8% point decrease in liquid propane gasoline use (P<.05), a 0.75% point increase in wood use (P<.05), and a 1.5% point increase in the likelihood of the child reporting a respiratory symptom (P<.1). The association between oil prices and the fuel choice indicators was largest for households in the middle of the income distribution. Conclusions. Fluctuations in worldwide fuel prices affected household fuel use and, consequently, child health. Policies to help households tide over fuel price shocks or reduce pollution from biomass sources would confer positive health benefits. Such policies would be most effective if they targeted both poor and middle-income households. (Am J Public Health. 2011;101:1668-1675. doi:10.2105/AJPH.2011.300131) C1 [Venkataramani, Atheendar S.] Yale Univ, Yale Sch Publ Hlth, Div Hlth Policy & Adm, New Haven, CT USA. [Venkataramani, Atheendar S.] Washington Univ, Sch Med, St Louis, MO USA. [Fried, Brian J.] Yale Univ, Dept Polit Sci, New Haven, CT 06520 USA. RP Venkataramani, AS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,MGH Charlestown Healthcare Ctr, 73 High St, Charlestown, MA 02129 USA. NR 45 TC 3 Z9 3 U1 0 U2 5 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 SEP PY 2011 VL 101 IS 9 BP 1668 EP 1675 DI 10.2105/AJPH.2011.300131 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 809XR UT WOS:000294090500022 PM 21778480 ER PT J AU MacMahon, PJ Palmer, WE AF MacMahon, Peter J. Palmer, William E. TI A Biomechanical Approach to MRI of Acute Knee Injuries SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE anterior cruciate ligament; knee injury; mechanism; MRI ID ANTERIOR CRUCIATE LIGAMENT; MARROW EDEMA; AVULSION; FRACTURE; MECHANISMS; KINEMATICS; PATTERNS; ROTATION; FORCES; CORNER AB OBJECTIVE. MRI is routinely performed to evaluate acute complex knee injuries. This article will review the fundamental biomechanical forces underlying the most important and common injuries and correlate MRI findings with specific traumatic mechanisms. CONCLUSION. MRI findings can reveal the traumatic mechanisms in many acute knee injuries. By applying a biomechanical approach in MRI interpretation, it is possible to use easily detected lesions, such as osseous contusion and ligament rupture, to predict subtle but important abnormalities that might otherwise be missed. This systematic focused analysis enables a more accurate and rapid interpretation of knee MR studies. C1 [MacMahon, Peter J.; Palmer, William E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, Boston, MA 02214 USA. RP Palmer, WE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Musculoskeletal Imaging & Intervent, 55 Fruit St,YAW 6030, Boston, MA 02214 USA. EM wpalmer@partners.org NR 45 TC 5 Z9 5 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2011 VL 197 IS 3 BP 568 EP 577 DI 10.2214/AJR.11.7026 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 810YD UT WOS:000294165600040 PM 21862798 ER PT J AU Modarresi, S Motamedi, D Jude, CM AF Modarresi, Shahla Motamedi, Daria Jude, Cecilia Matilda TI Superior Labral Anteroposterior Lesions of the Shoulder: Part 1, Anatomy and Anatomic Variants SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE glenoid labrum; MR arthrogram; MRI; overhead athletes; shoulder pain; SLAP; sports medicine; superior labral anteroposterior tear ID MR ARTHROGRAPHY; GLENOID LABRUM; SLAP LESIONS; BICIPITAL COMPLEX; ANTEROSUPERIOR LABRUM; SUBLABRAL RECESS; CT ARTHROGRAPHY; BUFORD COMPLEX; LONG HEAD; DIAGNOSIS AB OBJECTIVE. The objectives of this article are to provide a pictorial review of labral anatomy and physiology, with particular attention to commonly seen anatomic variants and pitfalls, and to present standard imaging techniques and approaches to MRI interpretation to facilitate diagnosis and treatment of superior labral anteroposterior (SLAP) lesions. CONCLUSION. Imaging plays an important role in the diagnosis of SLAP tears. Knowledge of glenolabral anatomy, related structures and variants, proper imaging techniques, and a systematic approach to MRI interpretation is important in the diagnosis and treatment planning of the 10 types of SLAP lesions. Arthroscopy offers a means for definitive diagnosis. C1 [Modarresi, Shahla] W Los Angeles VA Med Ctr, Dept Imaging, Musculoskeletal Sect, Los Angeles, CA 90073 USA. [Motamedi, Daria] Cedars Sinai Med Ctr, Dept Imaging, Los Angeles, CA 90048 USA. [Jude, Cecilia Matilda] Olive View UCLA Med Ctr, Dept Imaging, Sylmar, CA 91342 USA. RP Modarresi, S (reprint author), W Los Angeles VA Med Ctr, Dept Imaging, Musculoskeletal Sect, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM shahlamodarresi@yahoo.com NR 38 TC 11 Z9 13 U1 2 U2 6 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2011 VL 197 IS 3 BP 596 EP 603 DI 10.2214/AJR.10.7236 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 810YD UT WOS:000294165600043 PM 21862801 ER PT J AU Modarresi, S Motamedi, D Jude, CM AF Modarresi, Shahla Motamedi, Daria Jude, Cecilia Matilda TI Superior Labral Anteroposterior Lesions of the Shoulder: Part 2, Mechanisms and Classification SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE glenoid labrum; MR arthrogram; MRI; overhead athletes; shoulder pain; SLAP; sports medicine; superior labral anteroposterior tear ID ANTERIOR-POSTERIOR LESIONS; II SLAP LESIONS; MR ARTHROGRAPHY; INTERNAL IMPINGEMENT; GLENOID LABRUM; DIAGNOSIS; REPAIR; VARIANTS; COMPLEX; TENDON AB OBJECTIVE. The objectives of this article are to discuss the 10 distinct patterns of superior labral anteroposterior (SLAP) tears to facilitate adequate diagnosis and treatment. Correlations with clinical presentation, mechanism of injury, and treatment will enhance understanding. CONCLUSION. Imaging plays an important role in the diagnosis of SLAP tears. Knowledge of glenolabral anatomy, related structures and variants, proper imaging techniques, and a systematic approach to MRI interpretation is important in the diagnosis and treatment planning of the 10 types of SLAP lesions. Arthroscopy offers a means for definitive diagnosis. C1 [Modarresi, Shahla] W Los Angeles VA Med Ctr, Dept Imaging, Musculoskeletal Sect, Los Angeles, CA 90073 USA. [Motamedi, Daria] Cedars Sinai Med Ctr, Dept Imaging, Los Angeles, CA 90048 USA. [Jude, Cecilia Matilda] Olive View UCLA Med Ctr, Dept Imaging, Sylmar, CA 91342 USA. RP Modarresi, S (reprint author), W Los Angeles VA Med Ctr, Dept Imaging, Musculoskeletal Sect, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM shahlamodarresi@yahoo.com NR 29 TC 11 Z9 12 U1 2 U2 10 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2011 VL 197 IS 3 BP 604 EP 611 DI 10.2214/AJR.11.6575 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 810YD UT WOS:000294165600044 PM 21862802 ER PT J AU Drubach, LA Connolly, SA Palmer, EL AF Drubach, Laura A. Connolly, Susan A. Palmer, Edwin L., III TI Skeletal Scintigraphy With F-18-NaF PET for the Evaluation of Bone Pain in Children SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE F-18-NaF; bone scintigraphy; pediatric imaging; PET; sports medicine; stress fractures; trauma ID POSITRON-EMISSION-TOMOGRAPHY; F-18-FLUORIDE; METASTASES; PATIENT; CANCER AB OBJECTIVE. Although not commonly used in current clinical practice, the PET agent F-18-NaF provides an excellent alternative to the standard tracers used for radionuclide bone scintigraphy. This article illustrates the use and appearance of F-18-NaF PET and shows examples of its utility in the assessment of bone pain in children. CONCLUSION. Skeletal imaging with F-18-NaF harnesses both the superior imaging characteristics of PET and the improved biodistribution of the fluoride tracer in comparison with standard nuclear techniques, resulting in excellent-quality images that can effectively be used to investigate the cause of bone pain in children. C1 [Drubach, Laura A.; Connolly, Susan A.] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Palmer, Edwin L., III] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Drubach, LA (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM laura.drubach@childrens.harvard.edu NR 14 TC 5 Z9 6 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2011 VL 197 IS 3 BP 713 EP 719 DI 10.2214/AJR.11.6670 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 810YD UT WOS:000294165600058 PM 21862816 ER PT J AU Howard, S O'Regan, K Jagannathan, J Krajewski, K Giardino, A Ramaiya, N AF Howard, Stephanie O'Regan, Kevin Jagannathan, Jyothi Krajewski, Katherine Giardino, Angela Ramaiya, Nikhil TI Extrapulmonary Small Cell Carcinoma: A Pictorial Review SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE extrapulmonary small cell; extrapulmonary small cell carcinoma; nonpulmonary small cell; oat cell carcinoma ID CANCER NETWORK; LUNG-CANCER; SURVIVAL AB OBJECTIVE. Extrapulmonary small cell carcinoma (EPSCC) is a rare, aggressive neoplasm arising from virtually any organ. Numerous oncologic studies have addressed prognostic indicators and survival rates in EPSCC, however relatively little has been published regarding the imaging features and metastatic patterns of these uncommon tumors. This article provides a pictorial review of EPSCC in multiple organs, emphasizing the imaging appearance at presentation and the radiologic patterns of recurrence/metastasis. CONCLUSION. Although the appearance of EPSCC is often nonspecific, the typical presentation is large aggressive tumors that, similar to small cell carcinoma in the lung, often respond well to local therapy but tend to recur relentlessly at distant sites. C1 [Howard, Stephanie; O'Regan, Kevin; Jagannathan, Jyothi; Krajewski, Katherine; Giardino, Angela; Ramaiya, Nikhil] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Howard, S (reprint author), Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. EM sahoward@partners.org NR 15 TC 10 Z9 12 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 2011 VL 197 IS 3 BP W392 EP W398 DI 10.2214/AJR.10.5757 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 810YD UT WOS:000294165600004 PM 21862764 ER PT J AU Sharma, AK Baig, MW Heist, EK AF Sharma, Ajay K. Baig, M. Wajid Heist, E. Kevin TI Intracardiac Thrombosis and Acute Myocardial Infarction as Initial Presentation of Antiphospholipid Syndrome SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Intracardiac thrombosis; Acute myocardial infarction; Antiphospholipid syndrome ID ANTIBODY SYNDROME; PATIENT AB Antiphospholipid syndrome is a disorder characterized by arterial or venous thrombosis, high plasma levels of antiphospholipid antibodies, recurrent fetal loss (in women) and thrombocytopenia. The authors present a case of a 28-year-old man with no significant medical history who presented with ST elevation myocardial infarction (MI) and underwent percutaneous intervention to left anterior descending artery. He was also found to have intracardiac thrombosis, thrombocytopenia, elevated activated partial thromboplastin time and persistently elevated anticardiolipin and beta-2 glycoprotein antibodies. The authors performed a literature search regarding the frequency of MI and intracardiac thrombosis as the primary presentation of antiphospholipid syndrome and the relationship of antiphospholipid antibodies with MI. C1 [Heist, E. Kevin] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Sharma, Ajay K.] Charlton Mem Hosp, Dept Internal Med, Fall River, MA USA. [Baig, M. Wajid] Charlton Mem Hosp, Dept Cardiol, Fall River, MA USA. RP Heist, EK (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM kheist@partners.org NR 12 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD SEP PY 2011 VL 342 IS 3 BP 254 EP 256 DI 10.1097/MAJ.0b013e3182267a7b PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 810WL UT WOS:000294159200017 PM 21829132 ER PT J AU Firth, PG Solomon, JB Roberts, LL Gleeson, TD AF Firth, Paul G. Solomon, James B. Roberts, Laura L. Gleeson, Todd D. TI Airway Management of Tetanus After the Haitian Earthquake: New Aspects of Old Observations SO ANESTHESIA AND ANALGESIA LA English DT Article AB Two men developed severe tetanus after the 2010 Haitian earthquake. They were admitted to the United States Naval Ship Comfort, a hospital ship sent to provide humanitarian relief. Severe masseter and intercostal muscle spasm impaired airway access and ventilation. Propofol and sevoflurane relieved the tetany, allowing airway control and ventilation without intubation or neuromuscular blocking drugs during wound debridement. Presynaptic impairment of inhibitory neurotransmitter release by tetanospasmin toxin is countered by enhancement of spinal cord postsynaptic inhibitory receptor activity by general anesthetics. Avoidance of tracheal intubation and mechanical ventilation during anesthesia may be desirable in the settings of limited resources in which tetanus usually presents. (Anesth Analg 2011; 113: 545-7) C1 [Firth, Paul G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Solomon, James B.] Natl Naval Med Ctr, Dept Anesthesia, Bethesda, MD USA. [Gleeson, Todd D.] Natl Naval Med Ctr, Dept Infect Dis, Bethesda, MD USA. [Roberts, Laura L.] Med Univ S Carolina, Dept Anesthesia & Perioperat Med, Charleston, SC 29425 USA. RP Firth, PG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM pfirth@partners.org FU Department of Anesthesia, Critical Care; Pain Medicine, Massachusetts General Hospital, Boston, MA FX Administrative costs were provided by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA. NR 9 TC 3 Z9 3 U1 0 U2 6 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 SEP PY 2011 VL 113 IS 3 BP 545 EP 547 DI 10.1213/ANE.0b013e318223cc8c PG 3 WC Anesthesiology SC Anesthesiology GA 810WO UT WOS:000294159600017 PM 21778337 ER PT J AU Hutter, MM Schirmer, BD Jones, DB Ko, CY Cohen, ME Merkow, RP Nguyen, NT AF Hutter, Matthew M. Schirmer, Bruce D. Jones, Daniel B. Ko, Clifford Y. Cohen, Mark E. Merkow, Ryan P. Nguyen, Ninh T. TI First Report from the American College of Surgeons Bariatric Surgery Center Network Laparoscopic Sleeve Gastrectomy has Morbidity and Effectiveness Positioned Between the Band and the Bypass SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 131st Annual Meeting of the American-Surgical-Association CY APR 14-16, 2011 CL Boca Raton, FL SP Amer Surg Assoc ID WEIGHT-LOSS SURGERY; SUPER-OBESE-PATIENT; BILIOPANCREATIC DIVERSION; DUODENAL SWITCH; DATA-COLLECTION; GASTRIC BYPASS; SURGICAL CARE; RECOMMENDATIONS; COMORBIDITIES; SURVIVAL AB Objective: To assess the safety and effectiveness of the laparoscopic sleeve gastrectomy (LSG) as compared to the laparoscopic adjustable gastric band (LAGB), the laparoscopic Roux-en-Y gastric bypass (LRYGB) and the open Roux-en-Y gastric bypass (ORYGB) for the treatment of obesity and obesity-related diseases. Background: LSG is a newer procedure being done with increasing frequency. However, limited data are currently available comparing LSG to the other established procedures. We present the first prospective, multiinstitutional, nationwide, clinically rich, bariatric-specific data comparing sleeve gastrectomy to the adjustable gastric band, and the gastric bypass. Methods: This is the initial report analyzing data from the American College of Surgeons-Bariatric Surgery Center Network accreditation program, and its prospective, longitudinal, data collection system based on standardized definitions and collected by trained data reviewers. Univariate and multivariate analyses compare 30-day, 6-month, and 1-year outcomes including morbidity and mortality, readmissions, and reoperations as well as reduction in body mass index (BMI) and weight-related comorbidities. Results: One hundred nine hospitals submitted data for 28,616 patients, from July, 2007 to September, 2010. The LSG has higher risk-adjusted morbidity, readmission and reoperation/intervention rates compared to the LAGB, but lower reoperation/intervention rates compared to the LRYGB and ORYGB. There were no differences in mortality. Reduction in BMI and most of the weight-related comorbidities after the LSG also lies between those of the LAGB and the LRYGB/ORYGB. Conclusion: LSG has morbidity and effectiveness positioned between the LAGB and the LRYGB/ORYGB for data up to 1 year. As obesity is a lifelong disease, longer term comparative effectiveness data are most critical, and are yet to be determined. C1 [Hutter, Matthew M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Schirmer, Bruce D.] Univ Virginia Hlth Syst, Dept Surg, Charlottesville, VA USA. [Jones, Daniel B.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles Med Ctr, Los Angeles, CA 90024 USA. [Cohen, Mark E.] Amer Coll Surg, Chicago, IL USA. [Merkow, Ryan P.] Univ Colorado Hosp, Dept Surg, Aurora, CO USA. [Nguyen, Ninh T.] Univ Calif Irvine, Dept Surg, Irvine Sch Med, Irvine, CA 92717 USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang ACC 460, Boston, MA 02114 USA. EM mhutter@partners.org FU NIBIB NIH HHS [R01 EB009362-02, R01 EB005807, R01 EB005807-06, R01 EB009362-01A2, R01 EB009362] NR 30 TC 215 Z9 218 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2011 VL 254 IS 3 BP 410 EP 422 DI 10.1097/SLA.0b013e31822c9dac PG 13 WC Surgery SC Surgery GA 811XQ UT WOS:000294252500002 PM 21865942 ER PT J AU Neal, MD Alverdy, JC Hall, DE Simmons, RL Zuckerbraun, BS AF Neal, Matthew D. Alverdy, John C. Hall, Daniel E. Simmons, Richard L. Zuckerbraun, Brian S. TI Diverting Loop Ileostomy and Colonic Lavage An Alternative to Total Abdominal Colectomy for the Treatment of Severe, Complicated Clostridium difficile Associated Disease SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 131st Annual Meeting of the American-Surgical-Association CY APR 14-16, 2011 CL Boca Raton, FL SP Amer Surg Assoc ID PSEUDOMEMBRANOUS COLITIS; CO-MORBIDITY; PREDICTORS; MORTALITY; INFECTION; OUTBREAK; DIARRHEA; SURGERY; AMERICA; STRAIN AB Objective: To determine whether a minimally invasive, colon-preserving approach could serve as an alternative to total colectomy in the treatment of severe, complicated Clostridium difficile-associated disease (CDAD). Background: C. difficile is a significant cause of morbidity and mortality worldwide. Most cases will respond to antibiotic therapy, but 3% to 10% of patients progress to a severe, complicated, or "fulminant" state of life-threatening systemic toxicity. Although the advocated surgical treatment of total abdominal colectomy with end ileostomy improves survival in severe, complicated CDAD, outcomes remain poor with associated mortality rates ranging from 35% to 80%. Methods: All patients who were diagnosed with severe, complicated ("fulminant") CDAD and were treated at the University of Pittsburgh Medical Center or VA Pittsburgh Healthcare System between June 2009 and January 2011 were treated with this novel approach. The surgical approach involved creation of a loop ileostomy, intraoperative colonic lavage with warmed polyethylene glycol 3350/electrolyte solution via the ileostomy and postoperative antegrade instillation of vancomycin flushes via the ileostomy. The primary end point for the study was resolution of CDAD. The matching number of patients treated with colectomy for CDAD preceding the initiation of this current treatment strategy was analyzed for historical comparison. Results: Forty-two patients were treated during this time period. There was no significant difference in age, sex, pharmacologic immunosuppression, and Acute Physiology and Chronic Health Evaluation-II scores between our current cohort and historical controls. The operation was accomplished laparoscopically in 35 patients (83%). This treatment strategy resulted in reduced mortality compared to our historical population (19% vs 50%; odds ratio, 0.24; P = 0.006). Preservation of the colon was achieved in 39 of 42 patients (93%). Conclusions: Loop ileostomy and colonic lavage are an alternative to colectomy in the treatment of severe, complicated CDAD resulting in reduced morbidity and preservation of the colon. C1 [Neal, Matthew D.; Hall, Daniel E.; Simmons, Richard L.; Zuckerbraun, Brian S.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA. [Alverdy, John C.] Univ Chicago, Chicago, IL 60637 USA. [Hall, Daniel E.; Zuckerbraun, Brian S.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Zuckerbraun, BS (reprint author), NW653 MUH,3459 5th Ave, Pittsburgh, PA 15213 USA. EM zuckerbraunbs@upmc.edu RI Hall, Daniel/H-4843-2013; OI Hall, Daniel/0000-0001-6382-0522 NR 31 TC 98 Z9 98 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2011 VL 254 IS 3 BP 423 EP 429 DI 10.1097/SLA.0b013e31822ade48 PG 7 WC Surgery SC Surgery GA 811XQ UT WOS:000294252500003 PM 21865943 ER PT J AU Hawn, MT Vick, CC Richman, J Holman, W Deierhoi, RJ Graham, LA Henderson, WG Itani, KMF AF Hawn, Mary T. Vick, Catherine C. Richman, Joshua Holman, William Deierhoi, Rhiannon J. Graham, Laura A. Henderson, William G. Itani, Kamal M. F. TI Surgical Site Infection Prevention Time to Move Beyond the Surgical Care Improvement Program SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 131st Annual Meeting of the American-Surgical-Association CY APR 14-16, 2011 CL Boca Raton, FL SP Amer Surg Assoc ID ANTIMICROBIAL-PROPHYLAXIS; RISK ADJUSTMENT; QUALITY; ASSOCIATION; OUTCOMES; ANTIBIOTICS; ERRORS AB Objectives: The objective of this study was to evaluate whether the Surgical Care Improvement Project (SCIP) improved surgical site infection (SSI) rates using national data at the patient level for both SCIP adherence and SSI occurrence. Background: The SCIP was established in 2006 with the goal of reducing surgical complications by 25% in 2010. Methods: National Veterans' Affairs (VA) data from 2005 to 2009 on adherence to 5 SCIP SSI prevention measures were linked to Veterans' Affairs Surgical Quality Improvement Program SSI outcome data. Effect of SCIP adherence and year of surgery on SSI outcome were assessed with logistic regression using generalized estimating equations, adjusting for procedure type and variables known to predict SSI. Correlation between hospital SCIP adherence and SSI rate was assessed using linear regression. Results: There were 60,853 surgeries at 112 VA hospitals analyzed. SCIP adherence ranged from 75% for normothermia to 99% for hair removal and all significantly improved over the study period (P < 0.001). Surgical site infection occurred after 6.2% of surgeries (1.6% for orthopedic surgeries to 11.3% for colorectal surgeries). None of the 5 SCIP measures were significantly associated with lower odds of SSI after adjusting for variables known to predict SSI and procedure type. Year was not associated with SSI (P = 0.71). Hospital SCIP performance was not correlated with hospital SSI rates (r = -0.06, P = 0.54). Conclusions: Adherence to SCIP measures improved whereas risk-adjusted SSI rates remained stable. SCIP adherence was neither associated with a lower SSI rate at the patient level, nor associated with hospital SSI rates. Policies regarding continued SCIP measurement and reporting should be reassessed. C1 [Hawn, Mary T.] Univ Alabama, Dept Surg, Sect Gastrointestinal Surg, Birmingham, AL 35294 USA. [Hawn, Mary T.; Vick, Catherine C.; Richman, Joshua; Holman, William; Deierhoi, Rhiannon J.; Graham, Laura A.] Vet Affairs Med Ctr, Ctr Med Surg Acute Care Res & Transit, Birmingham, AL USA. [Henderson, William G.] Univ Colorado Denver, Colorado Hlth Outcomes Program, Aurora, CO USA. [Itani, Kamal M. F.] Boston Univ, VA Boston Hlth Care Syst, Boston, MA 02215 USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hawn, MT (reprint author), Univ Alabama, Dept Surg, Sect Gastrointestinal Surg, 1922 7th Ave S,KB 428, Birmingham, AL 35294 USA. EM mhawn@uab.edu NR 28 TC 128 Z9 130 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2011 VL 254 IS 3 BP 494 EP 501 DI 10.1097/SLA.0b013e31822c6929 PG 8 WC Surgery SC Surgery GA 811XQ UT WOS:000294252500012 PM 21817889 ER PT J AU Nevar, PM Rikkers, LF Lillemoe, KD AF Nevar, Pamela M. Rikkers, Layton F. Lillemoe, Keith D. TI Adherence to CONSORT Abstract Reporting Suggestions in Surgical Randomized-Controlled Trials Published in Annals of Surgery Reply SO ANNALS OF SURGERY LA English DT Letter C1 [Nevar, Pamela M.; Rikkers, Layton F.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Lillemoe, Keith D.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Nevar, PM (reprint author), Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM nevar@surgery.wisc.edu NR 1 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2011 VL 254 IS 3 BP 546 EP 547 DI 10.1097/SLA.0b013e31822ada4d PG 4 WC Surgery SC Surgery GA 811XQ UT WOS:000294252500028 ER PT J AU Shahian, DM Edwards, FH Jacobs, JP Prager, RL Normand, SLT Shewan, CM O'Brien, SM Peterson, ED Grover, FL AF Shahian, David M. Edwards, Fred H. Jacobs, Jeffrey P. Prager, Richard L. Normand, Sharon-Lise T. Shewan, Cynthia M. O'Brien, Sean M. Peterson, Eric D. Grover, Frederick L. TI Public Reporting of Cardiac Surgery Performance: Part 2-Implementation SO ANNALS OF THORACIC SURGERY LA English DT Article ID BYPASS GRAFT-SURGERY; ACUTE MYOCARDIAL-INFARCTION; IN-HOSPITAL MORTALITY; NEW-YORK-STATE; OF-CARDIOLOGY FOUNDATION; QUALITY REPORT CARDS; SHORT-TERM MORTALITY; RISK-ADJUSTMENT; HEALTH-CARE; HEART-FAILURE AB Appropriate implementation is essential to create a credible public reporting system. Ideally, data should be obtained from an audited clinical data registry, and structure, process, or outcomes metrics may be reported. Composite measures are increasingly used, as are measures of appropriateness, patient satisfaction, functional status, and health-related quality of life. Classification of provider performance should use statistical criteria appropriate to the policy objectives and to the desired balance of sensitivity and specificity. Public reports should use simplified visual or tabular presentation aids that maximize correct interpretation of numerical data. Because of sample size issues, and to emphasize that cardiac surgery requires team-based care, public reporting should generally be focused at the program rather than individual surgeon level. This may also help to mitigate risk aversion, the avoidance of high-risk patients. (Ann Thorac Surg 2011;92:S12-S23) (C) 2011 by The Society of Thoracic Surgeons C1 [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Edwards, Fred H.] Univ Florida Shands Jacksonville, Jacksonville, FL USA. [Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA. [Prager, Richard L.] Univ Michigan, Ctr Hlth, Ann Arbor, MI 48109 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Shewan, Cynthia M.] Soc Thorac Surg, Chicago, IL USA. [O'Brien, Sean M.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Grover, Frederick L.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org RI O'Brien, Sean/H-6268-2013 NR 118 TC 38 Z9 38 U1 0 U2 8 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 SEP PY 2011 VL 92 IS 3 SU 1 BP S12 EP S23 DI 10.1016/j.athoracsur.2011.06.101 PG 12 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 811IL UT WOS:000294202000003 PM 21867788 ER PT J AU Shahian, DM Edwards, FH Jacobs, JP Prager, RL Normand, SLT Shewan, CM O'Brien, SM Peterson, ED Grover, FL AF Shahian, David M. Edwards, Fred H. Jacobs, Jeffrey P. Prager, Richard L. Normand, Sharon-Lise T. Shewan, Cynthia M. O'Brien, Sean M. Peterson, Eric D. Grover, Frederick L. TI Public Reporting of Cardiac Surgery Performance: Part 1-History, Rationale, Consequences SO ANNALS OF THORACIC SURGERY LA English DT Article ID NEW-YORK-STATE; BYPASS GRAFT-SURGERY; PERCUTANEOUS CORONARY INTERVENTION; QUALITY-OF-CARE; IMPROVE CLINICAL-PRACTICE; HOSPITAL MORTALITY-RATES; RISK-ADJUSTED OUTCOMES; STS NATIONAL DATABASE; HEALTH-CARE; VETERANS-AFFAIRS AB Cardiac surgical report cards have historically been mandatory. This paradigm changed when The Society of Thoracic Surgeons recently implemented a voluntary public reporting program based on benchmark analyses from its National Cardiac Database. The primary rationale is to provide transparency and accountability, thus affirming the fundamental ethical right of patient autonomy. Previous studies suggest that public reporting facilitates quality improvement, although other approaches such as confidential feedback of results and regional quality improvement initiatives are also effective. Public reporting has not substantially impacted patient referral patterns or market share. However, this may change with implementation of healthcare reform and with refinement of public reporting formats to enhance consumer interpretability. Finally, the potential unintended adverse consequences of public reporting must be monitored, particularly to assure that hospitals and surgeons remain willing to care for high-risk patients. (Ann Thorac Surg 2011;92:S2-S11) (C) 2011 by The Society of Thoracic Surgeons C1 [Shahian, David M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Edwards, Fred H.] Univ Florida Shands Jacksonville, Jacksonville, FL USA. [Jacobs, Jeffrey P.] Congenital Heart Inst Florida, St Petersburg, FL USA. [Prager, Richard L.] Univ Michigan, Ctr Hlth, Ann Arbor, MI 48109 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Shewan, Cynthia M.] Soc Thorac Surg, Chicago, IL USA. [O'Brien, Sean M.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Grover, Frederick L.] Univ Colorado, Sch Med, Dept Surg, Aurora, CO USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org RI O'Brien, Sean/H-6268-2013 NR 105 TC 54 Z9 54 U1 1 U2 15 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 SEP PY 2011 VL 92 IS 3 SU 1 BP S2 EP S11 DI 10.1016/j.athoracsur.2011.06.100 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 811IL UT WOS:000294202000002 PM 21867789 ER PT J AU Shahian, DM AF Shahian, David M. TI Public Reporting of Cardiac Surgery Performance: Introduction SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2011 VL 92 IS 3 SU 1 BP S1 EP S1 DI 10.1016/j.athoracsur.2011.06.102 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 811IL UT WOS:000294202000001 PM 21867787 ER PT J AU Hammad, MA Abdel-Bakky, MS Walker, LA Ashfaq, MK AF Hammad, Mohamed A. Abdel-Bakky, Mohamed Sadek Walker, Larry A. Ashfaq, M. K. TI Oxidized low-density lipoprotein and tissue factor are involved in monocrotaline/lipopolysaccharide-induced hepatotoxicity SO ARCHIVES OF TOXICOLOGY LA English DT Article DE Hepatotoxicity; Lipopolysaccharide; Monocrotaline; Pyrrolizidine alkaloids; Tissue factor; Oxidized low-density lipoprotein ID HUMAN ENDOTHELIAL-CELLS; SCAVENGER RECEPTOR; LIVER FIBROSIS; REACTIVE OXYGEN; IN-VITRO; CXCL16; LDL; INJURY; ADHESION; PHOSPHATIDYLSERINE AB These studies were aimed at characterizing an animal model of inflammation-induced hepatotoxicity that would mimic features of idiosyncratic liver toxicity observed in humans. An attempt was made to identify oxidative damage and the involvement of coagulation system in liver after monocrotaline (MCT) administration under the modest inflammatory condition induced by lipopolysaccharide (LPS) exposure. Mice were given MCT (200 mg/kg) or an equivalent volume of sterile saline (Veh.) po followed 4 h later by ip injection of LPS (6 mg/kg) or vehicle. Mice co-treated with MCT and LPS showed increased plasma alanine aminotransferase (ALT), decrease in platelet number, and a reduction in hematocrit. Accumulation of oxidized low-density lipoprotein (ox-LDL) was remarkably higher in the liver sections of mice co-treated with MCT and LPS compared to those given MCT or LPS alone. A similar trend was observed in the expression of CXCL16 receptor in the same liver sections. Elevated expression of tissue factor (TF) and fibrinogen was also observed in the liver sections of MCT/LPS co-treated mice. The in vitro results showed that incubation of HepG2 cells with CXCL16 antibody strongly diminished uptake of ox-LDL. Expression of ox-LDL, CXCL16, and TF represents an early event in the onset of hepatotoxicity induced by MCT/LPS; thus, it may contribute to our understanding of idiosyncratic liver injury and points to potential targets for protection or intervention. C1 [Hammad, Mohamed A.; Abdel-Bakky, Mohamed Sadek; Walker, Larry A.; Ashfaq, M. K.] Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA. [Hammad, Mohamed A.; Walker, Larry A.] Univ Mississippi, Sch Pharm, Dept Pharmacol, University, MS 38677 USA. [Hammad, Mohamed A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Abdel-Bakky, Mohamed Sadek] Al Azhar Univ, Fac Pharm, Cairo 11884, Egypt. RP Ashfaq, MK (reprint author), Univ Mississippi, Sch Pharm, Natl Ctr Nat Prod Res, University, MS 38677 USA. EM mkashfaq@olemiss.edu OI HAMMAD, MOHAMED/0000-0002-9684-2506 FU NSF [MRI 619774]; United States Department of Agriculture, Agricultural Research Service [58-6408-2-0009]; US Food and Drug Administration [5U01FD002071-09, 1U01FD003871-011] FX The authors wish to thank the Light Microscopy Core Facility members, Dr. Zia Shariat-Madar and Mr. Noah Osman (School of Pharmacy, University of Mississippi) for their assistance. The Zeiss 510-META confocal microscope service is supported through NSF Grant # MRI 619774 (ZSM). Special thanks are also due to Mrs. Lavanya Madgula, Mrs. Mona Haron and all the vivarium staff at the University of Mississippi for their help to complete the experiments. This work was supported by in part by the United States Department of Agriculture, Agricultural Research Service, Specific Cooperative agreement [58-6408-2-0009] and US Food and Drug Administration [5U01FD002071-09 and 1U01FD003871-011]. NR 35 TC 6 Z9 7 U1 2 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD SEP PY 2011 VL 85 IS 9 BP 1079 EP 1089 DI 10.1007/s00204-011-0649-6 PG 11 WC Toxicology SC Toxicology GA 810ZD UT WOS:000294169200007 PM 21279329 ER PT J AU Horbinski, C Kofler, J Yeaney, G Camelo-Piragua, S Venneti, S Louis, DN Perry, A Murdoch, G Nikiforova, M AF Horbinski, Craig Kofler, Julia Yeaney, Gabrielle Camelo-Piragua, Sandra Venneti, Sriram Louis, David N. Perry, Arie Murdoch, Geoffrey Nikiforova, Marina TI Isocitrate Dehydrogenase 1 Analysis Differentiates Gangliogliomas from Infiltrative Gliomas SO BRAIN PATHOLOGY LA English DT Article DE ganglioglioma; glioneuronal; isocitrate dehydrogenase ID ACUTE MYELOID-LEUKEMIA; IDH1 CODON 132; TUMOR RECURRENCE; MUTATIONS; COMMON; OLIGODENDROGLIOMAS; GLIOBLASTOMAS; ABERRATIONS; PROGRESSION; CANCERS AB Recent work has identified novel point mutations in isocitrate dehydrogenase 1 (IDH1) in the majority of the World Health Organization grades II and III infiltrative gliomas and secondary grade IV glioblastomas. Gangliogliomas consist of neoplastic ganglion and glial cells and, in contrast to infiltrative gliomas, are generally indolent. Yet distinguishing between a ganglioglioma and an infiltrative glioma with admixed gray matter can be difficult, perhaps accounting for some "gangliogliomas" that ultimately show aggressive behavior. In this multi-institutional study, 98 cases originally diagnosed as ganglioglioma were analyzed for IDH1 mutations, 86 of which had follow-up data available. Eight cases (8.2%) were positive for R132H IDH1 mutations; six had silent IDH2 mutations and two had nonsense IDH2 mutations. The presence of mutant IDH1 in gangliogliomas correlated with a greater risk of recurrence (P = 0.0007) and malignant transformation and/or death (P < 0.0001) compared with tumors that were IDH1 wild type. Furthermore, the age of patients with IDH1-mutant gangliogliomas was higher than those without mutations (25.5 vs. 46.1 years, P = 0.0033). IDH1/2 testing of tumors suspected of being gangliogliomas may therefore be advisable, particularly in the adult population. C1 [Horbinski, Craig] Univ Kentucky, Dept Pathol, Lexington, KY 40536 USA. [Kofler, Julia; Murdoch, Geoffrey; Nikiforova, Marina] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Yeaney, Gabrielle] Univ Rochester, Dept Pathol, Rochester, NY 14627 USA. [Camelo-Piragua, Sandra; Louis, David N.] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Camelo-Piragua, Sandra; Louis, David N.] Harvard Univ, Sch Med, Boston, MA USA. [Venneti, Sriram] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. [Perry, Arie] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. RP Horbinski, C (reprint author), Univ Kentucky, Dept Pathol, MS 112,800 Rose St, Lexington, KY 40536 USA. EM craig.horbinski@uky.edu OI Perry, Arie/0000-0002-8300-7261 FU NCI NIH HHS [K08 CA155764] NR 46 TC 32 Z9 33 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2011 VL 21 IS 5 BP 564 EP 574 DI 10.1111/j.1750-3639.2011.00480.x PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 809RG UT WOS:000294073800008 PM 21314850 ER PT J AU Pagani, O Partridge, A Korde, L Badve, S Bartlett, J Albain, K Gelber, R Goldhirsch, A AF Pagani, Olivia Partridge, Ann Korde, Larissa Badve, Sunil Bartlett, John Albain, Kathy Gelber, Richard Goldhirsch, Aron TI Pregnancy after breast cancer: if you wish, ma'am SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Review DE Breast cancer; Pregnancy; Fertility; Breast feeding ID YOUNG-WOMEN; FERTILITY PRESERVATION; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; OVARIAN RESERVE; EMBRYO CRYOPRESERVATION; REMAIN PREMENOPAUSAL; HORMONE AGONISTS; HODGKIN LYMPHOMA; FEMALE-PATIENTS AB A growing number of young breast cancer survivors consider reproductive health issues, including subsequent fertility and pregnancy, of great importance, but many questions regarding safety remain unanswered. We conducted a comprehensive literature search and review of published articles, control-matched, population-based, and co-operative group reports that addressed various aspects of pregnancy after breast cancer (patients' expectations, fertility damage, assessment and preservation, maternal and fetal outcome, breast feeding). Overall, available data support pregnancy and breast feeding after breast cancer as safe and feasible for women at low risk of recurrence. This retrospective and population-based evidence is, however, frequently incomplete; usually not representative of the entire population, it can be biased by patients' related effects or underpowered and is often not controlled for biological factors and risk determinants in the statistical model used. Before making any definitive assumption on this delicate and fundamental aspect of a woman's life after breast cancer, we should demonstrate without any reasonable doubt that the scattered information available today is scientifically sound. The Breast International Group and North American Breast Cancer Group are planning a global prospective study in young women with endocrine responsive, early breast cancer who desire pregnancy, to assess both patients' and pregnancy outcomes. The trial will include an observational phase investigating the feasibility and impact of a temporary treatment interruption to allow conception and an experimental phase investigating the optimal duration of the subsequent endocrine treatment after delivery or the last failed attempt to get pregnant. C1 [Pagani, Olivia] Osped Italiano, Inst Oncol So Switzerland IOSI, CH-6902 Viganello, Switzerland. [Pagani, Olivia] Osped Italiano, Int Breast Canc Study Grp IBCSG, CH-6902 Viganello, Switzerland. [Partridge, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Korde, Larissa] Univ Washington, Div Med Oncol, Seattle, WA 98195 USA. [Badve, Sunil] Indiana Univ, Indianapolis, IN 46260 USA. [Bartlett, John] Edinburgh Canc Res Ctr, Endocrine Canc Grp, Edinburgh, Midlothian, Scotland. [Albain, Kathy] Loyola Univ, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Gelber, Richard] Harvard Univ, Sch Publ Hlth, IBCSG Stat Ctr,Frontier Sci & Technol Res Fdn, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gelber, Richard] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Goldhirsch, Aron] Swiss Ctr Breast Hlth, Lugano, Switzerland. RP Pagani, O (reprint author), Osped Italiano, Inst Oncol So Switzerland IOSI, CH-6902 Viganello, Switzerland. EM Olivia.pagani@ibcsg.org; Ann_Partridge@dfci.harvard.edu; lkorde@u.washington.edu; sbadve@iupui.edu; John.Bartlett@ed.ac.uk; kalbain@lumc.edu; gelber@jimmy.harvard.edu; aron.goldhirsch@ibcsg.org OI Gnant, Michael/0000-0003-1002-2118 FU Breast Cancer Research Foundation FX The authors express their gratitude to Mrs Kris Vantongelen for coordinating the work of the Breast International Group and North American Breast Cancer Group Endocrine Working Group. The Breast International Group and the North American Breast Cancer Group Collaboration is supported by a grant of The Breast Cancer Research Foundation. NR 73 TC 40 Z9 42 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2011 VL 129 IS 2 BP 309 EP 317 DI 10.1007/s10549-011-1643-7 PG 9 WC Oncology SC Oncology GA 804DI UT WOS:000293634000002 PM 21698406 ER PT J AU Dominici, L Najita, J Hughes, M Niland, J Marcom, P Wong, YN Carter, B Javid, S Edge, S Burstein, H Golshan, M AF Dominici, Laura Najita, Julie Hughes, Melissa Niland, Joyce Marcom, Paul Wong, Yu-ning Carter, Bradford Javid, Sara Edge, Stephen Burstein, Harold Golshan, Mehra TI Surgery of the primary tumor does not improve survival in stage IV breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Stage IV breast cancer; Surgery; Survival; Mastectomy ID RESECTION; THERAPY; IMPACT; RECONSTRUCTION; CHEMOTHERAPY; SITE AB We sought to evaluate the survival of patients who received breast surgery prior to any other breast cancer therapy following a metastatic diagnosis. Standard treatment for stage IV breast cancer is systemic therapy without resection of the primary tumor. Registry-based studies suggest that resection of the primary tumor may improve survival in stage IV cancer. We performed a retrospective analysis using data from the National Comprehensive Cancer Network (NCCN) Breast Cancer Outcomes Database. Patients were eligible if they had a metastatic breast cancer diagnosis at presentation with disease at a distant site and either received surgery prior to any systemic therapy or received systemic therapy only. Eligible patients who did not receive surgery were matched to those who received surgery based on age at diagnosis, ER, HER2, and number of metastatic sites. To determine whether estimates from the matched analysis were consistent with estimates that could be obtained without matching univariate and multivariable analyses of the unmatched sample were also conducted. There were 1,048 patients in the NCCN database diagnosed with stage IV breast cancer from 1997 to 2007. 609 metastatic breast cancer patients were identified as eligible for the study. Among the 551 patients who had data available for matching, 236 patients who did not receive surgery were matched to 54 patients who received surgery. Survival was similar between the groups with a median of 3.4 years in the nonsurgery group and 3.5 years in the surgery group. The groups were similar after adjusting for the presence of lung metastases and use of trastuzumab therapy (HR = 0.94, CI 0.83-1.08, P = 0.38). When matching for the variables associated with a survival benefit in previous studies, surgery was not shown to improve survival in the stage IV setting for this subset. C1 [Dominici, Laura; Golshan, Mehra] Brigham & Womens Hosp, Dept Surg Oncol, Boston, MA 02115 USA. [Dominici, Laura; Najita, Julie; Hughes, Melissa; Burstein, Harold; Golshan, Mehra] Dana Farber Canc Inst, Boston, MA 02115 USA. [Niland, Joyce] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Marcom, Paul] Duke Univ, Durham, NC USA. [Wong, Yu-ning] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Carter, Bradford] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Javid, Sara] Univ Washington, Seattle, WA 98195 USA. [Edge, Stephen] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg Oncol, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org FU National Cancer Institute [CA089393]; National Comprehensive Cancer Network FX Supported in part by Grant No. CA089393 from the National Cancer Institute to Dana-Farber Cancer Institute and by the National Comprehensive Cancer Network. NR 23 TC 26 Z9 27 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2011 VL 129 IS 2 BP 459 EP 465 DI 10.1007/s10549-011-1648-2 PG 7 WC Oncology SC Oncology GA 804DI UT WOS:000293634000014 PM 21713372 ER PT J AU Esserman, LJ Moore, DH Tsing, PJ Chu, PW Yau, C Ozanne, E Chung, RE Tandon, VJ Park, JW Baehner, FL Kreps, S Tutt, ANJ Gillett, CE Benz, CC AF Esserman, Laura J. Moore, Dan H. Tsing, Pamela J. Chu, Philip W. Yau, Christina Ozanne, Elissa Chung, Robert E. Tandon, Vickram J. Park, John W. Baehner, Frederick L. Kreps, Stig Tutt, Andrew N. J. Gillett, Cheryl E. Benz, Christopher C. TI Biologic markers determine both the risk and the timing of recurrence in breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Hormone therapy; Risk partitioning; Risk; Recurrence; Gene signatures ID TERM-FOLLOW-UP; EXPRESSION SIGNATURE; PROGNOSTIC SIGNATURE; MOLECULAR PORTRAITS; DISTANT METASTASIS; THERAPY; VALIDATION; ADJUVANT; SURVIVAL; WOMEN AB Breast cancer has a long natural history. Established and emerging biologic markers address overall risk but not necessarily timing of recurrence. 346 adjuvant na < ve breast cancer cases from Guy's Hospital with 23 years minimum follow-up and archival blocks were recut and reassessed for hormone-receptors (HR), HER2-receptor and grade. Disease-specific survival (DSS) was analyzed by recursive partitioning. To validate insights from this analysis, gene-signatures (proliferative and HR-negative) were evaluated for their ability to predict early versus late metastatic risk in 683 node-negative, adjuvant na < ve breast cancers annotated with expression microarray data. Risk partitioning showed that adjuvant na < ve node-negative outcome risk was primarily partitioned by tumor receptor status and grade but not tumor size. HR-positive and HER2-negative (HRpos) risk was partitioned by tumor grade; low grade cases have very low early risk but a 20% fall-off in DSS 10 or more years after diagnosis. Higher grade HRpos cases have risk over > 20 years. Triple-negative (Tneg) and HER2-positive (HER2pos) cases DSS events occurred primarily within the first 5 years. Among node-positive cases, only low grade conferred late risk, suggesting that proliferative gene signatures that identify proliferation would be important for predicting early but not late recurrence. Using pooled data from four publicly available data sets for node-negative tumors annotated with gene expression and outcome data, we evaluated four prognostic gene signatures: two proliferation-based and two immune function-based. Tumor proliferative capacity predicted early but not late metastatic risk for HRpos cases. The immune function or HRneg specific signatures predicted only early metastatic risk in Tneg and HER2pos cases. Breast cancer prognostic signatures need to inform both risk and timing of metastatic events and may best be applied within subsets. Current signatures predict for outcome risk within 5 years of diagnosis. Predictors of late risk for HR positive disease are needed. C1 [Esserman, Laura J.] Univ Calif San Francisco, Carol Franc Buck Breast Care Ctr, San Francisco, CA 94115 USA. [Esserman, Laura J.; Tsing, Pamela J.; Chu, Philip W.; Tandon, Vickram J.; Kreps, Stig] Univ Calif San Francisco, Dept Surg & Radiol, San Francisco, CA 94115 USA. [Moore, Dan H.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94115 USA. [Baehner, Frederick L.] Univ Calif San Francisco, Dept Pathol & Lab Med, San Francisco, CA 94115 USA. [Yau, Christina; Benz, Christopher C.] Buck Inst Aging, Novato, CA USA. [Ozanne, Elissa] Massachusetts Gen Hosp, Dept Radiol & Outcomes, Boston, MA 02114 USA. [Park, John W.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. [Tutt, Andrew N. J.] Guys Hosp, Breakthrough Breast Canc Res Unit, Kings Hlth Partners AHSC, London SE1 9RT, England. [Gillett, Cheryl E.] Kings Coll London, Guys Hosp, London WC2R 2LS, England. RP Esserman, LJ (reprint author), Univ Calif San Francisco, Carol Franc Buck Breast Care Ctr, 1600 Divisadero St,Box 1710, San Francisco, CA 94115 USA. EM laura.esserman@ucsfmedctr.org FU Early Detection Research Network (EDRN) initiative of the National Cancer Institute [5 UO1 CA111234]; Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre FX This work was supported by the Early Detection Research Network (EDRN) initiative of the National Cancer Institute (5 UO1 CA111234); and from the Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. NR 39 TC 36 Z9 36 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 2011 VL 129 IS 2 BP 607 EP 616 DI 10.1007/s10549-011-1564-5 PG 10 WC Oncology SC Oncology GA 804DI UT WOS:000293634000030 PM 21597921 ER PT J AU Potter, P Eisenberg, S Cain, KC Berry, DL AF Potter, Pamela Eisenberg, Seth Cain, Kevin C. Berry, Donna L. TI Orange Interventions for Symptoms Associated With Dimethyl Sulfoxide During Stem Cell Reinfusions A Feasibility Study SO CANCER NURSING LA English DT Article DE Adverse effects; Aromatherapy; Chemically induced; Complementary therapies; Dimethyl sulfoxide; Hematopoietic stem cell transplantation; Holistic nursing; Methods; Nausea; Therapy; Vomiting ID PERIPHERAL-BLOOD; TRANSPLANTATION; AROMATHERAPY; INFUSION; NAUSEA; TRIAL; ODOR AB Background: For over 2 decades, oncology nurses at a regional comprehensive cancer center offered sliced oranges to patients during the reinfusion of autologous hematopoietic progenitor cells (HPCs) to relieve symptoms associated with the preservative dimethyl sulfoxide (DMSO). Objective: This randomized pilot study examined feasibility and efficacy of sliced orange intervention (OI), orange aromatherapy intervention (OAI), or deep breathing (control) to address unpleasant adverse effects during HPC infusion. Methods: Orange intervention sniffed or tasted a quartered orange, OAI sniffed orange aromatherapy, and control took deep breaths. Perceived "symptom intensity" for tickle/cough urge, nausea, retching, and perceived "relief" were measured on 0- to 10-point numerical scales. Results: Sixty of 72 eligible patients consented to participate and were randomized to OI (n = 19), OAI (n = 23), or control (n = 18). Study personnel successfully administered study procedures. Over the course of 2 bags of cells infused, the OI group reported significantly greater relief with the intervention (P = .032). Among participants less than 90 kg, OI group reported significantly lower symptom intensity (P = .012). Conclusions: Results suggest a feasible protocol and potential efficacy of sliced oranges for treating symptoms associated with DMSO-preserved stem cells. Study procedures provide a tested protocol for future studies. Follow-up study is warranted to confirm these findings and evaluate other treatment options. Implications for Practice: Oranges offer a simple, noninvasive intervention for relieving symptoms associated with DMSO preservative during autologous HPC infusion. C1 [Potter, Pamela] Univ Portland, Sch Nursing, Portland, OR 97203 USA. [Eisenberg, Seth] Seattle Canc Care Alliance, Infus Serv, Seattle, WA USA. [Cain, Kevin C.] Off Nursing Res, Seattle, WA USA. [Cain, Kevin C.] Dept Biostatist, Seattle, WA USA. [Berry, Donna L.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Potter, P (reprint author), Univ Portland, Sch Nursing, 5000 N Willamette Blvd, Portland, OR 97203 USA. EM potter@up.edu FU Puget Sound Oncology Nursing Society; National Institute of Nursing Research through University of Washington [T32NR007106] FX Funding support was provided by the Puget Sound Oncology Nursing Society and National Institute of Nursing Research through University of Washington Biobehavioral Nursing Research Training Grant T32NR007106. NR 27 TC 7 Z9 7 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD SEP-OCT PY 2011 VL 34 IS 5 BP 361 EP 368 DI 10.1097/NCC.0b013e31820641a5 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 810VT UT WOS:000294156700007 PM 21372706 ER PT J AU Bae, S Yalamarti, B Ke, QG Choudhury, S Yu, H Karumanchi, SA Kroeger, P Thadhani, R Kang, PM AF Bae, Soochan Yalamarti, Bhargavi Ke, Qingen Choudhury, Sangita Yu, Hyeon Karumanchi, S. Ananth Kroeger, Paul Thadhani, Ravi Kang, Peter M. TI Preventing progression of cardiac hypertrophy and development of heart failure by paricalcitol therapy in rats SO CARDIOVASCULAR RESEARCH LA English DT Article DE Dahl rats; ACE inhibitor; BNP; Fibrosis; Microarrays ID VITAMIN-D DEFICIENCY; RENIN-ANGIOTENSIN SYSTEM; KINASE-C BETA; D-RECEPTOR; CARDIOVASCULAR-DISEASE; 1,25-DIHYDROXYVITAMIN D-3; EXPRESSION; APOPTOSIS; OVEREXPRESSION; PROLIFERATION AB Aims Vitamin D deficiency is associated with cardiac hypertrophy and heart failure, and vitamin D therapy prevents the progression of cardiac hypertrophy in animal models. Here, we examine whether vitamin D therapy prevents progression of pre-existing cardiac hypertrophy and development of heart failure. Methods and results When male Dahl salt-sensitive rats were fed a high salt (HS) diet, all rats developed cardiac hypertrophy after 5 weeks. Thereafter, rats were treated with vehicle (V), paricalcitol (PC, an active vitamin D analogue, at 200 ng, IP 3x/week), enalapril (EP, 90 mu g/day), and PC + EP. All groups were continued on the HS diet and evaluated after 4 weeks of therapy. The PC and PC + EP groups, but not the V and EP only groups, showed significant prevention of progression of pre-existing cardiac hypertrophy. The signs of decompensated heart failure were evident in the vehicle-treated group; these heart failure parameters significantly improved with PC, EP or PC + EP therapy. The expression of PKC alpha, which is regulated by Ca(2+) and known to stimulate cardiac hypertrophy, was significantly increased in the vehicle group, and PC, EP or PC + EP effectively decreased PKC alpha activation. We also observed normalization of genetic alterations during progression to heart failure with PC treatment. Conclusion PC treatment resulted in both the prevention of progression of pre-existing cardiac hypertrophy and the development of heart failure, compared with improvement in progression to heart failure by EP alone. These beneficial findings in heart were associated with inhibition of PKC alpha activation and reversal of gene alterations. C1 [Thadhani, Ravi] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Bae, Soochan; Yalamarti, Bhargavi; Ke, Qingen; Choudhury, Sangita; Yu, Hyeon; Kang, Peter M.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Yu, Hyeon; Kang, Peter M.] Chonbuk Natl Univ, Dept BIN Fus Technol, Jeonju, South Korea. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. [Kroeger, Paul] Abbott Labs, Abbott Pk, IL 60064 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, Bullfinch 127, Boston, MA 02114 USA. EM thadhani.r@mgh.harvard.edu; pkang@bidmc.harvard.edu RI Bae, Soochan/H-1315-2011 FU National Institutes of Health [RO1 HL091998]; Ministry of Education, Science and Technology, South Korea [R31-20029]; Abbott Laboratories; Howard Hughes Medical Institute FX This work was supported by the grants from National Institutes of Health RO1 HL091998 (P. M. K.), the World Class University program (R31-20029) from Ministry of Education, Science and Technology, South Korea (P. M. K.), Abbott Laboratories (P. M. K. and R. T.) and the Howard Hughes Medical Institute (S.A.K.). NR 37 TC 33 Z9 35 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD SEP 1 PY 2011 VL 91 IS 4 BP 632 EP 639 DI 10.1093/cvr/cvr133 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 809PN UT WOS:000294069300011 PM 21565836 ER PT J AU Sharma, A Avery, L Novelline, R AF Sharma, Ashish Avery, Laura Novelline, Robert TI Seizure-induced lumbar burst fracture associated with conus medullaris-cauda equina compression SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Article DE seizure; burst fracture; vertebra; conus medullaris; cauda equina ID EPILEPTIC SEIZURES; PRESENTING FEATURE; SYNDROME SECONDARY; SPINE; DIAGNOSIS AB A 36-year-old male developed a burst fracture of the L1 vertebra following a seizure. The patient experienced conus-cauda equina compression resulting in urinary retention and patchy sensory loss. An MRI of the spine revealed short tau inversion recovery (STIR) hyperintensity at L1 with 70% loss of vertebral body height, 8-mm posterior bony retropulsion into the spinal canal and T2-weighted hyperintensity in the cord, which is consistent with cord edema. A thorough physical exam and imaging is critical for immediate diagnosis of spine injuries to prevent grave neurological complications. C1 [Sharma, Ashish; Avery, Laura; Novelline, Robert] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sharma, A (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM ashishdoc84@yahoo.co.in NR 25 TC 2 Z9 2 U1 0 U2 2 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD SEP PY 2011 VL 17 IS 3 BP 199 EP 204 DI 10.4261/1305-3825.DIR.3638-10.2 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 811HL UT WOS:000294197400003 PM 20717887 ER PT J AU Oklu, R Hesketh, R Wicky, S Metcalfe, J AF Oklu, Rahmi Hesketh, Robin Wicky, Stephan Metcalfe, James TI TGF beta/activin signaling pathway activation in intimal hyperplasia and atherosclerosis SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Article DE atherosclerosis; coronary artery disease; vascular intima; immunohistochemistry ID AMERICAN-HEART-ASSOCIATION; GROWTH-FACTOR-BETA; SMOOTH-MUSCLE-CELLS; ENDOTHELIAL-CELLS; VASCULAR-LESIONS; EXPRESSION; DISEASE; ATHEROGENESIS; ADHESION; RECEPTOR AB PURPOSE Intimal hyperplasia and atherosclerosis are the Achilles' heels of vascular interventions. Many cytokines and growth factors have been shown to mediate these pathological processes. There are conflicting data concerning the expression of transforming growth factor-beta 1 (TGF beta 1) antigen in human intimal hyperplasia and atherosclerotic lesions and conflicting views about whether TGF beta 1 is pro- or anti-atherogenic. The presence of TGF beta 1 is not sufficient to infer activation of its signaling pathway because TGF beta 1 may be present in inactive complexes. MATERIALS AND METHODS A sensitive immuno-fluorescence assay (cyanine-3 tyramide signal amplification system) was used on human coronary artery and aorta sections with early or advanced stage lesions to detect TGF beta 1, activin, Smad2-P, a marker of the activated TGF beta 1/activin pathway and components of latent TGF beta complexes. RESULTS All antigens were readily detected in the media and neointima of early stage lesions. The levels were either reduced or undetectable in the media of advanced lesions but were increased in the neointima in areas of high cell density. In marked contrast to activin, TGF beta 1 and LAP1 expression levels were closely correlated with Smad2-P throughout the artery wall. CONCLUSION Discrepancies in previous data for TGF beta 1 expression are probably due to assay sensitivity. TGF beta 1, but not activin, expression is consistently correlated with Smad pathway activation in the artery wall. The pattern of Smad2 activation supports a model in which TGF beta/activin signaling is anti-atherogenic in the media of normal artery walls but is equally compatible with an anti-atherogenic or pro-atherogenic response to TGF beta/activin in the neointima of lesions. C1 [Oklu, Rahmi; Wicky, Stephan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Vasc Imaging & Intervent, Boston, MA 02115 USA. [Hesketh, Robin; Metcalfe, James] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. RP Oklu, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Vasc Imaging & Intervent, Boston, MA 02115 USA. EM roklu@partners.org FU British Heart Foundation (BHF) FX This work was supported by a program grant from the British Heart Foundation (BHF) to JM. RO is a Koc scholar. NR 32 TC 2 Z9 3 U1 0 U2 1 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD SEP PY 2011 VL 17 IS 3 BP 290 EP 296 DI 10.4261/1305-3825.DIR.3844-10.1 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 811HL UT WOS:000294197400018 PM 20954112 ER PT J AU Franklin, TR Wang, Z Sciortino, N Harper, D Li, Y Hakun, J Kildea, S Kampman, K Ehrman, R Detre, JA O'Brien, CP Childress, AR AF Franklin, Teresa R. Wang, Ze Sciortino, Nathan Harper, Derek Li, Yin Hakun, Jonathan Kildea, Susan Kampman, Kyle Ehrman, Ron Detre, John A. O'Brien, Charles P. Childress, Anna Rose TI Modulation of resting brain cerebral blood flow by the GABA B agonist, baclofen: A longitudinal perfusion fMRI study SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Baclofen; GABA B agonist; Resting baseline perfusion fMRI; Addiction; Limbic circuitry; Cerebral blood flow ID VENTRAL TEGMENTAL AREA; DUAL-PROBE MICRODIALYSIS; PLACEBO-CONTROLLED TRIAL; ORBITOFRONTAL CORTEX; CIGARETTE-SMOKING; MESOLIMBIC DOPAMINE; NICOTINE DEPENDENCE; PREFRONTAL CORTEX; LIMBIC ACTIVATION; BIPOLAR DISORDER AB Background: Preclinical studies confirm that the GABA B agonist, baclofen blocks dopamine release in the reward-responsive ventral striatum (VS) and medial prefrontal cortex, and consequently, blocks drug motivated behavior. Its mechanism in humans is unknown. Here, we used continuous arterial spin labeled (CASL) perfusion fMRI to examine baclofen's effects on blood flow in the human brain. Methods: Twenty-one subjects (all smokers, 12 females) were randomized to receive either baclofen (80 mg/day; N = 10) or placebo (N = 11). A five minute quantitative perfusion fMRI resting baseline (RB) scan was acquired at two time points; prior to the dosing regimen (Time 1) and on the last day of 21 days of drug administration (Time 2). SPM2 was employed to compare changes in RB from Time 1 to 2. Results: Baclofen diminished cerebral blood flow (CBF) in the VS and mOFC and increased it in the lateral OFC, a region involved in suppressing previously rewarded behavior. CBF in bilateral insula was also blunted by baclofen (T values ranged from -11.29 to 15.3 at p = 0.001, 20 contiguous voxels). CBF at Time 2 was unchanged in placebo subjects. There were no differences between groups in side effects or cigarettes smoked per day (at either time point). Conclusions: Baclofen's modulatory actions on regions involved in motivated behavior in humans are reflected in the resting state and provide insight into the underlying mechanism behind its potential to block drug-motivated behavior, in preclinical studies, and its putative effectiveness as an anti-craving/anti-relapse agent in humans. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Franklin, Teresa R.] Univ Penn, Dept Psychiat, Ctr Studies Addict, Philadelphia, PA 19104 USA. [Detre, John A.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Detre, John A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Kampman, Kyle; Ehrman, Ron; O'Brien, Charles P.; Childress, Anna Rose] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Franklin, TR (reprint author), Univ Penn, Dept Psychiat, Ctr Studies Addict, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM franklin_t@mail.trc.upenn.edu RI Wang, Ze/A-1043-2007 FU NIH [DA015149, K01 DA 015426-011A1, 5-P60-DA-005186-18, NS045839, BCS-0224007, RR02305]; Alexander Foundation; GCRC of the University of Pennsylvania FX Work supported by NIH grants DA015149, K01 DA 015426-011A1, 5-P60-DA-005186-18, and NS045839, BCS-0224007, RR02305, The Alexander Foundation and the GCRC of the University of Pennsylvania NR 77 TC 19 Z9 19 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2011 VL 117 IS 2-3 BP 176 EP 183 DI 10.1016/j.drugalcdep.2011.01.015 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 811TZ UT WOS:000294240300013 PM 21333466 ER PT J AU Cantero, MD Cantiello, HF AF del Rocio Cantero, Maria Cantiello, Horacio F. TI Effect of lithium on the electrical properties of polycystin-2 (TRPP2) SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE TRP channels; Absolute rate theory; Anomalous molar fraction; Primary cilia ID RENAL EPITHELIAL-CELLS; SINGLE-FILE PORE; CATION CHANNEL; KIDNEY-DISEASE; SODIUM-CHANNELS; ION-TRANSPORT; PRIMARY CILIA; SELECTIVITY; PERMEATION; BLOCK AB Polycystin-2 (PC2, TRPP2) is a TRP-type, non-selective cation channel whose dysfunction is implicated in changes in primary cilium structure and genesis of autosomal dominant polycystic kidney disease (ADPKD). Lithium (Li(+)) is a potent pharmaceutical agent whose effect on cell function is largely unknown. In this work, we explored the effect of Li(+) on PC2 channel function. In vitro translated PC2 was studied in a lipid bilayer reconstitution system exposed to different chemical conditions such as Li(+) or K(+) chemical gradients and different symmetrical concentrations of either cation. Li(+) inhibited PC2 function only from the external side, by decreasing the single-channel conductance and modifying the reversal potential consistent with both permeability to and blockage of the channel. When a chemical gradient was imposed, the PC2 single-channel conductance was 144 pS and 107 pS for either K(+) or Li(+), respectively. Data were analysed in terms of the Goldman-Hodgkin-Katz approximation and energy models based on absolute rate theory to understand the mechanism(s) of Li(+) transport and blockage of PC2. The 2S3B model better explained the findings, including saturation, anomalous mole fraction, non-linearity of the current-voltage curves under bi-ionic conditions and concentration dependence of permeability ratios. The data indicate that Li(+) modifies PC2 channel function, whose effect unmasks a high-affinity binding site for this ion, and an intrinsic asymmetry in the pore structure of the channel. The findings provide insights into possible mechanism(s) of Li(+) regulation of ciliary length and dysfunction mediated by this cation. C1 [Cantiello, Horacio F.] Massachusetts Gen Hosp East, Div Nephrol, Dept Med, Charlestown, MA 02129 USA. [Cantiello, Horacio F.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [del Rocio Cantero, Maria; Cantiello, Horacio F.] UBA, Catedra Biofis, Fac Odontol, Buenos Aires, DF, Argentina. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp East, Div Nephrol, Dept Med, Charlestown, MA 02129 USA. EM cantiello@helix.mgh.harvard.edu FU NIH [DK077079] FX The authors are members of the Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Argentina. The authors are deeply grateful to Dr. Patricia Bonazzola, for constant and unconditional support and encouragement, and Sumit Lal, for excellent technical support. The authors gratefully acknowledge partial support of this study by NIH ARRA award DK077079. NR 45 TC 6 Z9 6 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD SEP PY 2011 VL 40 IS 9 BP 1029 EP 1042 DI 10.1007/s00249-011-0715-2 PG 14 WC Biophysics SC Biophysics GA 810GB UT WOS:000294112600002 ER PT J AU Howard, TE Yanover, C Mahlangu, J Krause, A Viel, KR Kasper, CK Pratt, KP AF Howard, T. E. Yanover, C. Mahlangu, J. Krause, A. Viel, K. R. Kasper, C. K. Pratt, K. P. TI Haemophilia management: time to get personal? SO HAEMOPHILIA LA English DT Review DE antigen-presentation repertoire; factor VIII inhibitor; haemophilia A; HLA class II; non synonymous-SNPs; pharmacogenetics ID FACTOR-VIII GENE; RECOMBINANT FACTOR-VIII; PREVIOUSLY UNTREATED PATIENTS; T-CELL RESPONSES; INHIBITOR DEVELOPMENT; RISK-FACTORS; HAPLOTYPE FREQUENCIES; AMERICAN POPULATION; AFRICAN-AMERICAN; IMMUNE-RESPONSE AB The possibility of alloimmunization in patients receiving protein replacement therapy depends on (at least) three risk factors, which are necessary concomitantly but insufficient alone. The first is the degree of structural difference between the therapeutic protein and the patient's own endogenous protein, if expressed. Such differences depend on the nature of the disease mutation and the pre-mutation endogenous protein structure as well as on post-translational changes and sequence-engineered alterations in the therapeutic protein. Genetic variations in the recipients' immune systems comprise the second set of risk determinants for deleterious immune responses. For example, the limited repertoire of MHC class II isomers encoded by a given person's collection of HLA genes may or may not be able to present a 'foreign' peptide(s) produced from the therapeutic protein - following its internalization and proteolytic processing - on the surface of their antigen-presenting cells (APCs). The third (and least characterized) variable is the presence or absence of immunologic 'danger signals' during the display of foreign-peptide/MHC-complexes on APCs. A choice between existing therapeutic products or the manufacture of new proteins, which may be less immunogenic in some patients or patient populations, may require prior definition of the first two of these variables. This leads then to the possibility of developing personalized therapies for disorders due to genetic deficiencies in endogenous proteins, such as haemophilia A and B. [Correction made after online publication 11 July 2011: several critical corrections have been made to the abstract]. C1 [Howard, T. E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA 90073 USA. [Howard, T. E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Howard, T. E.] Univ So Calif, Keck Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90033 USA. [Yanover, C.] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Mahlangu, J.; Krause, A.] Univ Witwatersrand, Johannesburg, South Africa. [Viel, K. R.] St Josephs Translat Res Inst, Atlanta, GA USA. [Kasper, C. K.] Orthoped Hosp, Los Angeles, CA USA. [Kasper, C. K.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Pratt, K. P.] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Pratt, K. P.] Univ Washington, Div Hematol, Seattle, WA 98195 USA. RP Howard, TE (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Bldg 500,Rm 1258, Los Angeles, CA 90073 USA. EM tom.howard@va.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 FU ARRA [1RC2-HL101851, HL-71130, HL-72533]; Bayer Hemophilia Awards Program; CSL Behring Foundation FX We thank Drs Kenneth Mann, David Lillicrap, Georg Lemm, Arthur Thompson and Glenn Pierce for critical reading of the manuscript and helpful suggestions. Support for this study included the ARRA-funded NIH/NHLBI grant 1RC2-HL101851 (TEH and KPP), the NIH/NHLBI grants HL-71130 and HL-72533 (TEH), and grants from the Bayer Hemophilia Awards Program (KPP and TEH) and the CSL Behring Foundation (KPP). We thank the following Community Advisory Board members who reviewed the manuscript and who are providing ethical oversight for studies associated with NIH-1RC2-HL101851: Dr Louis Aledort (Chair), Ms Faye Wattleton, Ms Toni Allen-Ellingson, Ms Oleta Fitzgerald, Dr William Hobbs, and Dr Yvette Latchman. NR 47 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD SEP PY 2011 VL 17 IS 5 BP 721 EP 728 DI 10.1111/j.1365-2516.2011.02517.x PG 8 WC Hematology SC Hematology GA 811AS UT WOS:000294174300035 PM 21649795 ER PT J AU Chen, HC Vaid, J Boas, DA Bortfeld, H AF Chen, Hsin-Chin Vaid, Jyotsna Boas, David A. Bortfeld, Heather TI Examining the Phonological Neighborhood Density Effect Using Near Infrared Spectroscopy SO HUMAN BRAIN MAPPING LA English DT Article DE optical imaging; phonological processing; phonological neighbors; lexical decision; hemodynamic measure; blood oxygenation; NIRS; visual word recognition ID VISUAL WORD RECOGNITION; EVENT-RELATED FMRI; LEXICAL ACTIVATION; TIME-COURSE; FREQUENCY; MEG; PROBABILITY; SIMILARITY; DESIGNS; ACCESS AB Phonological density refers to the number of words that can be generated by replacing a phoneme in a target word with another phoneme in the same position. Although the precise nature of the phonological neighborhood density effect is not firmly established, many behavioral psycholinguistic studies have shown that visual recognition of individual words is influenced by the number and type of neighbors the words have. This study explored neurobehavioral correlates of phonological neighborhood density in skilled readers of English using near infrared spectroscopy. On the basis of a lexical decision task, our findings showed that words with many phonological neighbors (e. g., FRUIT) were recognized more slowly than words with few phonological neighbors (e. g., PROOF), and that words with many neighbors elicited significantly greater changes in blood oxygenation in the left than in the right hemisphere of the brain, specifically in the areas BA 22/39/40. In previous studies these brain areas have been implicated in fine-grained phonological processing in readers of English. The present findings provide the first demonstration that areas BA 22/39/40 are also sensitive to phonological density effects. Hum Brain Mapp 32:1363-1370, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Chen, Hsin-Chin] Natl Chung Cheng Univ, Dept Psychol, Chiayi, Taiwan. [Vaid, Jyotsna] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Boas, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Bortfeld, Heather] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Bortfeld, Heather] Haskins Labs Inc, New Haven, CT USA. RP Chen, HC (reprint author), Natl Chung Cheng Univ, Dept Psychol, 168 Univ Rd, Chiayi, Taiwan. EM psyhcc@ccu.edu.tw OI Bortfeld, Heather/0000-0002-3545-5449 FU American Psychological Association, College of Liberal Arts, Texas AM University; James S. McDonnell Foundation [HD046533] FX Contract grant sponsor: To Hsin-Chin Chen: American Psychological Association Dissertation Research Award, College of Liberal Arts Dissertation Research Award, Texas A&M University. To Heather Bortfeld: HD046533, James S. McDonnell Foundation 21st Century Research Award. NR 31 TC 3 Z9 4 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2011 VL 32 IS 9 BP 1363 EP 1370 DI 10.1002/hbm.21115 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 811DR UT WOS:000294182900002 PM 20690126 ER PT J AU Smith, BD Bentzen, SM Correa, CR Hahn, CA Hardenbergh, PH Ibbott, GS McCormick, B McQueen, JR Pierce, LJ Powell, SN Recht, A Taghian, AG Vicini, FA White, JR Haffty, BG AF Smith, Benjamin D. Bentzen, Soren M. Correa, Candace R. Hahn, Carol A. Hardenbergh, Patricia H. Ibbott, Geoffrey S. McCormick, Beryl McQueen, Julie R. Pierce, Lori J. Powell, Simon N. Recht, Abram Taghian, Alphonse G. Vicini, Frank A. White, Julia R. Haffty, Bruce G. TI FRACTIONATION FOR WHOLE BREAST IRRADIATION: AN AMERICAN SOCIETY FOR RADIATION ONCOLOGY (ASTRO) EVIDENCE-BASED GUIDELINE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Breast cancer; Hypofractionation; Evidence-based guideline; Breast conserving therapy ID RANDOMIZED CLINICAL-TRIAL; AXILLARY DISSECTION; RADIOTHERAPY HYPOFRACTIONATION; UK STANDARDIZATION; CANCER; THERAPY; WOMEN; LUMPECTOMY; SURVIVAL; EXCISION AB Purpose: In patients with early-stage breast cancer treated with breast-conserving surgery, randomized trials have found little difference in local control and survival outcomes between patients treated with conventionally fractionated (CF-) whole breast irradiation (WBI) and those receiving hypofractionated (HF)-WBI. However, it remains controversial whether these results apply to all subgroups of patients. We therefore developed an evidence-based guideline to provide direction for clinical practice. Methods and Materials: A task force authorized by the American Society for Radiation Oncology weighed evidence from a systematic literature review and produced the recommendations contained herein. Results: The majority of patients in randomized trials were aged 50 years or older, had disease Stage pT1-2 pN0, did not receive chemotherapy, and were treated with a radiation dose homogeneity within +/- 7% in the central axis plane. Such patients experienced equivalent outcomes with either HF-WBI or CF-WBI. Patients not meeting these criteria were relatively underrepresented, and few of the trials reported subgroup analyses. For patients not receiving a radiation boost, the task force favored a dose schedule of 42.5 Gy in 16 fractions when HF-WBI is planned. The task force also recommended that the heart should be excluded from the primary treatment fields (when HF-WBI is used) due to lingering uncertainty regarding late effects of HF-WBI on cardiac function. The task force could not agree on the appropriateness of a tumor lied boost in patients treated with HF-WBI. Conclusion: Data were sufficient to support the use of HF-WBI for patients with early-stage breast cancer who met all the aforementioned criteria. For other patients. the task force could not reach agreement either for or against the use of HF-WBI, which nevertheless should not be interpreted as a contraindication to its use. Copyright (C) 2011 American Society for Radiation Oncology. Published by Elsevier Inc. C1 [Smith, Benjamin D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Bentzen, Soren M.] Univ Wisconsin, Dept Human Oncol, Sch Med & Publ Hlth, Madison, WI USA. [Correa, Candace R.; Pierce, Lori J.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Hahn, Carol A.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Hardenbergh, Patricia H.] Shaw Reg Canc Ctr, Vail, CO USA. [Ibbott, Geoffrey S.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [McCormick, Beryl; Powell, Simon N.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [McQueen, Julie R.] Duke Raleigh Canc Ctr, Durham, NC USA. [Recht, Abram] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Recht, Abram] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Vicini, Frank A.] Beaumont Canc Inst, Dept Radiat Oncol, Royal Oak, MI USA. [White, Julia R.] Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. [Haffty, Bruce G.] Canc Inst New Jersey, Dept Radiat Oncol, New Brunswick, NJ USA. RP Smith, BD (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM bsmith3@mdanderson.org RI Bentzen, Soren/E-3997-2012; White, Julia/J-6336-2014; OI Bentzen, Soren/0000-0002-7444-7564; Smith, Benjamin/0000-0001-7866-1093 NR 23 TC 134 Z9 139 U1 0 U2 9 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 SEP 1 PY 2011 VL 81 IS 1 BP 59 EP 68 DI 10.1016/j.ijrobp.2010.04.042 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 809YT UT WOS:000294093300009 PM 20638191 ER PT J AU Smith, ZA Gorgulho, AA Bezrukiy, N McArthur, D Agazaryan, N Selch, MT De Salles, AAF AF Smith, Zachary A. Gorgulho, Alessandra A. Bezrukiy, Nikita McArthur, David Agazaryan, Nzhde Selch, Michael T. De Salles, Antonio A. F. TI DEDICATED LINEAR ACCELERATOR RADIOSURGERY FOR TRIGEMINAL NEURALGIA: A SINGLE-CENTER EXPERIENCE IN 179 PATIENTS WITH VARIED DOSE PRESCRIPTIONS AND TREATMENT PLANS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Dedicated linear accelerator; Radiosurgery; Trigeminal neuralgia; Stereotactic ID GAMMA-KNIFE RADIOSURGERY; TERM-FOLLOW-UP; STEREOTACTIC RADIOSURGERY; MICROVASCULAR DECOMPRESSION; RHIZOTOMY; SURGERY; PAIN AB Purpose: Dedicated linear accelerator radiosurgery (D-LINAC) has become an important treatment for trigeminal neuralgia (TN). Although the use of gamma knife continues to he established, few large series exist using D-LINAC. The authors describe their results, comparing the effects of varied target and dose regimens. Methods and Materials: Between August 1995 and January 2008, 179 patients were treated with D-LINAC radiosurgery. Ten patients (5.58%) had no clinical follow-up. The median age was 74.0 years (range, 32-90 years). A total of 39 patients had secondary or atypical pain, and 130 had idiopathic TN. Initially. 28 patients received doses between 70 and 85 Gy, with the 30% isodose line (IDL) touching the brainstem. Then, using 90 Gy, 82 consecutive patients were treated with a 30% IDL and 59 patients with a 50% IDL tangential to the pons. Results: Of 169 patients, 134 (79.3%) experienced significant relief at a mean of 28.8 months (range, 5-142 months). Average time to relief was 1.92 months (range, immediate to 6 months). A total of 31 patients (19.0%) had recurrent pain at 13.5 months. Of 87 patients with idiopathic TN without prior procedures, 79 (90.8%) had initial relief. Among 28 patients treated with 70 Gy and 30% IDL, 18 patients (64.3%) had significant relief, and 10 (35.7%) had numbness. Of the patients with 90 Gy and 30% IDL at the brainstem, 59 (79.0%) had significant relief and 48.9% had numbness. Among 59 consecutive patients with similar dose but the 50% isodoseline at the brainstem, 49 patients (88.0%) had excellent/good relief. Numbness, averaging 2.49 on a subjective scale of 1 to 5, was experienced by 49.7% of the patients. Conclusions: Increased radiation close and volume of brainstem irradiation may improve clinical outcomes with the trade-off of trigeminal dysfunction. Further study of the implications of close and target are needed to optimize outcomes and to minimize complications. (C) 2011 Elsevier Inc. C1 [Smith, Zachary A.; Gorgulho, Alessandra A.; Bezrukiy, Nikita; McArthur, David; De Salles, Antonio A. F.] UCLA Med Ctr, Dept Neurosurg, Los Angeles, CA USA. [Agazaryan, Nzhde; Selch, Michael T.; De Salles, Antonio A. F.] UCLA Med Ctr, Dept Radiat Oncol, Los Angeles, CA USA. [De Salles, Antonio A. F.] W Los Angeles Vet Adm Hosp, Los Angeles, CA USA. RP De Salles, AAF (reprint author), Univ Calif Los Angeles, Dept Neurosurg, Ronald Reagan UCLA Med Ctr, Los Angeles, CA 90024 USA. EM adesalles@mednet.ucla.edu NR 36 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2011 VL 81 IS 1 BP 225 EP 231 DI 10.1016/j.ijrobp.2010.05.058 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 809YT UT WOS:000294093300031 PM 21236592 ER PT J AU Kahn, J Loeffler, JS Niemierko, A Chiocca, EA Batchelor, T Chakravarti, A AF Kahn, Jenna Loeffler, Jay Steven Niemierko, Andrzej Chiocca, E. Antonio Batchelor, Tracy Chakravarti, Arnab TI LONG-TERM OUTCOMES OF PATIENTS WITH SPINAL CORD GLIOMAS TREATED BY MODERN CONFORMAL RADIATION TECHNIQUES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Spinal cord glioma; Intramedullary tumor; Proton beam therapy; Radiation therapy ID POSTOPERATIVE RADIOTHERAPY; RETROSPECTIVE ANALYSIS; CONSERVATIVE SURGERY; SURGICAL RESECTION; EPENDYMOMAS; THERAPY; MANAGEMENT; TUMORS; ASTROCYTOMA AB Purpose: This study retrospectively examines the long-term therapeutic outcomes of 32 patients with primary spinal cord gliomas at Massachusetts General Hospital between 1991 and 2005 treated by either photon intensity-modulated radiotherapy or conformal proton radiotherapy. Methods and Materials: Individual patient tumor types included 14 ependymomas, 17 astrocytomas, and one oligodendroglioma. Twenty-two patients were treated with photon beam radiation therapy, and 10 patients were treated with proton beam therapy. The overall survival and time to progression were analyzed. Average radiation dose for patients was 51 Gy in 1.8 median daily fractions over 29 treatments. Results: For all 32 patients, the overall 5-year survival was 65% and the progression-free survival was 61%, respectively. Overall survival was significantly worse tor patients more than 55 years of age (p = 0.02). Ependymoma patients had significantly longer survival times than astrocytoma patients (p = 0.05). Patients who had undergone a biopsy developed worse outcomes then those with a resection (p = 0.05). With the caveat of a limited number of patients, the multivariate model seems to suggest improved overall survival for younger patients (<54 years of age), ependymoma histology, and photon vs. proton treatment. Conclusion: For patients with spinal cord gliomas, significant factors associated with patient outcome include tumor pathology, age, extent of surgery, and treatment. (C) 2011 Elsevier Inc. C1 [Chiocca, E. Antonio; Chakravarti, Arnab] Ohio State Univ, James Canc Hosp, Solove Res Inst, Med Ctr,Dept Neurol Surg, Columbus, OH 43210 USA. [Kahn, Jenna; Loeffler, Jay Steven; Niemierko, Andrzej] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Batchelor, Tracy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurooncol, Boston, MA USA. RP Chakravarti, A (reprint author), Ohio State Univ, Sch Med, Arthur G James Comprehens Canc Ctr, 300 W 10th Ave,Room 080B, Columbus, OH 43210 USA. EM arnab.chakravarti@osumc.edu FU Massachusetts General Hospital; National Institutes of Health/National Cancer Institute [R01CA108633, RC2CA148190]; Brain Tumor Funders Collaborative Group FX This study was supported by the Brian D. Silber funds, Massachusetts General Hospital (to J.L.) and National Institutes of Health/National Cancer Institute awards R01CA108633 (to A.C.): RC2CA148190 (to A.C.): and the Brain Tumor Funders Collaborative Group (to A.C.). NR 33 TC 5 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2011 VL 81 IS 1 BP 232 EP 238 DI 10.1016/j.ijrobp.2010.05.009 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 809YT UT WOS:000294093300032 PM 20947265 ER PT J AU Berbeco, RI Ngwa, W Makrigiorgos, GM AF Berbeco, Ross I. Ngwa, Wilfred Makrigiorgos, G. Mike TI LOCALIZED DOSE ENHANCEMENT TO TUMOR BLOOD VESSEL ENDOTHELIAL CELLS VIA MEGAVOLTAGE X-RAYS AND TARGETED GOLD NANOPARTICLES: NEW POTENTIAL FOR EXTERNAL BEAM RADIOTHERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Nanoparticles; Anti-angiogenesis; SBRT ID CANCER STEM-CELLS; PHOTON BEAMS; DRUG-DELIVERY; SOLID TUMORS; RADIATION; THERAPY; ANGIOGENESIS; BIODISTRIBUTION; MICROSPHERES; LIPOSOMES AB Purpose: Tumor endothelial cell damage during radiation therapy may contribute significantly to tumor eradication and treatment efficacy. Gold nanoparticles (AuNPs) delivered preferentially to the walls of tumor blood vessels produce low-energy, short-range photoelectrons during external beam radiotherapy, boosting dose to the tumor microvasculature. In this study dosimetry at the single-cell level is used to estimate the anticipated AuNP-mediated dose enhancement to tumor endothelial cells during 6-MV X-ray irradiation. Methods and Materials: Endothelial cells are modeled as thin slabs with 100-nm-diameter AuNPs attached within the blood vessel. The number of photoelectrons emitted per AuNP per gray of X-rays is computed at multiple points along the external beam central axis by use of a Monte Carlo-generated energy fluence spectrum. The energy deposited from AuNP emissions to the endothelium is calculated based on an analytic method incorporating the energy-loss formula of Cole. The endothelial dose enhancement factor (EDEF) is the ratio of the overall (externally plus internally generated) dose to endothelial cells in the presence of AuNPs to the dose without AuNPs (from the external beam only). Results: At 20-cm depth, the EDEF is 1.7 (70% dose increase) for an intravascular AuNP concentration of 30 mg/g. Most of this dose enhancement arises from the low-energy (approximately 100 keV) portion of the linear accelerator X-ray spectrum. Furthermore, for AuNP concentrations ranging from 7 to 140 mg/g, EDEF values of 1.2 to 4.4 (20-340% dose increase) are calculated. Conclusions: In contrast to calculations assuming that AuNPs distributed homogeneously throughout the target volume (macrodosimetry), our cellular microdosimetry calculations predict a major dose enhancement to tumor microvasculature from conventional linear accelerator X-rays. This effect may enable the delivery of ablative therapeutic doses to these sensitive microstructures while maintaining established dose constraints for the organs at risk. (C) 2011 Elsevier Inc. C1 [Berbeco, Ross I.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Berbeco, RI (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. EM rberbeco@partners.org NR 43 TC 60 Z9 63 U1 2 U2 16 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 SEP 1 PY 2011 VL 81 IS 1 BP 270 EP 276 DI 10.1016/j.ijrobp.2010.10.022 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 809YT UT WOS:000294093300037 PM 21163591 ER PT J AU Sumino, T Gadikota, HR Varadarajan, KM Kwon, YM Rubash, HE Li, GA AF Sumino, Takanobu Gadikota, Hemanth R. Varadarajan, Kartik M. Kwon, Young-Min Rubash, Harry E. Li, Guoan TI Do high flexion posterior stabilised total knee arthroplasty designs increase knee flexion? A meta analysis SO INTERNATIONAL ORTHOPAEDICS LA English DT Review ID FOLLOW-UP; OPTIMIZING FLEXION; DEEP FLEXION; MOTION; RANGE; KINEMATICS; REPLACEMENT; STANDARD; PROSTHESIS; IMPLANT AB This systematic literature review analysed the change in range of knee flexion from pre-operative values, following conventional posterior stabilised (PS) and high-flexion (H-F) PS total knee arthroplasty (TKA). We calculated the weighted mean differences of pre- and postoperative flexion using meta-analysis with random effect modelling. Eighteen studies met our inclusion criteria. These data included a total of 2,104 PS knees that received conventional implants and 518 knees that received H-F implants. The pooled gain in flexion was 4.70A degrees in the conventional group (p < 0.0001) and 4.81A degrees in the H-F group (p = 0.0008). In the subgroup analysis, the Western patient group showed significant difference in the gain of flexion with both implants. In contrast, no significant gain in flexion was observed in the Asian patient group. These results suggest that improvement of preoperative flexion after TKA using current H-F PS prostheses is similar to that of conventional PS prostheses. C1 [Sumino, Takanobu; Gadikota, Hemanth R.; Varadarajan, Kartik M.; Kwon, Young-Min; Rubash, Harry E.; Li, Guoan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. [Sumino, Takanobu] Nihon Univ, Sch Med, Dept Orthopaed Surg, Itabashi Ku, Tokyo 1738610, Japan. RP Li, GA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Bioengn Lab, 55 Fruit St, Boston, MA 02114 USA. EM gli1@partners.org NR 50 TC 19 Z9 20 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 J9 INT ORTHOP JI Int. Orthop. PD SEP PY 2011 VL 35 IS 9 BP 1309 EP 1319 DI 10.1007/s00264-011-1228-4 PG 11 WC Orthopedics SC Orthopedics GA 809OS UT WOS:000294067200007 PM 21409370 ER PT J AU Gadikota, HR Seon, JK Wu, JL Gill, TJ Li, GA AF Gadikota, Hemanth R. Seon, Jong Keun Wu, Jia-Lin Gill, Thomas J. Li, Guoan TI The effect of isolated popliteus tendon complex injury on graft force in anterior cruciate ligament reconstructed knees SO INTERNATIONAL ORTHOPAEDICS LA English DT Article ID POSTEROLATERAL ROTATORY INSTABILITY; POPLITEOFIBULAR LIGAMENT; POSTERIOR CRUCIATE; VIDEO ANALYSIS; MECHANISMS; LOADS; STABILITY; AVULSION; STRAIN AB Failure to diagnose injury to the posterolateral structures has been found to increase the forces experienced by the anterior cruciate ligament (ACL) and ACL grafts which may cause their subsequent failure. An isolated injury to the popliteus complex (PC) consisting of the popliteus tendon and popliteofibular ligament is not uncommon. Therefore, the purpose of this study was to discover if an isolated injury to the PC can significantly affect the forces experienced by the ACL graft under external loading conditions. We hypothesised that, under external tibial torque, the ACL graft will experience a significant increase in force, in knees with PC injury compared to the intact PC condition. Under varus tibial torque (10 N m), we observed minimal changes in the varus tibial rotation due to isolated sectioning of the PC in an ACL reconstructed knee (P > 0.05). Consequently, no significant increase in the ACL graft force was observed under varus tibial torque. In contrast, sectioning the PC resulted in a significant increase in the external tibial rotation compared to the intact PC knee condition under the external rotational tibial torque (5 N m) at all flexion angles (P < 0.05). These changes in kinematics under external tibial torque were manifested as elevated ACL graft forces at all selected flexion angles (P < 0.05). Prompt diagnosis of isolated PC injury and its treatment are warranted to prevent potential failure of ACL reconstruction. C1 [Gadikota, Hemanth R.; Seon, Jong Keun; Wu, Jia-Lin; Gill, Thomas J.; Li, Guoan] Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. [Gadikota, Hemanth R.; Seon, Jong Keun; Wu, Jia-Lin; Gill, Thomas J.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Seon, Jong Keun] Chonnam Natl Univ Hwasun Hosp, Dept Orthopaed, Jeonnam, South Korea. [Wu, Jia-Lin] Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Orthopaed Surg, Taipei, Taiwan. RP Li, GA (reprint author), Massachusetts Gen Hosp, Bioengn Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institutes of Health [R01AR055612]; Department of Orthopaedic Surgery of Massachusetts General Hospital FX We gratefully acknowledge the support of the National Institutes of Health (R01AR055612) and the Department of Orthopaedic Surgery of Massachusetts General Hospital. NR 31 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 J9 INT ORTHOP JI Int. Orthop. PD SEP PY 2011 VL 35 IS 9 BP 1403 EP 1408 DI 10.1007/s00264-010-1118-1 PG 6 WC Orthopedics SC Orthopedics GA 809OS UT WOS:000294067200019 PM 20835706 ER PT J AU Campbell, MK Tessaro, I Gellin, M Valle, CG Golden, S Kaye, L Ganz, PA McCabe, MS Jacobs, LA Syrjala, K Anderson, B Jones, AF Miller, K AF Campbell, Marci K. Tessaro, Irene Gellin, Mindy Valle, Carmina G. Golden, Shannon Kaye, Leanne Ganz, Patricia A. McCabe, Mary S. Jacobs, Linda A. Syrjala, Karen Anderson, Barbara Jones, Alison F. Miller, Kenneth TI Adult cancer survivorship care: experiences from the LIVESTRONG centers of excellence network SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Cancer; Cancer survivorship; Chronic care model; Health care ID CHRONIC ILLNESS CARE; QUALITY IMPROVEMENT; MODEL AB Background The objectives of this study were to characterize survivorship models of care across eight LIVESTRONG Survivorship Center of Excellence (COE) Network sites and to identify barriers and facilitators influencing survivorship care. Methods Using the framework of the Chronic Care Model (CCM), quantitative and qualitative methods of inquiry were conducted with the COEs. Methods included document reviews, key informant telephone interviews with 39 participants, online Assessment of Chronic Illness Care (ACIC) surveys with 40 participants, and three site visits. Results Several overarching themes emerged in qualitative interviews and were substantiated by quantitative methods. Health system factors supporting survivorship care include organization and leadership commitment and program champions at various levels of the health care team. System barriers include reimbursement issues, lack of space, and the need for leadership commitment to support changes in clinical practices as well as having program "champions" among clinical staff. Multiple models of care include separate survivorship clinics and integrated models as well as consultative models. COEs' scores on the ACIC survey showed overall "reasonable support" for survivorship care; however, the clinical information system domain was least developed. Although the ACIC findings indicated "reasonable support" for self-management, the qualitative analysis revealed that self-management support was largely limited to health promotion provided in clinic-based education and counseling sessions, with few COEs providing patients with self-management tools and interventions. Conclusions The CCM framework captured experiences and challenges of these COEs and provided insight into the current state of survivorship care in the context of National Cancer Institute-designated comprehensive cancer centers. Findings showed that cancer patients and providers could benefit from clinical information systems that would better identify candidates for survivorship care and provide timely information. In addition, a crucial area for development is self-management support outside of clinical care. Implications for cancer survivors Cancer survivors may benefit from learning about the experience and challenges faced by the eight LIVESTRONG Centers of Excellence in developing programs and models for cancer survivorship care, and these findings may inform patient and caregiver efforts to seek, evaluate, and advocate for quality survivorship programs designed to meet their needs. C1 [Campbell, Marci K.; Valle, Carmina G.; Kaye, Leanne] Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Campbell, Marci K.; Valle, Carmina G.; Kaye, Leanne] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. [Campbell, Marci K.; Tessaro, Irene; Gellin, Mindy; Valle, Carmina G.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Golden, Shannon] Goldsmith Res Grp, Winston Salem, NC USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [McCabe, Mary S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Jacobs, Linda A.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Syrjala, Karen] Fred Hutchinson Canc Res Ctr, Biobehav Sci Dept, Seattle, WA 98104 USA. [Anderson, Barbara] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Jones, Alison F.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Miller, Kenneth] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Campbell, MK (reprint author), Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, CB 7461,1700 Martin Luther King Blvd,Room 316, Chapel Hill, NC 27599 USA. EM campbel7@email.unc.edu FU LIVESTRONG Foundation; V (Jim Valvano) Foundation FX The authors would like to acknowledge contributions of the following individuals: Caroline Huffman, RN; K. Scott Baker, MD; and Donald Rosenstein, MD. This research was supported by funding from the LIVESTRONG Foundation and the V (Jim Valvano) Foundation. NR 20 TC 29 Z9 30 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD SEP PY 2011 VL 5 IS 3 BP 271 EP 282 DI 10.1007/s11764-011-0180-z PG 12 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA 811AV UT WOS:000294174700007 PM 21553353 ER PT J AU Snyder, CF Frick, KD Herbert, RJ Blackford, AL Neville, BA Carducci, MA Earle, CC AF Snyder, Claire F. Frick, Kevin D. Herbert, Robert J. Blackford, Amanda L. Neville, Bridget A. Carducci, Michael A. Earle, Craig C. TI Preventive care in prostate cancer patients: following diagnosis and for five-year survivors SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Prostate cancer; Preventive care; Survivorship ID COLORECTAL-CANCER; HEALTH MAINTENANCE; COMORBIDITY INDEX AB Introduction Prostate cancer is the most common male cancer. Survival rates are high, making preventive care maintenance important. Factors associated with prostate-cancer cases' preventive care in the short-term (Year 1) and long-term (Year 5), and how survivors' care compares to non-cancer controls, require study. Methods This retrospective, controlled SEER-Medicare study included loco-regional prostate cancer cases age >= 66 in fee-for-service Medicare diagnosed in 2000 and surviving >= 12 months, and non-cancer controls matched to cases on socio-demographics and survival. Outcomes included influenza vaccination, cholesterol screening, and colorectal cancer screening. Independent variables were number of physician visits, physician specialties visited, initial prostate cancer treatment, socio-demographic characteristics, and case-control status. Results There were 13,507 cases and 13,507 controls in Year 1, and 10,482 cases and 10,482 controls in Year 5. In Years 1 and 5, total number of visits (6/6 outcomes) and primary care provider (PCP) visits (5/6 outcomes) were most consistently associated with preventive care receipt. In Year 1, prostate cancer cases were more likely than controls to receive influenza vaccination (48% vs. 45%) but less likely to receive colorectal cancer screening (29% vs. 31%) (both p < 0.0001). In Year 5, prostate cancer cases remained more likely than controls to receive influenza vaccination (46% vs. 44%; p < 0.0001). Conclusions Differences in survivors' short-term preventive care did not lead to worse long-term preventive care. The number of physician visits, particularly PCP visits, are important factors associated with appropriate care. Implications for Cancer Survivors PCP involvement in prostate cancer patients' care is critical both during treatment and for long-term survivors. C1 [Snyder, Claire F.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. [Snyder, Claire F.; Blackford, Amanda L.; Carducci, Michael A.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. [Snyder, Claire F.; Frick, Kevin D.; Herbert, Robert J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Neville, Bridget A.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Earle, Craig C.] Inst Clin Evaluat Sci, Toronto, ON, Canada. RP Snyder, CF (reprint author), 624 N Broadway,Room 657, Baltimore, MD 21205 USA. EM csnyder@jhsph.edu FU Johns Hopkins Bloomberg School of Public Health; American Cancer Society [MRSG-08-011-01-CPPB]; National Cancer Institute Center [5P30CA006973] FX This research was funded through the Ho Ching Yang Memorial Faculty Fellowship Award from the Johns Hopkins Bloomberg School of Public Health. Drs. Snyder and Carducci are also supported by a Mentored Research Scholar Grant from the American Cancer Society (MRSG-08-011-01-CPPB). Dr. Carducci is also supported by a National Cancer Institute Center Grant (5P30CA006973). NR 19 TC 25 Z9 25 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD SEP PY 2011 VL 5 IS 3 BP 283 EP 291 DI 10.1007/s11764-011-0181-y PG 9 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA 811AV UT WOS:000294174700008 PM 21553320 ER PT J AU Hill, JM Vernig, PM Lee, JK Brown, C Orsillo, SM AF Hill, Justin M. Vernig, Peter M. Lee, Jonathan K. Brown, Cynthia Orsillo, Susan M. TI The Development of a Brief Acceptance and Mindfulness-Based Program Aimed at Reducing Sexual Revictimization Among College Women With a History of Childhood Sexual Abuse SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID BEHAVIORAL COUPLE THERAPY; COMMITMENT THERAPY; EXPERIENTIAL AVOIDANCE; MEDIATING VARIABLES; PREVENTION PROGRAM; COGNITIVE THERAPY; ANXIETY DISORDER; RISK-FACTORS; ADULT WOMEN; ASSAULT AB Women with a history of childhood sexual assault (CSA) are more likely to be revictimized; however, most existing programs aimed at reducing sexual victimization do not expressly address the issue of revictimization. The present study examined the efficacy of a brief mindfulness-based program in reducing rates of sexual assault and revictimization in college women over the course of an academic semester. Although the results were not statistically significant, a large-magnitude effect was noted, whereby women with a history of CSA who participated in the program were less likely to be sexually assaulted and raped at 2-month follow-up. (C) 2011 Wiley Periodicals, Inc. J Clin Psychol 67: 969-980, 2011. C1 [Hill, Justin M.] Boston VA Healthcare Syst, Dept Psychol, Boston, MA 02130 USA. [Vernig, Peter M.; Lee, Jonathan K.; Brown, Cynthia; Orsillo, Susan M.] Suffolk Univ, Boston, MA USA. RP Hill, JM (reprint author), Boston VA Healthcare Syst, Dept Psychol, 150 S Huntington Ave, Boston, MA 02130 USA. EM justin.hill2@va.gov NR 59 TC 6 Z9 6 U1 6 U2 25 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD SEP PY 2011 VL 67 IS 9 BP 969 EP 980 DI 10.1002/jclp.20813 PG 12 WC Psychology, Clinical SC Psychology GA 811WN UT WOS:000294248200011 PM 21544818 ER PT J AU Yoon, MK Sharma, A Corbo, J McCulley, TJ AF Yoon, Michael K. Sharma, Aseem Corbo, Joseph McCulley, Timothy J. TI Progressive Aphasia and Vision Loss in a Teen-Aged Girl SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Editorial Material ID TUMEFACTIVE DEMYELINATING LESIONS; MYELINOCLASTIC DIFFUSE SCLEROSIS; MAGNETIC-RESONANCE SPECTROSCOPY; PROTON MR SPECTROSCOPY; MULTIPLE-SCLEROSIS; IMAGING SIGN; OPEN-RING; BRAIN; TUMOR; HEMIPARESIS C1 [McCulley, Timothy J.] Johns Hopkins Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21287 USA. [Yoon, Michael K.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA USA. [Yoon, Michael K.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Sharma, Aseem] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Corbo, Joseph] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. [Corbo, Joseph] Washington Univ, Sch Med, Dept Immunol, St Louis, MO 63110 USA. [McCulley, Timothy J.] King Khalid Eye Specialist Hosp, Riyadh, Saudi Arabia. RP McCulley, TJ (reprint author), Johns Hopkins Sch Med, Wilmer Eye Inst, Dept Ophthalmol, 600 N Wolfe St,Wilmer 110, Baltimore, MD 21287 USA. EM tmccull5@jhmi.edu OI Corbo, Joseph/0000-0002-9323-7140 FU NEI NIH HHS [R01 EY018826] NR 35 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2011 VL 31 IS 3 BP 279 EP 284 DI 10.1097/WNO.0b013e31822a94f9 PG 6 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 811IX UT WOS:000294203200019 PM 21857191 ER PT J AU Sharaf, B Jandali-Rifai, M Susarla, SM Dodson, TB AF Sharaf, Basel Jandali-Rifai, Maher Susarla, Srinivas M. Dodson, Thomas B. TI Do Perioperative Antibiotics Decrease Implant Failure? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; DENTAL IMPLANTS; PROPHYLACTIC ANTIBIOTICS; SURGERY; PLACEMENT; SURVIVAL; SUCCESS AB Purpose: To execute an evidence-based review answering the following question: "Among patients receiving dental implants, do those who receive perioperative antibiotic therapy, compared with those who do not, have a decreased likelihood of implant failure?" Materials and Methods: We performed a literature review. The primary predictor variable was an antibiotic regimen, which was grouped into 3 categories: a single preoperative dose, a single preoperative dose and multiday postoperative therapy, and no antibiotic therapy. The primary and secondary outcome variables were implant failure and postoperative infection, respectively. Results: Eight studies meeting the inclusion criteria were reviewed. Two studies assessed the effect of a single preoperative antibiotic dose and reported a reduction in implant failure by 1.3% to 2% compared with no antibiotics use. Two studies compared the effect of pre- and postoperative antibiotics and no antibiotic use and found a 4.2% decrease to 1.1% increase in the failure rates when antibiotics were used. Four studies considered the effect of different antibiotic regimens. Only 2 studies found a statistically significant reduction in implant failure (2.5% to 5.4%) when a single preoperative antibiotic dose was used in conjunction with multiday treatment, compared with postoperative multiday treatment only. Four studies analyzed the rate of postoperative infection, which was 0.6% to 3% when no antibiotics were used, 0.6% when preoperative antibiotics alone were used, and 0.8% to 1% when preoperative and postoperative antibiotics were given. Conclusion: A single dose of preoperative antibiotic therapy may slightly decrease the failure rate of dental implants. However, the current data do not support the routine use of postoperative antibiotics, which can be tailored by the clinician to the patient's specific needs. (C) 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:2345-2350, 2011 C1 [Sharaf, Basel] Albert Einstein Coll Med, Div Plast & Reconstruct Surg, Bronx, NY 10467 USA. [Jandali-Rifai, Maher] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Dept Oral & Maxillofacial Surg, New York, NY USA. [Susarla, Srinivas M.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02115 USA. RP Sharaf, B (reprint author), Albert Einstein Coll Med, Div Plast & Reconstruct Surg, 3353 Bainbridge Ave, Bronx, NY 10467 USA. EM sharafddsmd@gmail.com OI Susarla, Srinivas/0000-0003-0155-8260 NR 16 TC 18 Z9 21 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2011 VL 69 IS 9 BP 2345 EP 2350 DI 10.1016/j.joms.2011.02.095 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 810WV UT WOS:000294160600017 PM 21676512 ER PT J AU Granowski-LeCornu, M Chuang, SK Kaban, LB August, M AF Granowski-LeCornu, Megan Chuang, Sung-Kiang Kaban, Leonard B. August, Meredith TI Osteosarcoma of the Jaws: Factors Influencing Prognosis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID OSTEOGENIC-SARCOMA; ADJUVANT CHEMOTHERAPY; SINGLE INSTITUTION; FOLLOW-UP; EXPERIENCE; NECK; HEAD; OUTCOMES; BONES AB Purpose: To evaluate patient, tumor, and treatment variables associated with survival in patients with jaw osteosarcoma (JOS) and to compare survival in patients treated before 1991 with those managed with more aggressive treatment protocols since 1992. Patients and Methods: This is a retrospective cohort study of patients with JOS treated at Massachusetts General Hospital from 1967 through 2007. Patients were divided by treatment date into Group 1, 1967 to 1991 (n = 30) and Group 2, 1992 to 2009 (n = 17). Medical records were reviewed to collect the following: demographic, radiographic, tumor-specific, treatment, and survival data. The 2 subgroups were statistically compared. Results: There were 47 patients (32 males, 15 females) with a mean age of 30.9 years (range 4 to 74). Mandibular location showed a trend toward improved survival (P = .06). Average tumor size was 4.38 cm (range 0.5 to 9.0 cm). Larger tumors were associated with decreased overall survival (P = .016). Higher grade tumors had decreased overall survival (P = .01). Clear surgical margins were obtained in 67% of patients. Clear surgical margins correlated with improved survival (P = .002). Maxillary JOS constituted 83% of those with positive margins. Overall, 5-year survival was 68%. Improved 5-year survival was noted in group 2 (77%) compared with group 1 (52%) [P = .0073]. Patients who developed secondary osteosarcomas (n = 10) had 4.5-fold increased risk of death (P = .01). Recurrence was associated with 7-fold increased risk of death (P = .0008). Thirteen patients died of JOS. Conclusions: Improved survival was noted in treatment group 2. This group benefited from improved imaging, earlier diagnosis and more aggressive treatment that included improved surgical clearance. A clear survival advantage for neoadjuvant chemotherapy was not demonstrated. (C) 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:2368-2375, 2011 C1 [August, Meredith] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Granowski-LeCornu, Megan] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP August, M (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02114 USA. EM maugust@partners.org FU Harvard Medical School Office of Enrichment Student Research; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery FX This study was funded in part by Harvard Medical School Office of Enrichment Student Research, Grant and the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund. NR 22 TC 10 Z9 10 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2011 VL 69 IS 9 BP 2368 EP 2375 DI 10.1016/j.joms.2010.10.023 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 810WV UT WOS:000294160600020 PM 21288615 ER PT J AU Camp, ER Findlay, VJ Vaena, SG Walsh, J Lewin, DN Turner, DP Watson, DK AF Camp, E. Ramsay Findlay, Victoria J. Vaena, Silvia G. Walsh, Jarret Lewin, David N. Turner, David P. Watson, Dennis K. TI ASSOCIATION FOR ACADEMIC SURGERY Slug Expression Enhances Tumor Formation in a Noninvasive Rectal Cancer Model SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE colorectal cancer; e-cadherin; slug; rectal tumor model ID EPITHELIAL-MESENCHYMAL TRANSITIONS; TRANSCRIPTION FACTOR SNAIL; LYMPH-NODE METASTASIS; CELL-LINES; COLORECTAL-CANCER; RESISTANCE; CARCINOMA; DISEASE; GROWTH; MICE AB Background. Epithelial-to-mesenchymal transition (EMT) is a series of molecular changes allowing epithelial cancer cells to acquire properties of mesenchymal cells: increased motility, invasion, and protection from apoptosis. Transcriptional regulators such as Slug mediate EMT, working in part to repress E-cadherin transcription. We report a novel, noninvasive in vivo rectal cancer model to explore the role of Slug in colorectal cancer (CRC) tumor development. Methods. For the generation of DLD-1 cells overexpressing Slug (Slug DLD-1), a Slug or empty (Empty DLD-1) pCMV-3Tag-1 (kanamycin-resistant) vector was used for transfection. Cells were evaluated for Slug and E-cadherin expression, and cell migration and invasion. For the in vivo study, colon cancer cells (parental DLD-1, Slug DLD-1, empty DLD-1, and HCT-116) were submucosally injected into the posterior rectum of nude mice using endoscopic guidance. After 28 d, tumors were harvested and tissue was analyzed. Results. Slug expression in our panel of colon cancer cell lines was inversely correlated with E-cadherin expression and enhanced migration/invasion. Slug DLD-1 cells demonstrated a 21-fold increased Slug and 19-fold decreased E-cadherin expression compared with empty DLD-1. Similarly, the Slug DLD-1 cells had significantly enhanced cellular migration and invasion. In the orthotopic rectal cancer model, Slug DLD-1 cells formed rectal tumors in 9/10 (90%) of the mice (mean volume = 458 mm(3)) compared with only 1/10 (10%) with empty DLD-1 cells. Conclusion. Slug mediates EMT with enhanced in vivo rectal tumor formation. Our noninvasive in vivo model enables researchers to explore the molecular consequences of altered genes in a clinically relevant rectal cancer in an effort to develop novel therapeutic approaches for patients with rectal cancer. Published by Elsevier Inc. C1 [Camp, E. Ramsay; Vaena, Silvia G.; Walsh, Jarret] Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. [Findlay, Victoria J.; Lewin, David N.; Turner, David P.; Watson, Dennis K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Watson, Dennis K.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Findlay, Victoria J.; Turner, David P.; Watson, Dennis K.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Camp, E. Ramsay] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Camp, ER (reprint author), Med Univ S Carolina, Dept Surg, 25 Courtenay Dr,Room 7018,MSC 295, Charleston, SC 29425 USA. EM campe@musc.edu FU Hollings Cancer Center; American Cancer Society; Institutional Research Grant; National Institutes of Health [1K08CA142904] FX The authors acknowledge supported in part for this work by Hollings Cancer Center Translational Research Award 2008, American Cancer Society, Institutional Research Grant 2009, and the National Institutes of Health, 1K08CA142904 (ERC). NR 20 TC 11 Z9 11 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD SEP PY 2011 VL 170 IS 1 BP 56 EP 63 DI 10.1016/j.jss.2011.02.012 PG 8 WC Surgery SC Surgery GA 804BD UT WOS:000293627800036 PM 21470622 ER PT J AU Deschler, DG Emerick, KS Lin, DT Bunting, GW AF Deschler, Daniel G. Emerick, Kevin S. Lin, Derrick T. Bunting, Glenn W. TI Simplified Technique of Tracheoesophageal Prosthesis Placement at the Time of Secondary Tracheoesophageal Puncture (TEP) SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Combined Sections Meeting of the Triological-Society CY JAN 27-30, 2011 CL Scottsdale, AZ SP Triol Soc DE Tracheoesophageal prosthesis placement; tracheoesophageal puncture ID VOICE PROSTHESIS; TOTAL LARYNGECTOMY; BLOM-SINGER; RESTORATION AB Objectives: Secondary tracheoesophageal (TE) puncture standardly involves placement of a catheter at time of TE fistula creation. We explore the feasibility of placement of the prosthesis at the time of TE puncture (TEP) obviating the need for a subsequent procedure to place the prosthesis. We describe the technique and evaluate the success and potential advantages. Study Design: Retrospective chart review of consecutive patients who underwent TE prosthesis placement at the time of secondary TEP from 3/2009 to 1/2011. Methods: Fourteen patients underwent the primary TE prosthesis placement at the time of secondary puncture and were evaluated. Assessed outcomes included patient demographics, success of prosthesis placement, need for repeat procedure, early or late prosthesis dislodgement, complications, and specific voice outcomes. Results: Patient cohort included nine males, five females, with average age of 64 years. All TE prosthesis placements were successful. The 12-mm 20 F Blom-Singer Indwelling prosthesis was used in all cases. No complications occurred during prosthesis placement. Two perioperative complications occurred: one case of transient pulmonary edema from general anesthesia, one case of posterior tracheal wall swelling. The second was addressed with placement of a larger prosthesis. All patients successfully achieved good voice at an average of 4 days after the procedure (range: 1-9 days). Conclusions: This initial series of 14 consecutive patients demonstrates successful TE prosthesis placement at the time of secondary TE puncture. Functional voice was achieved in all patients with no significant immediate complications. No dislodgements occurred and no repeat procedures were required. Voice acquisition was achieved at an earlier time (4 days on average) than with traditional techniques and without the necessity of a subsequent procedure. Primary prosthesis placement at the time of secondary TE puncture is a successful option for surgical voice restoration with distinct advantages and minimal complications. C1 [Deschler, Daniel G.; Emerick, Kevin S.; Lin, Derrick T.; Bunting, Glenn W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Div Head & Neck Surg, Dept Otol & Laryngol,Med Sch, Boston, MA 02420 USA. RP Deschler, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Div Head & Neck Surg, Dept Otol & Laryngol,Med Sch, Boston, MA 02420 USA. EM daniel_deschler@meei.harvard.edu NR 12 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2011 VL 121 IS 9 BP 1855 EP 1859 DI 10.1002/lary.21910 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 811OD UT WOS:000294219900008 PM 21692076 ER PT J AU Sun, JY Tseng, HY Xu, L Hunter, Z Ciccarelli, B Fulciniti, M Zhu, BM Maghsoudi, K Yang, G Gong, P Zhou, YS Liu, X Munshi, NC Patterson, CJ Treon, SP AF Sun, Jenny Y. Tseng, Hsiuyi Xu, Lian Hunter, Zachary Ciccarelli, Bryan Fulciniti, Mariateresa Zhu, Bangmin Maghsoudi, Kaveh Yang, Guang Gong, Ping Zhou, Yangsheng Liu, Xia Munshi, Nikhil C. Patterson, Christopher J. Treon, Steven P. TI Vorinostat induced cellular stress disrupts the p38 mitogen activated protein kinase and extracellular signal regulated kinase pathways leading to apoptosis in Waldenstrom macroglobulinemia cells SO LEUKEMIA & LYMPHOMA LA English DT Article DE Lymphoma and Hodgkin disease; lymphocytes; cell lines and animal models; chemotherapeutic approaches ID HISTONE-DEACETYLASE INHIBITORS; SUBEROYLANILIDE HYDROXAMIC ACID; SYNERGISTIC INDUCTION; MULTIPLE-MYELOMA; LEUKEMIA-CELLS; BORTEZOMIB; DIFFERENTIATION; HIAP2; XIAP; SAHA AB Histone deacetylases (HDACs) are aberrantly expressed, and inhibitors of HDACs induce apoptosis in lymphoplasmacytic cells (LPCs) in Waldenstrom macroglobulinemia (WM). The molecular profile by which these agents induce apoptosis in WM LPCs remains to be delineated. We examined the activity of the histone deacetylase inhibitor, vorinostat, and dissected its pro-apoptotic pathways in WM LPCs. Vorinostat induced apoptosis in WM cells through activating specific caspases at varying times. Inhibitors of apoptosis (IAPs) were down-regulated after vorinostat treatment. Cellular stress induced in vorinostat-treated WM cells was reflected by changes in the mitogen activated protein kinase (MAPK) pathways. Activated phospho-p38 MAPK was up-regulated at 12 h, while phospho-extracellular signal-regulated kinase (Erk) abruptly decreased at 24 h. Bortezomib did not augment vorinostat induced primary WM cell killing as reported in other B-cell disorders. These studies support that stress induced apoptosis in vorinostat-treated WM LPCs is mediated through disrupting the activity of the Erk and p38 MAPK pathways. C1 [Yang, Guang; Zhou, Yangsheng; Treon, Steven P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Maghsoudi, Kaveh] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Munshi, Nikhil C.] Boston VA Healthcare Syst, Boston, MA USA. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 FU International Waldenstrom's Macroglobulinemia Foundation; Bing Fund for Waldenstrom's Macroglobulinemia; Bailey Family Fund for Waldenstrom's Research; Linda and Edward Nelson Fund for Waldenstrom's Macroglobulinemia FX This study is supported by the International Waldenstrom's Macroglobulinemia Foundation, the Bing Fund for Waldenstrom's Macroglobulinemia, the Bailey Family Fund for Waldenstrom's Research, and the Linda and Edward Nelson Fund for Waldenstrom's Macroglobulinemia. NR 48 TC 4 Z9 4 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP PY 2011 VL 52 IS 9 BP 1777 EP 1786 DI 10.3109/10428194.2011.577850 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 811QM UT WOS:000294228100024 PM 21657958 ER PT J AU Sarma, MK Huda, A Nagarajan, R Hinkin, CH Wilson, N Gupta, RK Frias-Martinez, E Sayre, J Guze, B Han, SH Thomas, MA AF Sarma, Manoj K. Huda, Amir Nagarajan, Rajakumar Hinkin, Charles H. Wilson, Neil Gupta, Rakesh K. Frias-Martinez, Enrique Sayre, James Guze, Barry Han, Steven-Huy Thomas, M. Albert TI Multi-dimensional MR spectroscopy: towards a better understanding of hepatic encephalopathy SO METABOLIC BRAIN DISEASE LA English DT Article DE MRS; COSY; Hepatic encephalopathy; Glutamine; Glutamate; Neuropsychological tests ID MAGNETIC-RESONANCE-SPECTROSCOPY; ACUTE LIVER-FAILURE; CIRRHOTIC-PATIENTS; H-1-NMR SPECTROSCOPY; IN-VIVO; NEUROPSYCHOLOGICAL CHARACTERIZATION; OVERT ENCEPHALOPATHY; GLUCOSE-METABOLISM; CEREBRAL AMMONIA; WORKING PARTY AB Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests. The goals of this study were to quantify cerebral metabolites, separate glutamate (Glu) from glutamine (Gln) in patients with minimal hepatic encephalopathy (MHE) as well as healthy subjects using the prior-knowledge fitting (ProFit) algorithm on data acquired by two-dimensional (2D) localized correlated spectroscopy (L-COSY) on two different MR scanners, and to correlate the metabolite changes with neuropsychological (NP) tests. We studied 14 MHE patients and 18 healthy controls using a GE 1.5 T Signa MR scanner. Another group of 16 MHE patients and 18 healthy controls were studied using a Siemens 1.5 T Avanto MR scanner. The following parameters were used for L-COSY: TR/TE = 2 s/30 ms, 3 x 3 x 3 cm(3) voxel size, 96 Delta t(1) increments with 8 averages per Delta t(1). Using the ProFit algorithm, we were able to differentiate Gln from Glu on the GE 1.5 T data in the medial frontal white/gray matter. The ratios of myo-inositol (mI), Glu, total choline, scyllo-inositol (sI), phosphoethanolamine (PE), and total N-acetyl aspartate (NAA) showed statistically significant decline in HE patients compared to healthy controls, while the ratio of Gln was significantly increased. Similar trend was seen in the ProFit quantified Siemens 1.5 T data in the frontal and occipito-parietal white/gray regions. Among the NP domain scores, motor function, cognitive speed, executive function and the global scores showed significant differences. Excellent correlations between various NP domains and metabolite ratios were also observed. ProFit based cerebral metabolite quantitation enhances the understanding and basis of the current hypothesis of MHE. C1 [Sarma, Manoj K.; Huda, Amir; Nagarajan, Rajakumar; Wilson, Neil; Frias-Martinez, Enrique; Sayre, James; Thomas, M. Albert] Univ Calif Los Angeles, Dept Radiol Sci, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Huda, Amir] Calif State Univ Fresno, Dept Phys, Fresno, CA 93740 USA. [Hinkin, Charles H.; Guze, Barry; Thomas, M. Albert] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. [Hinkin, Charles H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gupta, Rakesh K.] Sanjay Gandhi Postgrad Inst Med Sci, Dept Radiol, Lucknow, Uttar Pradesh, India. [Han, Steven-Huy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Hepatol, Los Angeles, CA 90095 USA. RP Thomas, MA (reprint author), Univ Calif Los Angeles, Dept Radiol Sci, David Geffen Sch Med, CHS BL 428,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM athomas@mednet.ucla.edu RI Thomas, m. albert/A-6176-2012; Nagarajan, Rajakumar/A-7179-2013; Huda, Amir/I-5987-2015; Sarma, Manoj/J-8299-2014 OI Huda, Amir/0000-0002-0171-3796; FU National Institute of Mental Health (NIMH) [1R01MH06569501A1] FX This research was supported by a National Institute of Mental Health (NIMH) RO1 grant (1R01MH06569501A1). Scientific support of Drs. Nader Binesh, Kenneth Yue, Shida Banakar, and Sherry Liu during the earlier phase of this project is gratefully acknowledged. Authors acknowledge the support of Dr. Rolf Schulte, Prof. Dr. Peter Boesiger and his group members at ETH-Zurich, Switzerland in sharing the earlier version of the ProFit algorithm for processing the localized 2D J-resolved spectrum. NR 76 TC 17 Z9 18 U1 2 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD SEP PY 2011 VL 26 IS 3 BP 173 EP 184 DI 10.1007/s11011-011-9250-1 PG 12 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 811QK UT WOS:000294227800003 PM 21698453 ER PT J AU Sienkiewicz, E Magkos, F Aronis, KN Brinkoetter, M Chamberland, JP Chou, S Arampatzi, KM Gao, CY Koniaris, A Mantzoros, CS AF Sienkiewicz, Elizabeth Magkos, Faidon Aronis, Konstantinos N. Brinkoetter, Mary Chamberland, John P. Chou, Sharon Arampatzi, Kalliopi M. Gao, Chuanyun Koniaris, Anastasia Mantzoros, Christos S. TI Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID FUNCTIONAL HYPOTHALAMIC AMENORRHEA; RECOMBINANT HUMAN LEPTIN; REPLACEMENT THERAPY; CELL-PROLIFERATION; ANOREXIA-NERVOSA; GROWTH-FACTOR; DOUBLE-BLIND; OB/OB MICE; MASS; OSTEOPOROSIS AB Strenuously exercising young women with hypothalamic amenorrhea are hypoleptinemic and have low bone mineral density (BMD) and content (BMC), which predispose them to increased fracture risk. Short-term leptin replacement in these women corrects many neuroendocrine abnormalities and increases circulating levels of bone formation markers. Whether treatment with recombinant methionyl human leptin (metreleptin) for a long period improves BMD and BMC remains unknown. We studied 20 strenuously exercising young women with hypoleptinemia (leptin concentration <5 ng/mL) and hypothalamic amenorrhea of at least 6 months' duration. Eleven were randomized to metreleptin (initial dose, 0.08 mg/[kg.d] for 3 months; altered thereafter to 0.12 mg/kg for lack of efficacy or 0.04 mg/[kg.d] for more than 5% weight loss) and 9 were randomized to placebo for 9 months. After a 3-month washout period, subjects were reexamined at the 1-year time point. Six subjects elected to continue on open-label metreleptin treatment for another 12 months. Two subjects dropped out after 18 months, and 4 completed the entire 2-year study. The BMD and BMC of the total body, lumbar spine (L1-L4), hip, and radius were assessed by using dual-energy x-ray absorptiometry at baseline and at 3, 6, 9, 12, 18, and 24 months of treatment. Metabolic and hormonal parameters and bone markers were measured in blood and urine. Metreleptin significantly increased BMC (P = .034) and tended to increase BMD (P = .069) at the lumbar spine at 9 months in the entire study group (intention-to-treat analysis). In subjects who completed the entire 2-year study (n = 4), metreleptin significantly increased BMD (P = .024) and BMC (P = .049) at the lumbar spine by 4% to 6%. Changes were not significant at the whole body, hip, and radius. Changes in hormonal and metabolic parameters and bone markers were moderate during the first year of treatment, but metreleptin further increased insulin-like growth factor 1 and decreased cortisol and crosslinked C-terminal telopeptide of type 1 collagen concentrations in serum during the second year of treatment (P < .05). The incremental area under the estradiol concentration curve over the 2-year course of the study correlated positively with the corresponding increase in lumbar spine BMD (rho = 0.42, P = .039). Long-term metreleptin administration in strenuously exercising young women with hypothalamic amenorrhea and hypoleptinemia increases lumbar spine BMD and BMC and alters bone remodeling milieu to favor bone accretion. Results from this pilot study should be confirmed by future, larger clinical trials and need to be extended by studying bone microarchitecture and fracture risk. Published by Elsevier Inc. C1 [Sienkiewicz, Elizabeth; Magkos, Faidon; Aronis, Konstantinos N.; Brinkoetter, Mary; Chamberland, John P.; Chou, Sharon; Arampatzi, Kalliopi M.; Gao, Chuanyun; Koniaris, Anastasia; Mantzoros, Christos S.] Harvard Univ, Sch Med, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Chamberland, John P.; Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Med, Div Endocrinol Diabet & Metab, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012; Aronis, Konstantinos/J-6582-2014; OI Aronis, Konstantinos/0000-0001-7189-8434; Chamberland, John/0000-0002-7862-1371 FU National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913, AG032030]; National Institutes of Health-National Center for Research Resources [M01-RR-01032] FX The Mantzoros group is supported by National Institute of Diabetes and Digestive and Kidney Diseases grants 58785, 79929, and 81913 and AG032030. Funding was also received from the National Institutes of Health-National Center for Research Resources grant M01-RR-01032 (Harvard Clinical and Translational Science Center). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Amylin Pharmaceuticals supplied recombinant human leptin for this study and approved the design of the study, but had no role in study design; conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 54 TC 67 Z9 67 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2011 VL 60 IS 9 BP 1211 EP 1221 DI 10.1016/j.metabol.2011.05.016 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 811FT UT WOS:000294192000003 PM 21741057 ER PT J AU Kim, SM Cho, GJ Yannakoulia, M Hwang, TG Kim, IH Park, EK Mantzoros, CS AF Kim, Seon Mee Cho, Geum Joo Yannakoulia, Mary Hwang, Taik Gun Kim, In Hee Park, Eun Kyung Mantzoros, Christos S. TI Lifestyle modification increases circulating adiponectin concentrations but does not change vaspin concentrations SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID VISCERAL ADIPOSE-TISSUE; HIGH-MOLECULAR-WEIGHT; METABOLIC SYNDROME; INSULIN SENSITIVITY; RANDOMIZED-TRIAL; DIABETIC WOMEN; SERUM-LEVELS; OBESITY; INTERVENTION; RISK AB The objective of the study was to evaluate the effects of a 10-month lifestyle intervention on the components of the metabolic syndrome (MetSyn) in Koreans with MetSyn as well as on blood concentrations of adiponectin and vaspin. One hundred thirty-eight patients with MetSyn, recruited from a community health care center, were consecutively enrolled in the study; 12 patients dropped of the intervention, leaving 126 subjects (76 men and 50 women; age, 65.3 +/- 9.0 years). All participants followed a 10-month lifestyle modification interventional program, including dietary counseling, advice on increasing physical activity, and recommendations to stop or limit smoking and alcohol drinking. Anthropometric and biochemical parameters related to the components of the MetSyn, including blood concentrations of adiponectin and vaspin, were assessed pre- and postintervention. At baseline, adiponectin concentrations were moderately negatively correlated to insulin concentrations and insulin resistance evaluated by the homeostasis model assessment. In response to lifestyle modification, statistically significant changes were found in systolic and diastolic blood pressure, total cholesterol, triglyceride, and insulin concentrations, as well as in homeostasis model assessment of insulin resistance. Adiponectin concentrations postintervention, compared with the preintervention levels, increased (7.2 +/- 4.0 vs 6.8 +/- 3.9 mu g/mL, respectively; P < .05), whereas vaspin concentrations remained unchanged (0.25 +/- 0.19 vs 0.26 +/- 0.20 ng/mL, respectively; P = .64). A 10-month lifestyle modification program in Korean patients with MetSyn led to favorable changes in metabolic parameters and adiponectin but not vaspin concentrations. (C) 2011 Elsevier Inc. All rights reserved. C1 [Kim, Seon Mee] Korea Univ, Dept Family Med, Coll Med, Seoul 152703, South Korea. [Kim, Seon Mee; Yannakoulia, Mary; Mantzoros, Christos S.] Harvard Univ, Sch Med, Div Endocrinol Diabet & Metab, Dept Med,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Cho, Geum Joo; Hwang, Taik Gun; Kim, In Hee; Park, Eun Kyung] Guro Gu Publ Hlth Ctr, Seoul 152055, South Korea. [Yannakoulia, Mary] Harokopio Univ, Dept Nutr & Dietet, Athens 11743, Greece. [Mantzoros, Christos S.] Harvard Univ, Sch Med, Endocrinol Sect, Boston VA Healthcare Syst, Boston, MA 02130 USA. RP Kim, SM (reprint author), Korea Univ, Dept Family Med, Sch Med, Seoul 152050, South Korea. EM ksmpdh@korea.ac.kr; myiannak@hua.gr FU Korean Seoul City Research and Business Development Program [10526]; Fulbright Foundation in Greece; Beth Israel Deaconess Medical Center; National Institute of Diabetes and Digestive and Kidney Diseases [DK 58785, DK 79929, DK 81913] FX This study was supported by a grant (10526) from the Korean Seoul City Research and Business Development Program (SM Kim). The academic sabbatical of M Yannakoulia in the Mantzoros Laboratory has been supported by the Fulbright Foundation in Greece. This study was also supported by a discretionary grant from Beth Israel Deaconess Medical Center and National Institute of Diabetes and Digestive and Kidney Diseases grants DK 58785, DK 79929, and DK 81913 (CS Mantzoros). NR 47 TC 18 Z9 18 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2011 VL 60 IS 9 BP 1294 EP 1299 DI 10.1016/j.metabol.2011.01.013 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 811FT UT WOS:000294192000013 PM 21489569 ER PT J AU Srikantan, S Abdelmohsen, K Lee, EK Tominaga, K Subaran, SS Kuwano, Y Kulshrestha, R Panchakshari, R Kim, HH Yang, XL Martindale, JL Marasa, BS Kim, MM Wersto, RP Indig, FE Chowdhury, D Gorospe, M AF Srikantan, Subramanya Abdelmohsen, Kotb Lee, Eun Kyung Tominaga, Kumiko Subaran, Sarah S. Kuwano, Yuki Kulshrestha, Ritu Panchakshari, Rohit Kim, Hyeon Ho Yang, Xiaoling Martindale, Jennifer L. Marasa, Bernard S. Kim, Mihee M. Wersto, Robert P. Indig, Fred E. Chowdhury, Dipanjan Gorospe, Myriam TI Translational Control of TOP2A Influences Doxorubicin Efficacy SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA TOPOISOMERASE-II; RNA-BINDING PROTEINS; CANCER-CHEMOTHERAPY; ANIMAL DEVELOPMENT; MAMMALIAN-CELLS; HUR; EXPRESSION; REPRESSION; STRESS; PHOSPHORYLATION AB The cellular abundance of topoisomerase II alpha (TOP2A) critically maintains DNA topology after replication and determines the efficacy of TOP2 inhibitors in chemotherapy. Here, we report that the RNA-binding protein HuR, commonly overexpressed in cancers, binds to the TOP2A 3'-untranslated region (3'UTR) and increases TOP2A translation. Reducing HuR levels triggered the recruitment of TOP2A transcripts to RNA-induced silencing complex (RISC) components and to cytoplasmic processing bodies. Using a novel MS2-tagged RNA precipitation method, we identified microRNA miR-548c-3p as a mediator of these effects and further uncovered that the interaction of miR-548c-3p with the TOP2A 3'UTR repressed TOP2A translation by antagonizing the action of HuR. Lowering TOP2A by silencing HuR or by overexpressing miR-548c-3p selectively decreased DNA damage after treatment with the chemotherapeutic agent doxorubicin. In sum, HuR enhances TOP2A translation by competing with miR-548c-3p; their combined actions control TOP2A expression levels and determine the effectiveness of doxorubicin. C1 [Srikantan, Subramanya; Abdelmohsen, Kotb; Lee, Eun Kyung; Tominaga, Kumiko; Kuwano, Yuki; Kim, Hyeon Ho; Yang, Xiaoling; Martindale, Jennifer L.; Marasa, Bernard S.; Kim, Mihee M.; Gorospe, Myriam] NIA, LMBI, IRP, NIH, Baltimore, MD 21224 USA. [Subaran, Sarah S.; Wersto, Robert P.; Indig, Fred E.] NIA, Res Resources Branch, IRP, NIH, Baltimore, MD 21224 USA. [Subaran, Sarah S.; Kulshrestha, Ritu; Panchakshari, Rohit; Chowdhury, Dipanjan] Harvard Univ, Dana Farber Canc Inst, Dept Radiat Oncol, Sch Med, Boston, MA 02118 USA. [Kim, Hyeon Ho] Sungkyunkwan Univ, Samsung Biomed Res Inst, Sch Med, Seoul, South Korea. RP Gorospe, M (reprint author), NIA, LMBI, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM Dipanjan_Chowdhury@dfci.harvard.edu; myriam-gorospe@nih.gov OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810 FU NIA-IRP, NIH; Barr Award; NCI [R01CA142698] FX This research was supported by the NIA-IRP, NIH. R. K., R. P., and D. C. were supported by the Barr Award and NCI R01CA142698. NR 39 TC 46 Z9 48 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2011 VL 31 IS 18 BP 3790 EP 3801 DI 10.1128/MCB.05639-11 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 811WE UT WOS:000294246700011 PM 21768308 ER PT J AU Tamayo, AG Slater, L Taylor-Parker, J Bharti, A Harrison, R Hung, DT Murphy, JR AF Tamayo, Alfred G. Slater, Louise Taylor-Parker, Julian Bharti, Ajit Harrison, Robert Hung, Deborah T. Murphy, John R. TI GRP78(BiP) facilitates the cytosolic delivery of anthrax lethal factor (LF) in vivo and functions as an unfoldase in vitro SO MOLECULAR MICROBIOLOGY LA English DT Article ID HEPTAMERIC PROTECTIVE ANTIGEN; HEAT-SHOCK PROTEINS; ENDOPLASMIC-RETICULUM; TOXIN RECEPTOR; PORE FORMATION; MOLECULAR CHAPERONES; BINDING-PROTEIN; CELLS; TRANSLOCATION; COMPLEX AB Anthrax toxin is an A/B bacterial protein toxin which is composed of the enzymatically active Lethal Factor (LF) and/or Oedema Factor (EF) bound to Protective Antigen 63 (PA63) which functions as both the receptor binding and transmembrane domains. Once the toxin binds to its cell surface receptors it is internalized into the cell and traffics through Rab5- and Rab7-associated endosomal vesicles. Following acidification of the vesicle lumen, PA63 undergoes a dynamic change forming a beta-barrel that inserts into and forms a pore through the endosomal membrane. It is widely recognized that LF, and the related fusion protein LFnDTA, must be completely denatured in order to transit through the PA63 formed pore and enter the eukaryotic cell cytosol. We demonstrate by protease protection assays that the molecular chaperone GRP78 mediates the unfolding of LFnDTA and LF at neutral pH and thereby converts these proteins from a trypsin resistant to sensitive conformation. We have used immunoelectron microscopy and gold-labelled antibodies to demonstrate that both GRP78 and GRP94 chaperones are present in the lumen of endosomal vesicles. Finally, we have used siRNA to demonstrate that knock-down of GRP78 results in the emergence of resistance to anthrax lethal toxin and oedema toxin action. C1 [Tamayo, Alfred G.; Taylor-Parker, Julian; Bharti, Ajit; Harrison, Robert; Murphy, John R.] Boston Univ, Sch Med, Dept Med, Sect Mol Med, Boston, MA 02118 USA. [Slater, Louise; Hung, Deborah T.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Slater, Louise; Hung, Deborah T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Murphy, JR (reprint author), Boston Univ, Sch Med, Dept Med, Sect Mol Med, Boston, MA 02118 USA. EM jrmrphy@bu.edu OI Tamayo, Alfred/0000-0002-2321-0831 FU National Institute of Allergy and Infectious Diseases [AI-021628]; National Institute of Allergy and Infectious Disease Regional Center of Excellence [AI-057159] FX We thank Dr Maria Ericsson, Harvard Medical School, for performing the transmission electron microscopy. This work was supported by Public Health Service grant AI-021628 from the National Institute of Allergy and Infectious Diseases (J.R.M.) and by National Institute of Allergy and Infectious Disease Regional Center of Excellence grant AI-057159 (J.R.M., D.T.H.). NR 44 TC 11 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2011 VL 81 IS 5 BP 1390 EP 1401 DI 10.1111/j.1365-2958.2011.07770.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 811MC UT WOS:000294214100020 PM 21797942 ER PT J AU Ruderfer, DM Kirov, G Chambert, K Moran, JL Owen, MJ O'Donovan, MC Sklar, P Purcell, SM AF Ruderfer, D. M. Kirov, G. Chambert, K. Moran, J. L. Owen, M. J. O'Donovan, M. C. Sklar, P. Purcell, S. M. TI A family-based study of common polygenic variation and risk of schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Letter ID HUMAN HEIGHT; LOCI C1 [Ruderfer, D. M.; Sklar, P.; Purcell, S. M.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Ruderfer, D. M.; Sklar, P.; Purcell, S. M.] Harvard Univ, Sch Med, Boston, MA USA. [Ruderfer, D. M.; Sklar, P.; Purcell, S. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ruderfer, D. M.; Chambert, K.; Moran, J. L.; Sklar, P.; Purcell, S. M.] 7 Cambridge Ctr, Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Kirov, G.; Owen, M. J.; O'Donovan, M. C.] Cardiff Univ, Sch Med, Dept Psychol Med & Neurol, MRC Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales. RP Ruderfer, DM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. EM shaun@pngu.mgh.harvard.edu RI turton, miranda/F-4682-2011; Ruderfer, Douglas/M-5795-2016; OI Ruderfer, Douglas/0000-0002-2365-386X; O'Donovan, Michael/0000-0001-7073-2379; Moran, Jennifer/0000-0002-5664-4716 FU Medical Research Council [G0800509]; NHGRI NIH HHS [R01 HG005827] NR 8 TC 18 Z9 18 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2011 VL 16 IS 9 BP 887 EP 888 DI 10.1038/mp.2011.34 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 811VX UT WOS:000294245600003 PM 21483432 ER PT J AU Michor, F Liphardt, J Ferrari, M Widom, J AF Michor, Franziska Liphardt, Jan Ferrari, Mauro Widom, Jonathan TI What does physics have to do with cancer? SO NATURE REVIEWS CANCER LA English DT Review ID ENCODED NUCLEOSOME ORGANIZATION; MESOPOROUS SILICON PARTICLES; CHRONIC MYELOID-LEUKEMIA; DNA-FORMING SEQUENCES; DRUG-RESISTANCE; CHROMATIN-STRUCTURE; IN-VIVO; G4 DNA; COMBINATION CHEMOTHERAPY; PANCREATIC-CANCER AB Large-scale cancer genomics, proteomics and RNA-sequencing efforts are currently mapping in fine detail the genetic and biochemical alterations that occur in cancer. However, it is becoming clear that it is difficult to integrate and interpret these data and to translate them into treatments. This difficulty is compounded by the recognition that cancer cells evolve, and that initiation, progression and metastasis are influenced by a wide variety of factors. To help tackle this challenge, the US National Cancer Institute Physical Sciences-Oncology Centers initiative is bringing together physicists, cancer biologists, chemists, mathematicians and engineers. How are we beginning to address cancer from the perspective of the physical sciences? C1 [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Liphardt, Jan] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA. [Liphardt, Jan] Univ Calif Berkeley, Div Cell & Dev Biol, Berkeley, CA 94720 USA. [Ferrari, Mauro] Methodist Hosp Res Inst, Houston, TX 77030 USA. [Widom, Jonathan] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA. [Widom, Jonathan] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA. RP Michor, F (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM michor@jimmy.harvard.edu RI Liphardt, Jan/A-5906-2012; OI Liphardt, Jan/0000-0003-2835-5025 FU US National Cancer Institute Physical Sciences-Oncology Center (PSOC) initiative; Bay Area PSOC; Methodist Hospital Research Institute PSOC; Northwestern University PSOC; DoD/BCRP [W81XWH-09-1-0212]; Ernest Cockrell Jr. Distinguished Endowed Chair FX The authors would like to acknowledge support from the US National Cancer Institute Physical Sciences-Oncology Center (PSOC) initiative to fund the Dana-Farber Cancer Institute PSOC (F.M.), Bay Area PSOC (J.L.), The Methodist Hospital Research Institute PSOC (M.F.) and the Northwestern University PSOC (J.W.). M.F.'s research for this article was furthermore supported by grants from DoD/BCRP (W81XWH-09-1-0212), as well as by the Ernest Cockrell Jr. Distinguished Endowed Chair. The authors would like to thank A. Sebeson for her invaluable help. This work is dedicated to Professor Jonathan Widom. With his passing, we have lost both a major intellectual force and a valued member of our community, as well as a trusted friend and colleague. NR 146 TC 70 Z9 71 U1 7 U2 68 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD SEP PY 2011 VL 11 IS 9 BP 657 EP 670 DI 10.1038/nrc3092 PG 14 WC Oncology SC Oncology GA 811IZ UT WOS:000294203400013 PM 21850037 ER PT J AU Bianchi, MT Clark, AG Fisher, JL AF Bianchi, Matt T. Clark, Alison G. Fisher, Janet L. TI The wake-promoting transmitter histamine preferentially enhances alpha-4 subunit-containing GABA(A) receptors SO NEUROPHARMACOLOGY LA English DT Article DE Sleep; Wake; Extrasynaptic; Modulation ID TEMPORAL-LOBE EPILEPSY; GATED ION CHANNELS; TONIC INHIBITION; GRANULE CELLS; TUBEROMAMMILLARY NUCLEUS; HISTIDINE-DECARBOXYLASE; NEURONAL EXCITABILITY; HIPPOCAMPAL-NEURONS; THALAMIC NEURONS; NERVOUS-SYSTEM AB Histamine is an important wake-promoting neurotransmitter that activates seven-transmembrane G-protein coupled histamine receptors. However, histamine demonstrates target promiscuity, including direct interaction with the structurally unrelated glutamate (NMDA) and GABA(A) receptor channels. Previous work showed that histamine enhances the activity of recombinant GABA(A) receptor isoforms typically found in synaptic locations, although co-release of histamine and GABA is not known to occur in vivo. Here we used patch clamp recordings of various recombinant GABA(A) receptor isoforms (alpha 1-6, beta 1-3, gamma 1-3, delta) to test the hypothesis that histamine might show subunit preference under low GABA concentration (extrasynaptic) conditions. We found that histamine potentiated the whole-cell responses to GABA for all tested subunit combinations. However, the magnitude of enhancement was largest (similar to 400% of EC10 GABA-evoked currents) with alpha 4 beta 3 and alpha 4 beta 3X isoforms, where X could be gamma or delta. In contrast, histamine (1 mM) had small effects on prolonging deactivation of alpha 4 beta 3 gamma 2 receptors following brief (5 ms) pulses of 1 mM GABA. These findings suggest GABA-histamine cross-talk may occur preferentially at low GABA concentrations, which could theoretically be inhibitory (via enhancing tonic inhibition), directly excitatory (via enhancing presynaptic GABAergic signaling), or indirectly excitatory (via inhibiting GABAergic interneurons). (C) 2011 Elsevier Ltd. All rights reserved. C1 [Clark, Alison G.; Fisher, Janet L.] Univ S Carolina, Sch Med, Dept Pharmacol Physiol & Neurosci, Columbia, SC 29208 USA. [Bianchi, Matt T.] Massachusetts Gen Hosp, Steep Div, Dept Neurol, Boston, MA 02114 USA. RP Fisher, JL (reprint author), Univ S Carolina, Sch Med, Dept Pharmacol Physiol & Neurosci, Columbia, SC 29208 USA. EM jfisher@uscmed.sc.edu FU NIH-NINDS [RO1-NS045950]; University of South Carolina School of Medicine FX This work was supported by NIH-NINDS (RO1-NS045950) and the University of South Carolina School of Medicine summer research program. NR 70 TC 7 Z9 7 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 EI 1873-7064 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2011 VL 61 IS 4 BP 747 EP 752 DI 10.1016/j.neuropharm.2011.05.020 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 809XN UT WOS:000294090100024 PM 21640733 ER PT J AU Hoh, BL Nathoo, S Chi, YY Mocco, J Barker, FG AF Hoh, Brian L. Nathoo, Sunina Chi, Yueh-Yun Mocco, J. Barker, Fred G., II TI Incidence of Seizures or Epilepsy After Clipping or Coiling of Ruptured and Unruptured Cerebral Aneurysms in the Nationwide Inpatient Sample Database: 2002-2007 SO NEUROSURGERY LA English DT Article DE Aneurysm; Clipping; Coiling; Epilepsy; Seizures; Subarachnoid hemorrhage ID SUBARACHNOID HEMORRHAGE; INTRACRANIAL ANEURYSMS; ENDOVASCULAR TREATMENT; ANTICONVULSANT PROPHYLAXIS; UNITED-STATES; HOSPITAL MORTALITY; EMBOLIZATION; VOLUME; OCCLUSION; SURGERY AB BACKGROUND: It is not clear whether treatment modality (clipping or coiling) affects the risk of seizures after treatment for cerebral aneurysms. OBJECTIVE: To determine whether there is an increased risk of seizures after clipping vs coiling. METHODS: Hospitalizations for clipping or coiling of ruptured and unruptured aneurysms were identified in the Nationwide Inpatient Sample Database for 2002 to 2007 by International Classification of Diseases 9th Revision codes for subarachnoid hemorrhage or unruptured cerebral aneurysm and codes for clipping or coiling. Clipping and coiling were compared for the combined primary endpoint of seizures or epilepsy. The analysis was adjusted for patient-specific and hospital-specific factors using generalized linear models with generalized estimated equations. RESULTS: There were 10 899 hospitalizations for ruptured aneurysms (6593 clipping, 4306 coiling), and 9686 hospitalizations for unruptured aneurysms (4483 clipping, 5203 coiling). For ruptured aneurysm patients, clipping had a similar incidence of seizures or epilepsy compared with coiling (10.7% vs 11.1%, respectively, adjusted odds ratio: 0.596; 95% confidence interval: 0.158-2.248; P = .445 after adjustment for patient-specific and hospital-specific factors). For unruptured aneurysm patients, clipping was associated with a significantly higher risk of seizures or epilepsy (9.2%) compared with coiling (6.2%) (adjusted odds ratio: 1.362; 95% confidence interval: 0.155-1.606; P < .001 after adjustment for patient-specific and hospital-specific factors). Seizures or epilepsy were significantly associated with longer hospitalizations (P,. 01) and higher hospital charges (P < .0001), except in coiled unruptured aneurysm patients, in which seizures or epilepsy were not significantly associated with hospital charges (P = .31). CONCLUSION: In unruptured cerebral aneurysm patients, clipping is associated with a higher risk of seizures or epilepsy. C1 [Hoh, Brian L.; Nathoo, Sunina; Mocco, J.] Univ Florida, Dept Neurosurg, Gainesville, FL USA. [Chi, Yueh-Yun] Univ Florida, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA. [Barker, Fred G., II] Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Hoh, BL (reprint author), POB 100265, Gainesville, FL 32610 USA. EM brian.hoh@neurosurgery.ufl.edu OI Nathoo, Sunina/0000-0003-1182-0779 FU Codman Neurovasc FX Dr Hoh has received an honorarium from Codman Neurovascular. Dr Mocco received an unrestricted educational grant from Codman Neurovasc and is a consultant to Actelion Pharmaceuticals, Nfocus, and Lazarus Effect. The other authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 43 TC 27 Z9 28 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD SEP PY 2011 VL 69 IS 3 BP 644 EP 650 DI 10.1227/NEU.0b013e31821bc46d PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 803MU UT WOS:000293586200025 PM 21499155 ER PT J AU Babu, MA Nahed, BV DeMoya, MA Curry, WT AF Babu, Maya A. Nahed, Brian V. DeMoya, Marc A. Curry, William T. TI Is Trauma Transfer Influenced by Factors Other Than Medical Need? An Examination of Insurance Status and Transfer in Patients With Mild Head Injury SO NEUROSURGERY LA English DT Article DE Head trauma; Hospital transfer; Insurance status ID LEVEL-I; HOSPITAL MORTALITY; INTENSIVE-CARE; BRAIN-INJURY; CENTERS; ADMISSION; SYSTEM; SERVICES; WEEKEND; SURGERY AB BACKGROUND: The Emergency Medical Treatment and Active Labor Act was meant to provide access to emergency medical care irrespective of financial resources. Yet, many Level I trauma Centers have raised concerns about the financial drivers influencing transfer. OBJECTIVE: To study the relationship between insurance status and transfer, we focused on patients with mild head injury to tease apart the medical necessity for transfer from other potential drivers, such as financial factors. METHODS: Using the 2002 to 2006 American College of Surgeons National Trauma Databank and Massachusetts General Hospital's Trauma Databank from 1993 to 2009, we conducted a retrospective study and limited our population to patients with mild head injuries and mild to moderate systemic injuries as determined by the Glasgow Coma Scale, Abbreviated Injury Scale, or Injury Severity Score. Statistical analyses were conducted with STATA software. RESULTS: In a nationalized database, (1) uninsured patients with mild head injury are more likely to be transferred out of a Level II or III facility (adjusted odds ratio [OR]: 2.07; P = .000) compared with privately insured patients and (2) uninsured patients are less likely to be accepted by a Level II or III facility for transfer compared with privately insured patients (adjusted OR: = .143; P = .000l). For transfers received by 1 Level I trauma center (Massachusetts General Hospital), uninsured patients are more likely to be transferred to (1) Massachusetts General Hospital between midnight and 6 AM (adjusted OR: 5.201; P = .000) compared with other time periods throughout the day and (2) Massachusetts General Hospital on Sunday (adjusted OR: 1.09; P = .000) compared with other days of the week. CONCLUSION: Insurance status appears to influence transfer patterns. C1 [Babu, Maya A.] Mayo Clin, Dept Neurol Surg, Rochester, MN 55905 USA. [Nahed, Brian V.; Curry, William T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [DeMoya, Marc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Trauma Surg & Crit Care, Boston, MA USA. RP Babu, MA (reprint author), Mayo Clin, Dept Neurol Surg, 200 1st St SW, Rochester, MN 55905 USA. EM babu.maya@mayo.edu FU Council of State Neurosurgical Societies/Congress of Neurological Surgeons; Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics at Harvard Law School FX The authors received funding provided through the following grants: (1) 2009 to 2010 Council of State Neurosurgical Societies/Congress of Neurological Surgeons Medical Student Fellowship in Socioeconomic Research (2) 2009 to 2010 Student Fellowship from the Petrie-Flom Center for Health Law Policy, Biotechnology and Bioethics at Harvard Law School. The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 45 TC 25 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD SEP PY 2011 VL 69 IS 3 BP 659 EP 667 DI 10.1227/NEU.0b013e31821bc667 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 803MU UT WOS:000293586200029 PM 21499151 ER PT J AU Janakiraman, V Lazar, J Joynt, KE Jha, AK AF Janakiraman, Vanitha Lazar, Jane Joynt, Karen E. Jha, Ashish K. TI Hospital Volume, Provider Volume, and Complications After Childbirth in US Hospitals SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID UNITED-STATES; CESAREAN DELIVERY; LABOR; MANAGEMENT; MORBIDITY; MORTALITY; OUTCOMES; TRIAL; RATES; CARE AB OBJECTIVE: To examine the relationship between both hospital and provider case volume and obstetric complication rates in U.S. hospitals. METHODS: This was a nationwide retrospective cohort study of women admitted to acute care U.S. hospitals for childbirth in 2007. We examined four categories of maternal complications (lacerations, hemorrhage, infections, and thromboses) and created a composite measure. We examined the relationship of hospital volume, provider volume, and odds of complications. RESULTS: We found no consistent relationship between hospital volume and rates of maternal complications. In contrast, we found that women cared for by providers in the lowest quartile of provider volume (fewer than seven deliveries per year) had a 50% higher odds of complications compared with women cared for by obstetricians in the highest quartile (odds ratio 1.5, 95% confidence interval, 1.3-1.7, P < .001). Each of the individual complications occurred more frequently among the lowest-volume providers compared with others. Models that adjusted for hospital characteristics and cesarean delivery rate had only modest effects. CONCLUSION: Individual providers with a low volume of deliveries have greater maternal complication rates than providers with a high volume. If volume is causally related to lower complication rates, strategies for improving care for women during childbirth may include selective referral to higher-volume providers or additional training for low-volume providers to ensure better outcomes. C1 [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu NR 21 TC 31 Z9 31 U1 2 U2 6 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 SEP PY 2011 VL 118 IS 3 BP 521 EP 527 DI 10.1097/AOG.0b013e31822a65e4 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 810VP UT WOS:000294156200005 PM 21826039 ER PT J AU Baumler, P Irnich, D Linde, K Schneider, A Lewith, G Napadow, V Pfab, F Cummings, M Karst, M Han, JS Michalsen, A Berger, P Usichenko, T Lundeberg, T Lund, I Trinh, K Audette, JF Backer, M Dobos, G Joos, S Scott, M Banzer, W Musial, F Witt, CM Brinkhaus, B AF Baeumler, Petra Irnich, Dominik Linde, Klaus Schneider, Antonius Lewith, George Napadow, Vitaly Pfab, Florian Cummings, Mike Karst, Matthias Han, Ji-Sheng Michalsen, Andreas Berger, Phyllis Usichenko, Taras Lundeberg, Thomas Lund, Irene Trinh, Kien Audette, Joseph F. Baecker, Markus Dobos, Gustav Joos, Stefanie Scott, Mist Banzer, Winfried Musial, Frauke Witt, Claudia M. Brinkhaus, Benno TI Comment on Ernst et al. Acupuncture: Does it alleviate pain and are there serious risks? A review of reviews. [Pain 2011;152:755-764] SO PAIN LA English DT Letter C1 [Baeumler, Petra; Irnich, Dominik] Univ Munich, Ctr Multidisciplinary Pain, Dept Anaesthesiol, Munich, Germany. [Linde, Klaus; Schneider, Antonius] Tech Univ Munich, Inst Gen Practice, Munich, Germany. [Lewith, George] Aldermoor Hlth Ctr, Complementary Med Res Unit, Southampton, Hants, England. [Napadow, Vitaly; Pfab, Florian] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Charlestown, MA USA. [Cummings, Mike] BMAS, London, England. [Karst, Matthias] Hannover Med Sch, Pain Clin, Dept Anesthesiol, D-3000 Hannover, Germany. [Han, Ji-Sheng] Peking Univ, Neurosci Res Inst, Beijing 100871, Peoples R China. [Michalsen, Andreas] Immanuel Hosp Berlin, Dept Internal & Complementary Med, Berlin, Germany. [Usichenko, Taras] Ernst Moritz Arndt Univ Greifswald, Dept Anesthesiol & Intens Care Med, Greifswald, Germany. [Lundeberg, Thomas] Sabbatsbergs Hosp, Fdn Acupuncture & Alternat Biol Treatment Methods, S-11382 Stockholm, Sweden. [Lund, Irene] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. [Trinh, Kien] McMaster Univ, Off MD Admiss, Hamilton, ON, Canada. [Audette, Joseph F.] Harvard Univ, Sch Med, Boston, MA USA. [Baecker, Markus; Dobos, Gustav] Dept Internal & Integrat Med, Essen, Germany. [Joos, Stefanie] Univ Heidelberg Hosp, Dept Gen Practice & Hlth Serv Res, Heidelberg, Germany. [Scott, Mist] Oregon Hlth & Sci Univ, Sch Nursing, Fibromyalgia Res Grp, Arthrit & Rheumat Dis Dept,Sch Med, Portland, OR 97201 USA. [Banzer, Winfried] Goethe Univ Frankfurt, Dept Sports Sci, Frankfurt, Germany. [Musial, Frauke] Univ Tromso, Natl Res Ctr Complementary & Alternat Med NAFKAM, Dept Community Med, Fac Hlth Sci, Tromso, Norway. [Witt, Claudia M.; Brinkhaus, Benno] Charite Univ Med Ctr, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany. RP Irnich, D (reprint author), Univ Munich, Ctr Multidisciplinary Pain, Dept Anaesthesiol, Munich, Germany. EM Dominik.Irnich@med.uni-muenchen.de NR 7 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 2011 VL 152 IS 9 BP 2181 EP 2182 DI 10.1016/j.pain.2011.05.012 PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 810GF UT WOS:000294113100037 PM 21778019 ER PT J AU Tidey, JW Rohsenow, DJ Kaplan, GB Swift, RM Reid, N AF Tidey, Jennifer W. Rohsenow, Damaris J. Kaplan, Gary B. Swift, Robert M. Reid, Netesha TI Effects of contingency management and bupropion on cigarette smoking in smokers with schizophrenia SO PSYCHOPHARMACOLOGY LA English DT Article DE Tobacco dependence; Nicotine; Psychiatric comorbidity; Dual diagnosis; Smoking cessation; Incentives; Craving ID PLACEBO-CONTROLLED TRIAL; VOUCHER-BASED INCENTIVES; CARBON-MONOXIDE LEVELS; MONETARY REINFORCEMENT; CESSATION MEDICATIONS; NICOTINE REPLACEMENT; FAGERSTROM-TEST; DOUBLE-BLIND; DEPENDENCE; ABSTINENCE AB Individuals with schizophrenia have high smoking-related morbidity and mortality rates and need powerful and innovative smoking cessation interventions. This proof-of-concept study investigated the feasibility and initial efficacy of combining a contingency management intervention with bupropion to reduce smoking in people with schizophrenia. Using a double-blind, placebo-controlled, between-groups design, 57 non-treatment-seeking participants were randomized to receive 300 mg/day bupropion or placebo. One week later, participants were randomized to a contingency management (CM) intervention in which reductions in urinary cotinine levels were reinforced, or a non-contingent reinforcement (NR) condition in which session attendance was reinforced, regardless of cotinine level. Over the 22-day study period, participants visited the laboratory approximately three times per week to provide urine samples for analysis of cotinine levels, to give breath samples for analysis of carbon monoxide (CO) levels, and to report number of cigarettes smoked per day, nicotine withdrawal symptoms, cigarette craving, and psychiatric symptoms. Cotinine and CO levels significantly decreased during the study period in participants randomized to the CM condition, but not the NR condition. Bupropion did not reduce cotinine levels or increase the efficacy of CM. Cigarette craving and psychiatric symptom levels significantly decreased during the study in all groups. The results of this study indicate the efficacy and feasibility of this CM intervention for reducing smoking in individuals with schizophrenia. C1 [Tidey, Jennifer W.; Rohsenow, Damaris J.; Kaplan, Gary B.; Swift, Robert M.; Reid, Netesha] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Rohsenow, Damaris J.; Swift, Robert M.] Providence VA Med Ctr, Providence, RI USA. [Kaplan, Gary B.] VA Boston Healthcare Syst, Boston, MA USA. RP Tidey, JW (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box S-121-5, Providence, RI 02912 USA. EM Jennifer_Tidey@brown.edu FU NIH [R01-DA17566]; Department of Veterans Affairs FX This work was funded by NIH grant R01-DA17566 to the first author and a Senior Research Career Scientist Award from the Department of Veterans Affairs to the second author. This study was conducted at the Providence Veterans Affairs Medical Center and the Brown University Center for Alcohol and Addiction Studies, Providence, RI, USA. Portions of these data were presented at annual meetings of the College on Problems of Drug Dependence and the Society for Research on Nicotine and Tobacco. The authors thank Laura Dionne for her assistance with data management, Mihir Parikh, Elizabeth Cathers, and Amy Adolfo Signore for assistance with data collection, and the individuals who participated in this study for their contributions. NR 61 TC 25 Z9 25 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2011 VL 217 IS 2 BP 279 EP 287 DI 10.1007/s00213-011-2282-8 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 811PM UT WOS:000294224800012 PM 21475970 ER PT J AU Bello, I Steffen, JJ Hayashi, K AF Bello, Iruma Steffen, John J. Hayashi, Kentaro TI Cognitive motivational systems and life satisfaction in serious and persistent mental illness SO QUALITY OF LIFE RESEARCH LA English DT Article DE Severe mental illness; Quality of life; Behavioral activation; Behavioral inhibition ID QUALITY-OF-LIFE; BEHAVIORAL ACTIVATION; SCHIZOAFFECTIVE DISORDER; BIS/BAS SCALES; SCHIZOPHRENIA; INHIBITION; PERSONALITY; OUTPATIENTS; RECOVERY; ANXIETY AB Purpose Levels of life satisfaction are commonly used to measure attainment of recovery in serious and persistent mental illness (SPMI). There is some controversy about what constitutes life satisfaction and its measurement. This study explored the influence of cognitive motivational systems upon estimations of life satisfaction using structural equation modeling (SEM). Methods One hundred and ninety participants diagnosed with SPMI from Hawai'i's public mental health system completed instruments measuring cognitive motivational systems (e.g., behavioral activation and inhibition), psychological distress, and life satisfaction (e.g., quality of life and subjective well-being). Results Exploratory models indicated that higher behavioral inhibition or psychological distress predicts lower levels of life satisfaction. However, higher levels of behavioral activation predict higher levels of life satisfaction. There was no support for psychological distress as a mediator between cognitive motivational systems and life satisfaction. Conclusions Overall, cognitive motivational systems accounted for 15% of the variance in life satisfaction while psychological distress accounted for 29%. This suggests the importance of considering cognitive schemas and motivation beyond symptomatology when examining life satisfaction. C1 [Bello, Iruma] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02214 USA. [Bello, Iruma; Hayashi, Kentaro] Univ Hawaii Manoa, Dept Psychol, Honolulu, HI 96822 USA. [Steffen, John J.] Univ Hawaii Manoa, Social Sci Res Inst, Honolulu, HI 96822 USA. RP Bello, I (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 15 Parkman St,ACC 812, Boston, MA 02214 USA. EM irumabello@gmail.com; sjohn@hawaii.edu; hayashik@hawaii.edu FU State of Hawai'i's Adult Mental Health Division; Mental Health Services Research, Evaluation and Training Center FX We would like to thank the State of Hawai'i's Adult Mental Health Division and the Mental Health Services Research, Evaluation and Training Center for funding the project. NR 26 TC 4 Z9 4 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 SEP PY 2011 VL 20 IS 7 BP 1061 EP 1069 DI 10.1007/s11136-010-9842-y PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 812AW UT WOS:000294261100010 PM 21264519 ER PT J AU Kopans, DB Smith, RA Duffy, SW AF Kopans, Daniel B. Smith, Robert A. Duffy, Stephen W. TI Mammographic Screening and "Overdiagnosis" SO RADIOLOGY LA English DT Article ID CARCINOMA IN-SITU; BREAST-CANCER INCIDENCE; SPONTANEOUS REGRESSION; INTRADUCTAL-CARCINOMA; FOLLOW-UP; MORTALITY; PROGRAM; IMPACT; WOMEN; TRIAL C1 [Kopans, Daniel B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Smith, Robert A.] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30329 USA. [Duffy, Stephen W.] Queen Mary Univ London, Ctr Canc Prevent, Wolfson Inst Prevent Med, Barts & London Sch Med, London, England. RP Kopans, DB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St,Ambulatory Care Bldg,Suite 219, Boston, MA 02114 USA. EM dkopans@partners.org NR 43 TC 46 Z9 49 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2011 VL 260 IS 3 BP 616 EP 620 DI 10.1148/radiol.11110716 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808AI UT WOS:000293944700002 PM 21846757 ER PT J AU Bamberg, F Becker, A Schwarz, F Marcus, RP Greif, M von Ziegler, F Blankstein, R Hoffmann, U Sommer, WH Hoffmann, VS Johnson, TRC Becker, HCR Wintersperger, BJ Reiser, MF Nikolaou, K AF Bamberg, Fabian Becker, Alexander Schwarz, Florian Marcus, Roy P. Greif, Martin von Ziegler, Franz Blankstein, Ron Hoffmann, Udo Sommer, Wieland H. Hoffmann, Verena S. Johnson, Thorsten R. C. Becker, Hans-Christoph R. Wintersperger, Bernd J. Reiser, Maximilian F. Nikolaou, Konstantin TI Detection of Hemodynamically Significant Coronary Artery Stenosis: Incremental Diagnostic Value of Dynamic CT-based Myocardial Perfusion Imaging SO RADIOLOGY LA English DT Article ID CARDIAC COMPUTED-TOMOGRAPHY; AMERICAN-HEART-ASSOCIATION; FRACTIONAL FLOW RESERVE; ADENOSINE-STRESS; CLINICAL CARDIOLOGY; MAGNETIC-RESONANCE; ANGIOGRAPHY; DISEASE; INTERVENTION; RADIOLOGY AB Purpose: To determine the feasibility of computed tomography (CT)-based dynamic myocardial perfusion imaging for the detection of hemodynamically signifi cant coronary artery stenosis, as defined with fractional flow reserve (FFR). Materials and Methods: Institutional review board approval and informed patient consent were obtained before patient enrollment in the study. The study was HIPAA compliant. Subjects who were suspected of having or were known to have coronary artery disease underwent electrocardiographically triggered dynamic stress myocardial perfusion imaging. FFR measurement was performed within all main coronary arteries with a luminal narrowing of 50%-85%. Estimated myocardial blood flow (MBF) was derived from CT images by using a model-based parametric deconvolution method for 16 myocardial segments and was related to hemodynamically signifi cant coronary artery stenosis with an FFR of 0.75 or less in a blinded fashion. Conventional measures of diagnostic accuracy were derived, and discriminatory power analysis was performed by using logistic regression analysis. Results: Of 36 enrolled subjects, 33 (mean age, 68.1 years 6 10 [standard deviation]; 25 [76%] men, eight [24%] women) completed the study protocol. An MBF cut point of 75 mL/100 mL/min provided the highest discriminatory power (C statistic, 0.707; P <.001). While the diagnostic accuracy of CT for the detection of anatomically signifi cant coronary artery stenosis (. 50%) was high, it was low for the detection of hemodynamically signifi cant stenosis (positive predictive value [PPV] per coronary segment, 49%; 95% confidence interval [CI]: 36%, 60%). With use of estimated MBF to reclassify lesions depicted with CT angiography, 30 of 70 (43%) coronary lesions were graded as not hemodynamically signifi cant, which significantly increased PPV to 78% (95% CI: 61%, 89%; P =.02). The presence of a coronary artery stenosis with a corresponding MBF less than 75 mL/100 mL/min had a high risk for hemodynamic signifi cance (odds ratio, 86.9; 95% CI: 17.6, 430.4). Conclusion: Dynamic CT-based stress myocardial perfusion imaging may allow detection of hemodynamically signifi cant coronary artery stenosis. (C) RSNA, 2011 C1 [Bamberg, Fabian; Schwarz, Florian; Marcus, Roy P.; Sommer, Wieland H.; Johnson, Thorsten R. C.; Becker, Hans-Christoph R.; Wintersperger, Bernd J.; Reiser, Maximilian F.; Nikolaou, Konstantin] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-81377 Munich, Germany. [Becker, Alexander; Greif, Martin; von Ziegler, Franz] Univ Munich, Klinikum Grosshadern, Dept Cardiol, D-81377 Munich, Germany. [Bamberg, Fabian; Hoffmann, Udo] Harvard Univ, Sch Med, Dept Radiol, Cardiac MR PET CT Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Blankstein, Ron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hoffmann, Verena S.] Univ Munich, Inst Biomed Epidemiol, D-81377 Munich, Germany. RP Bamberg, F (reprint author), Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, Marchioninistr 15, D-81377 Munich, Germany. EM fbamberg@post.harvard.edu OI Nikolaou, Konstantin/0000-0003-2668-7325 FU Bayer Schering Pharma; Siemens Healthcare FX F. B. Financial activities related to the present article: institution received unrestricted grant from Bayer Schering Pharma. Financial activities not related to the present article: received payment for lectures including service on speakers bureaus from Siemens Medical Solutions. Other relationships: none to disclose. A. B. No potential conflicts of interest to disclose. F. S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received payment for speakers fee from Siemens Healthcare. Other relationships: none to disclose. R. P. M. No potential conflicts of interest to disclose. M. G. No potential conflicts of interest to disclose. F.v.Z. No potential conflicts of interest to disclose. R. B. No potential conflicts of interest to disclose. U. H. No potential conflicts of interest to disclose. W. H. S. No potential conflicts of interest to disclose. V. S. H. No potential conflicts of interest to disclose. T.R.C.J. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received honoraria for workshops and lectures from Siemens. Other relationships: none to disclose. H. C. R. B. No potential conflicts of interest to disclose. B.J.W. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received payment for lectures including service on speakers bureaus from Siemens Healthcare and Bayer. Other relationships: none to disclose. M. F. R. No potential conflicts of interest to disclose. K.N. Financial activities related to the present article: institution received unrestricted grant from Bayer Schering Pharma. Financial activities not related to the present article: received payment for lectures including service on speakers bureaus from Bayer Schering Pharma and Siemens Healthcare. Other relationships: none to disclose. NR 28 TC 112 Z9 116 U1 2 U2 7 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 2011 VL 260 IS 3 BP 689 EP 698 DI 10.1148/radiol.11110638 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808AI UT WOS:000293944700010 PM 21846761 ER PT J AU Shusterman, S Grant, FD Lorenzen, W Davis, RT Laffin, S Drubach, LA Fahey, FH Treves, ST AF Shusterman, Suzanne Grant, Frederick D. Lorenzen, William Davis, Royal T. Laffin, Stephen Drubach, Laura A. Fahey, Frederic H. Treves, S. Ted TI Iodine-131-labeled Meta-Iodobenzylguanidine Therapy of Children with Neuroblastoma: Program Planning and Initial Experience SO SEMINARS IN NUCLEAR MEDICINE LA English DT Review ID I DOSE-ESCALATION; REFRACTORY NEUROBLASTOMA; PHASE-I; I-131 METAIODOBENZYLGUANIDINE; MYELOABLATIVE CHEMOTHERAPY; META-IODOBENZYLGUANIDINE; IODINE-131-METAIODOBENZYLGUANIDINE; I-131-METAIODOBENZYLGUANIDINE; COMBINATION; 131-I-METAIODOBENZYLGUANIDINE AB Patients with high-risk neuroblastoma have a poor prognosis, especially in cases of recurrent or relapsed disease. lodine-131-labeled meta-iodobenzylguanidine ((131)I-MIBG) can be an effective and relatively well-tolerated agent for the treatment of refractory neuroblastoma. Establishing an MIBG therapy program requires a great deal of planning, availability of hospital resources, and the commitment of individuals with training and expertise in multiple disciplines. Providing (131)I-MIBG therapy requires physical facilities and procedures that permit patient care in compliance with the standards for occupational and community exposure to radiation. Establishment of a successful (131)I-MIBG therapy program also requires a detailed operational plan and appropriate education for caregivers, parents, and patients. Semin Nucl Med 41:354-363 (C) 2011 Elsevier Inc. All rights reserved. C1 [Grant, Frederick D.; Lorenzen, William; Davis, Royal T.; Laffin, Stephen; Drubach, Laura A.; Fahey, Frederic H.; Treves, S. Ted] Childrens Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02115 USA. [Shusterman, Suzanne] Dana Farber Canc Ctr, Dept Pediat Oncol, Boston, MA USA. [Shusterman, Suzanne] Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. [Grant, Frederick D.; Drubach, Laura A.; Fahey, Frederic H.; Treves, S. Ted] Harvard Univ, Sch Med, Joint Program Nucl Med, Boston, MA USA. RP Treves, ST (reprint author), Childrens Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM treves@childrens.harvard.edu NR 28 TC 10 Z9 10 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0001-2998 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD SEP PY 2011 VL 41 IS 5 BP 354 EP 363 DI 10.1053/j.semnuclmed.2011.06.001 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 810CR UT WOS:000294103500005 PM 21803185 ER PT J AU Powner, MW Sutherland, JD Szostak, JW AF Powner, Matthew W. Sutherland, John D. Szostak, Jack W. TI The Origins of Nucleotides SO SYNLETT LA English DT Article DE nucleotides; chemoselectivity; multicomponent reactions; rearrangement; photochemistry ID CATALYZED PHOSPHORYLATION REACTIONS; ADENOSINE CYCLIC 2',3'-PHOSPHATE; PREBIOTIC SYNTHESIS; AMINO-ACIDS; ALPHA-AMINONITRILES; PURINE PRECURSORS; STRECKER SYSTEMS; HYDROGEN CYANIDE; AMMONIUM CYANIDE; RIBOSE AB The origins of life represent one of the most fundamental chemical questions being addressed by modern science. One of the longstanding mysteries of this field is what series of chemical reactions could lead to the molecular biologists dream; a pool of homochiral nucleotides? Here we summarize those results we consider to be historically important and outline our recently published research aimed at understanding the chemoselective origins of the canonical ribonucleotides. C1 [Powner, Matthew W.; Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Powner, Matthew W.; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Powner, Matthew W.; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sutherland, John D.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England. RP Powner, MW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM powner@molbio.mgh.harvard.edu OI Powner, Matthew/0000-0002-6368-3190 FU EPSRC; Howard Hughes Medical Institute FX We should like to thank Dr Caroline Powner for helpful comments, advice, and support. This work was supported by the EPSRC, a Harvard Origins Fellowship and the Howard Hughes Medical Institute to M. W. P. J.W.S is an investigator for the Howard Hughes Medical Institute. NR 82 TC 23 Z9 24 U1 9 U2 93 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0936-5214 EI 1437-2096 J9 SYNLETT JI Synlett PD SEP PY 2011 IS 14 BP 1956 EP 1964 DI 10.1055/s-0030-1261177 PG 9 WC Chemistry, Organic SC Chemistry GA 810WZ UT WOS:000294161400002 ER PT J AU Ueno, T Yamada, A Ito, T Yeung, MY Gorbatov, R Shimizu, T Abdi, R Sayegh, MH Auchincloss, H Najafian, N AF Ueno, Takuya Yamada, Akira Ito, Toshiro Yeung, Melissa Y. Gorbatov, Rostic Shimizu, Tetsunosuke Abdi, Reza Sayegh, Mohamed H. Auchincloss, Hugh, Jr. Najafian, Nader TI Role of Nuclear Factor of Activated T Cell (NFAT) Transcription Factors in Skin and Vascularized Cardiac Allograft Rejection SO TRANSPLANTATION LA English DT Letter ID RESPONSES; MICE; DIFFERENTIATION; CYTOKINES C1 [Ueno, Takuya; Yeung, Melissa Y.; Shimizu, Tetsunosuke; Abdi, Reza; Sayegh, Mohamed H.; Najafian, Nader] Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr, Boston, MA 02115 USA. [Ueno, Takuya; Yamada, Akira; Ito, Toshiro; Auchincloss, Hugh, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Unit,Surg Serv, Boston, MA 02115 USA. [Ueno, Takuya; Yeung, Melissa Y.; Shimizu, Tetsunosuke; Abdi, Reza; Sayegh, Mohamed H.; Najafian, Nader] Harvard Univ, Childrens Hosp, Sch Med, Transplantat Res Ctr, Boston, MA 02115 USA. [Gorbatov, Rostic] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02115 USA. RP Ueno, T (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplantat Res Ctr, Boston, MA 02115 USA. EM ueno.takuya@mgh.harvard.edu; nnajafian@rics.bwh.harvard.edu FU NIAID NIH HHS [1KO8AI064335-01A2, AI31541-05] NR 14 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP PY 2011 VL 92 IS 5 BP E26 EP E27 DI 10.1097/TP.0b013e318228061c PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 811VV UT WOS:000294245400001 PM 21866037 ER PT J AU Butt, AA McGinnis, K Skanderson, M Justice, AC AF Butt, Adeel A. McGinnis, Kathleen Skanderson, Melissa Justice, Amy C. TI A Comparison of Treatment Eligibility for Hepatitis C Virus in HCV-Monoinfected Versus HCV/HIV-Coinfected Persons in Electronically Retrieved Cohort of HCV-Infected Veterans SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HEPATOCELLULAR-CARCINOMA; PEGINTERFERON ALPHA-2A; HIV; RISK; PREVALENCE; PREDICTORS; MANAGEMENT; RIBAVIRIN; CIRRHOSIS; THERAPY AB Treatment rates for hepatitis C virus (HCV) are low in actual clinical settings. However, the proportion of patients eligible for treatment, especially among those coinfected with HIV, is not well known. Our aim was to determine and compare the rates for HCV treatment eligibility among HCV and HCV-HIV-coinfected persons. We assembled a national cohort of HCV-infected veterans in care from 1998-2003, using the VA National Patient Care Database for demographic/clinical information, the Pharmacy Benefits Management database for pharmacy records, and the Decision Support Systems database for laboratory data. We compared the HCV-monoinfected and HCV-HIV-coinfected subjects for treatment indications and eligibility using current treatment guidelines. Of the 27,452 subjects with HCV and 1225 with HCV-HIV coinfection, 74.0% and 84.6% had indications for therapy and among these, 43.9% of HCV-monoinfected and 28.4% of HCV-HIV-coinfected subjects were eligible for treatment. Anemia, decompensated liver disease (DLD), chronic obstructive pulmonary disease (COPD), recent alcohol abuse, and coronary artery disease were the most common contraindications in the HCV, and anemia, DLD, renal failure, recent drug abuse, and COPD in the HCV-HIV-coinfected group. Among those eligible for treatment, only 23% of the HCV-monoinfected and 15% of the HCV-HIV-coinfected subjects received any treatment for HCV. Most veterans with HCV are not eligible for treatment according to the current guidelines. Even for those who are eligible for treatment, only a minority is prescribed treatment. Several contraindications are modifiable and aggressive management of those may improve treatment prescription rates. C1 [Butt, Adeel A.] Univ Pittsburgh, Med Ctr, Sch Med, Pittsburgh, PA 15213 USA. [Butt, Adeel A.; McGinnis, Kathleen; Skanderson, Melissa] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. RP Butt, AA (reprint author), Univ Pittsburgh, Med Ctr, Sch Med, 3601 5th Ave,Suite 3A,Falk Med Bldg, Pittsburgh, PA 15213 USA. EM aabutt@pitt.edu FU NIAAA NIH HHS [U24 AA020794] NR 30 TC 9 Z9 9 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 2011 VL 27 IS 9 BP 973 EP 979 DI 10.1089/aid.2011.0004 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 810XQ UT WOS:000294163700007 PM 21338329 ER PT J AU Serrano-Pozo, A Frosch, MP Masliah, E Hyman, BT AF Serrano-Pozo, Alberto Frosch, Matthew P. Masliah, Eliezer Hyman, Bradley T. TI Neuropathological Alterations in Alzheimer Disease SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article AB The neuropathological hallmarks of Alzheimer disease (AD) include "positive" lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and "negative" lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between "normal" aging and AD dementia, and that the amyloid plaque build-up occurs primarily before the onset of cognitive deficits, while neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. Importantly, these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloid PET and volumetric MRI. C1 [Serrano-Pozo, Alberto; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, Alzheimer Res Unit, MassGeneral Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. [Serrano-Pozo, Alberto; Frosch, Matthew P.; Hyman, Bradley T.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Neurosci, San Diego Sch Med, La Jolla, CA 92093 USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Pathol, San Diego Sch Med, La Jolla, CA 92093 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, MassGeneral Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA. EM bhyman@partners.org RI SERRANO-POZO, ALBERTO/F-5119-2013; OI SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU National Institutes of Health [AG5131, AG18840, AG22074, NS057096, AG10435, P50AG05134, AG08487]; Fundacion Alfonso Martin Escudero (Madrid, Spain) FX This work was funded by the National Institutes of Health grants AG5131, AG18840, AG22074, NS057096, and AG10435 (to E.M.), and P50AG05134 and AG08487 (to B.T.H. and M.P.F.). A.S.P. was supported with a Research Fellowship from Fundacion Alfonso Martin Escudero (Madrid, Spain). NR 230 TC 344 Z9 356 U1 13 U2 40 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD SEP PY 2011 VL 1 IS 1 AR a006189 DI 10.1101/cshperspect.a006189 PG 23 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V27OZ UT WOS:000208623800001 PM 22229116 ER PT J AU Cote, GM Canellos, GP AF Cote, Gregory M. Canellos, George P. TI Can Low-Risk, Early-Stage Patients with Hodgkin Lymphoma Be Spared Radiotherapy? SO CURRENT HEMATOLOGIC MALIGNANCY REPORTS LA English DT Article DE Hodgkin lymphoma; Hodgkin's disease; Radiation therapy; Radiotherapy; Combined modality; therapy; Low-risk patients; Early-stage disease; Stage I; Stage II; Treatment; Chemotherapy; Complications; Toxicity; EFRT; IFRT; Breast cancer; Cardiovascular disease ID INVOLVED-FIELD RADIOTHERAPY; CORONARY-ARTERY-DISEASE; LONG-TERM SURVIVAL; BREAST-CANCER RISK; RADIATION-THERAPY; ABVD CHEMOTHERAPY; 5-YEAR SURVIVORS; YOUNG-WOMEN; FOLLOW-UP; 2 CYCLES AB Advances in the treatment of Hodgkin lymphoma since about 1970 have led to a remarkable improvement in the long-term outcomes of what was once considered an incurable disease. The prolonged survival of cured patients has revealed new issues concerning the toxicity of successful therapy, however, including an increased risk of secondary malignancies and end-organ damage such as heart disease. This concern has led to the clinical research question of whether the de-escalation of treatment intensity could allow high cure rates to continue with less long-term toxicity. In young patients with favorable early-stage disease, the challenge has been to use systemic therapy while omitting radiation therapy as part of the initial treatment. This review briefly summarizes past data and updates readers regarding recent publications on this topic. C1 [Canellos, George P.] Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. [Cote, Gregory M.] Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. RP Canellos, GP (reprint author), Dana Farber Harvard Canc Ctr, Dana 1B14B,44 Binney St, Boston, MA 02115 USA. EM George_Canellos@dfci.harvard.edu OI Cote, Gregory/0000-0003-0181-886X NR 41 TC 2 Z9 2 U1 0 U2 1 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1558-8211 J9 CURR HEMATOL MALIG R JI Curr. Hematol. Malig. Rep. PD SEP PY 2011 VL 6 IS 3 BP 180 EP 186 DI 10.1007/s11899-011-0088-8 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 023BP UT WOS:000310008200005 PM 21503634 ER PT J AU Cyganek, K Hebda-Szydlo, A Skupien, J Katra, B Janas, I Kaim, I Borys, S Szopa, M Reron, A Malecki, MT AF Cyganek, K. Hebda-Szydlo, A. Skupien, J. Katra, B. Janas, I. Kaim, I. Borys, S. Szopa, M. Reron, A. Malecki, M. T. TI Glycaemic control in post-pregnancy follow-up in type 1 diabetes women SO DIABETOLOGIA LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 12-16, 2011 CL Lisbon, PORTUGAL SP European Assoc Study Diabet (EASD) C1 [Cyganek, K.; Hebda-Szydlo, A.; Katra, B.; Szopa, M.; Malecki, M. T.] Jagiellonian Univ, Dept Metab Dis, Coll Med, Krakow, Poland. [Skupien, J.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Janas, I.; Borys, S.] Univ Hosp, Dept Metab Dis, Krakow, Poland. [Kaim, I.; Reron, A.] Jagiellonian Univ, Dept Obstet & Perinatol, Coll Med, Krakow, Poland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2011 VL 54 SU 1 MA 1203 BP S484 EP S485 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990ZT UT WOS:000307671302397 ER PT J AU Gastaldelli, A Natali, A Gall, WE Lerin, C Patti, ME Petrie, J Balkau, B Anderwald, CH Laville, M Gabriel, R Ferrannini, E AF Gastaldelli, A. Natali, A. Gall, W. E. Lerin, C. Patti, M. E. Petrie, J. Balkau, B. Anderwald, C. H. Laville, M. Gabriel, R. Ferrannini, E. CA RISC Investigators TI Plasma alpha-hydroxybutyrate and linoleoyl-glycerolphosphocholine as new markers of insulin resistance and fatty liver disease SO DIABETOLOGIA LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 12-16, 2011 CL Lisbon, PORTUGAL SP European Assoc Study Diabet (EASD) C1 [Gastaldelli, A.] CNR, Inst Clin Physiol, Metab Unit, I-56100 Pisa, Italy. [Natali, A.; Ferrannini, E.] Univ Pisa, I-56100 Pisa, Italy. [Gall, W. E.] Metabolon Inc, Res Triangle Pk, NC USA. [Lerin, C.] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain. [Patti, M. E.] Harvard Univ, Sch Med, Boston, MA USA. [Patti, M. E.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Balkau, B.] INSERM, CESP, Villejuif, France. [Petrie, J.] Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland. [Balkau, B.] Univ Paris 11, Paris, France. [Anderwald, C. H.] Univ Vienna, A-1010 Vienna, Austria. [Laville, M.] Univ Lyon, Lyon, France. [Gabriel, R.] Univ Autonoma Madrid, E-28049 Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2011 VL 54 SU 1 MA 595 BP S245 EP S245 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990ZT UT WOS:000307671301250 ER PT J AU Menzaghi, C Bacci, S Salvemini, L Powers, C Fini, G Rizza, S Goheen, E De Bonis, C Kanagaki, A Mangiacotti, D Federici, M Doria, A Trischitta, V AF Menzaghi, C. Bacci, S. Salvemini, L. Powers, C. Fini, G. Rizza, S. Goheen, E. De Bonis, C. Kanagaki, A. Mangiacotti, D. Federici, M. Doria, A. Trischitta, V. TI Serum resistin is associated with coronary artery disease and predicts major cardiovascular events in type 2 diabetes patients SO DIABETOLOGIA LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 12-16, 2011 CL Lisbon, PORTUGAL SP European Assoc Study Diabet (EASD) C1 [Menzaghi, C.; Salvemini, L.; Fini, G.; De Bonis, C.; Mangiacotti, D.; Trischitta, V.] IRCCS, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Bacci, S.] IRCCS, Unit Endocrinol, San Giovanni Rotondo, Italy. [Powers, C.; Goheen, E.; Kanagaki, A.; Doria, A.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Rizza, S.; Federici, M.] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy. [Doria, A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RI Trischitta, Vincenzo/K-1487-2016 OI Trischitta, Vincenzo/0000-0003-1174-127X NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2011 VL 54 SU 1 MA 124 BP S58 EP S58 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990ZT UT WOS:000307671300125 ER PT J AU Scott, RA Manning, AK Hivert, MF Bouatia-Naji, N Grimsby, J Liu, CT Chen, H Bielak, LF Rasmussen-Torvik, L Wareham, NJ Watanabe, RM Florez, JC Langenberg, C Dupuis, J Meigs, JB AF Scott, R. A. Manning, A. K. Hivert, M. -F. Bouatia-Naji, N. Grimsby, J. Liu, C. -T. Chen, H. Bielak, L. F. Rasmussen-Torvik, L. Wareham, N. J. Watanabe, R. M. Florez, J. C. Langenberg, C. Dupuis, J. Meigs, J. B. TI Genome-wide joint meta-analysis of SNP by BMI interaction on fasting insulin: a MAGIC study SO DIABETOLOGIA LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 12-16, 2011 CL Lisbon, PORTUGAL SP European Assoc Study Diabet (EASD) C1 [Scott, R. A.; Wareham, N. J.; Langenberg, C.] MRC Epidemiol Unit, Cambridge, England. [Manning, A. K.; Liu, C. -T.; Chen, H.; Dupuis, J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Hivert, M. -F.] Univ Sherbrooke, Quebec City, PQ, Canada. [Bouatia-Naji, N.] Inst Pasteur, F-59019 Lille, France. [Grimsby, J.; Florez, J. C.; Meigs, J. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bielak, L. F.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Rasmussen-Torvik, L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Watanabe, R. M.] USC, Keck Sch Med, Los Angeles, CA USA. [Florez, J. C.; Meigs, J. B.] Harvard Univ, Sch Med, Boston, MA USA. [Dupuis, J.] NHLBI, Framingham Heart Study, Framingham, MA USA. RI BOUATIA-NAJI, NABILA/D-5863-2013 NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2011 VL 54 SU 1 MA 166 BP S76 EP S76 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990ZT UT WOS:000307671300167 ER PT J AU Tanti, JF Ceppo, F Gremeaux, T Jager, J Bezy, O Le Marchand-Brustel, Y Cormont, M AF Tanti, J. -F. Ceppo, F. Gremeaux, T. Jager, J. Bezy, O. Le Marchand-Brustel, Y. Cormont, M. TI Implication of the inflammatory kinase Tpl2 in the deleterious effects of cytokines and macrophages on adipocytes functions SO DIABETOLOGIA LA English DT Meeting Abstract CT 47th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD) CY SEP 12-16, 2011 CL Lisbon, PORTUGAL SP European Assoc Study Diabet (EASD) C1 [Tanti, J. -F.; Ceppo, F.; Gremeaux, T.; Jager, J.; Le Marchand-Brustel, Y.; Cormont, M.] Fac Med Nice, INSERM, U895, Team Cellular & Mol Pathophysiol Obes, F-06034 Nice, France. [Tanti, J. -F.; Ceppo, F.; Gremeaux, T.; Jager, J.; Le Marchand-Brustel, Y.; Cormont, M.] Univ Nice Sophia Antipolis, Nice, France. [Bezy, O.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2011 VL 54 SU 1 MA 735 BP S297 EP S297 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 990ZT UT WOS:000307671301390 ER PT J AU Goldhirsch, A Gelber, R AF Goldhirsch, A. Gelber, R. CA IBCSG TI Adjuvant Systemic Treatment for Women with Breast Cancer: The Future of Clinical Trials SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 [Goldhirsch, A.] European Inst Oncol, Milan, Italy. [Gelber, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2011 VL 47 SU 2 MA G2 BP 1 EP 2 PG 2 WC Oncology SC Oncology GA V40HU UT WOS:000209470500003 ER PT J AU Baselga, J Campone, M Sahmoud, T Piccart, M Burris, H Rugo, H Noguchi, S Gnant, M Mukhopadhyay, P Hortobagyi, G AF Baselga, J. Campone, M. Sahmoud, T. Piccart, M. Burris, H. Rugo, H. Noguchi, S. Gnant, M. Mukhopadhyay, P. Hortobagyi, G. TI Everolimus in Combination with Exemestane for Postmenopausal Women with Advanced Breast Cancer Who Are Refractory to Letrozole or Anastrozole: Results of the BOLERO-2 Phase III Trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 [Baselga, J.] Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. [Campone, M.] Ctr Reg Rene Gauducheau, Dept Med Oncol, Nantes St Herblain, France;. [Sahmoud, T.] Novartis Pharmaceut, Global Oncol Dev, Florham Pk, NJ USA. [Piccart, M.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. [Burris, H.] Sarah Cannon Res Inst, Drug Dev Program, Nashville, TN USA. [Rugo, H.] Univ Calif San Francisco, Dept Med Hematol Oncol, San Francisco, CA 94143 USA. [Noguchi, S.] Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan. [Gnant, M.] Med Univ Vienna, Dept Surg, Ctr Comprehens Canc, Vienna, Austria. [Mukhopadhyay, P.] Novartis Pharmaceut, Oncol BDM, Florham Pk, NJ USA. [Hortobagyi, G.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2011 VL 47 SU 2 MA 9LBA BP 6 EP 7 PG 3 WC Oncology SC Oncology GA V40HU UT WOS:000209470500016 ER PT J AU McArthur, G Hauschild, A Robert, C Haanen, JB Ascierto, P Lee, RJ Nolop, K Nelson, B Flaherty, KT Chapman, PB AF McArthur, G. Hauschild, A. Robert, C. Haanen, J. B. Ascierto, P. Lee, R. J. Nolop, K. Nelson, B. Flaherty, K. T. Chapman, P. B. TI Vemurafenib Improves Overall Survival Compared to Dacarbazine in Advanced BRAFV600E-mutated Melanoma: Updated Survival Results From a Phase III Randomised, Open-label, Multicentre Trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 [McArthur, G.] Peter MacCallum Canc Ctr, Med Oncol, Melbourne, Vic, Australia. [Hauschild, A.] Univ Klinikum Schleswig Holstein, Dermatol, Kiel, Germany. [Robert, C.] Canc Inst Gustave Roussy, Villejuif, France. [Haanen, J. B.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands. [Ascierto, P.] Inst Nazl Tumori Pascale, Med Oncol & Innovat Therapy, Naples, Italy. [Lee, R. J.] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Nolop, K.] Plexxikon Inc, Berkeley, CA USA. [Nelson, B.] Genentech Inc, San Francisco, CA 94080 USA. [Flaherty, K. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chapman, P. B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 EI 1879-0852 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2011 VL 47 SU 2 MA 28LBA BP 14 EP 14 PG 1 WC Oncology SC Oncology GA V40HU UT WOS:000209470500035 ER PT J AU Braun, AB Gibbons, FK Litonjua, AA Giovannucci, E Christopher, K AF Braun, A. B. Gibbons, F. K. Litonjua, A. A. Giovannucci, E. Christopher, Kb. TI LOW SERUM 25-HYDROXYVITAMIN D AT CRITICAL CARE INITIATION IS ASSOCIATED WITH INCREASED MORTALITY SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract C1 [Braun, A. B.; Christopher, Kb.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Gibbons, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Litonjua, A. A.] Brigham & Womens Hosp, Pulm & Crit Care Div, Boston, MA 02115 USA. [Litonjua, A. A.] Brigham & Womens Hosp, Charming Lab, Boston, MA 02115 USA. [Giovannucci, E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Giovannucci, E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2011 VL 37 SU 1 MA 0792 BP S203 EP S203 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA V34JN UT WOS:000209082801016 ER PT J AU David, S Ghosh, CC van Slyke, P Khankin, EV Kumpers, P Shushakova, N Karumanchi, SA Dumont, D Parikh, SM AF David, S. Ghosh, C. C. van Slyke, P. Khankin, E. V. Kuempers, P. Shushakova, N. Karumanchi, S. A. Dumont, D. Parikh, S. M. TI EFFECTS OF A SYNTHETIC PEG-YLATED TIE-2 AGONIST PEPTIDE ON ENDOTOXEMIC LUNG INJURY AND MORTALITY SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract C1 [David, S.; Ghosh, C. C.; Khankin, E. V.; Karumanchi, S. A.; Parikh, S. M.] Harvard Univ, Sch Med, BIDMC, CVBR, Boston, MA USA. [David, S.; Kuempers, P.; Shushakova, N.] Hannover Med Sch, Hannover, Germany. [van Slyke, P.; Dumont, D.] Univ Toronto, Smmybrook Res Inst, Toronto, ON, Canada. [van Slyke, P.; Dumont, D.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2011 VL 37 SU 1 MA 0445 BP S117 EP S117 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA V34JN UT WOS:000209082800446 ER PT J AU Lipnick, MS Braun, AB Bazick, HS Chang, D Cheung, J Gibbons, FK Christopher, KB AF Lipnick, M. S. Braun, A. B. Bazick, H. S. Chang, D. Cheung, J. Gibbons, F. K. Christopher, K. B. TI DIFFERENCE BETWEEN CRITICAL CARE INITIATION ANION GAP AND PRE-HOSPITAL ANION GAP IS PREDICTIVE OF MORTALITY IN CRITICAL ILLNESS SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract C1 [Lipnick, M. S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Braun, A. B.; Chang, D.; Christopher, K. B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Bazick, H. S.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Cheung, J.] Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada. [Gibbons, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2011 VL 37 SU 1 MA 0657 BP S170 EP S170 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA V34JN UT WOS:000209082800658 ER PT J AU McMahon, GM Gibbons, FK Christopher, KB AF McMahon, G. M. Gibbons, F. K. Christopher, K. B. TI ASSOCIATION OF HYPERKALEMIA AT CRITICAL CARE INITIATION AND MORTALITY SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract C1 [McMahon, G. M.; Christopher, K. B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. [Gibbons, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2011 VL 37 SU 1 MA 0656 BP S169 EP S169 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA V34JN UT WOS:000209082800657 ER PT J AU Mendu, ML Zager, S Gibbons, FK Christopher, KB AF Mendu, M. L. Zager, S. Gibbons, F. K. Christopher, K. B. TI RELATIONSHIP BETWEEN NEIGHBORHOOD POVERTY RATE AND BLOOD-STREAM INFECTIONS IN THE CRITICALLY ILL SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract C1 [Mendu, M. L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Zager, S.] Harvard Univ, Sch Med, Boston, MA USA. [Gibbons, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christopher, K. B.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2011 VL 37 SU 1 MA 0047 BP S17 EP S17 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA V34JN UT WOS:000209082800048 ER PT J AU Bleier, BS Debnath, I Harvey, RJ Schlosser, RJ AF Bleier, Benjamin S. Debnath, Indranil Harvey, Richard J. Schlosser, Rodney J. TI Temporospatial quantification of fluorescein-labeled sinonasal irrigation delivery SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article DE intranasal drug delivery; sinus irrigation; topical therapeutics; fluorescein distribution; blue light filter ID SINUS SURGERY; SPRAY AB Background: Treatment of sinonasal disease is predicated on the delivery and retention of the agent at the desired location. Despite multiple distribution studies, there remains a need for a method capable quantifying not only the site and amount of agent deposition but the rate of clearance as well. Methods: Five patients underwent endoscopic image capture of 3 subsites over 15 minutes following fluorescein-dyed irrigation using a squeeze bottle, nasal saline spray, or nasal gel spray. Area and intensity staining were quantified using a graphics editing program. Total intensity scores were compared using a Student t test. Results: The squeeze bottle was the only method demonstrating delivery to the oropharynx (37 +/- 22 mm(2)). The nasal gel resulted in the greatest coverage of the middle turbinate region (10 +/- 15 mm(2)) while the nasal saline spray (75 +/- 31 mm(2)) resulted in the greatest inferior turbinate coverage. No significant differences in clearance rates were found between delivery methods at any subsite. Conclusion: This method is capable of quantifying both the area and intensity of fluorescein deposition using a variety of delivery methods. While small variations in subsite coverage were noted, all methods resulted in significant internal valve deposition. Despite differences in delivery volume and viscosity, all methods resulted in similar rates of fluorescein clearance. (C) 2011 ARS-AAOA, LLC. C1 [Bleier, Benjamin S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Debnath, Indranil] Washington Univ, Sch Med, St Louis, MO USA. [Harvey, Richard J.] St Vincents Hosp, Sydney, NSW 2010, Australia. [Schlosser, Rodney J.] Med Univ S Carolina, Charleston, SC 29425 USA. RP Bleier, BS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM bleierb@gmail.com NR 7 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD SEP-OCT PY 2011 VL 1 IS 5 BP 361 EP 365 DI 10.1002/alr.20041 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 007YC UT WOS:000308923300008 PM 22287467 ER PT J AU Cashman, E Woo, SB AF Cashman, E. Woo, S. B. TI DNA Aneuploidy in Oral Leukoplakia: A Case Series and Review of the Literature SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Cashman, E.; Woo, S. B.] Dana Farber Canc Inst, Dept CMOP, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD SEP PY 2011 VL 180 SU 8 MA 91 BP S281 EP S281 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA V27YP UT WOS:000208648800092 ER PT J AU Cashman, E Lehrman, M Woo, SB AF Cashman, E. Lehrman, M. Woo, S. B. TI P 16 and its Role in HPV-Positive Koliocytic Dyspalsia (KCD) of the Anterior Oral Cavity: A Case Series SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Cashman, E.; Lehrman, M.; Woo, S. B.] Dana Farber Canc Inst, Dept CMOP, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD SEP PY 2011 VL 180 SU 8 MA 86 BP S279 EP S279 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA V27YP UT WOS:000208648800087 ER PT J AU Hannon, N Tan, KM Noone, I O'Donnell, M Chroinin, DN Audebert, HJ Schenkel, J Tanne, D Molshatski, N Ay, H Arsava, M Crowe, M Kelly, PJ AF Hannon, Niamh Tan, Kit Mun Noone, Imelda O'Donnell, Martin Chroinin, Danielle Ni Audebert, Heinrich J. Schenkel, Johannes Tanne, David Molshatski, Noa Ay, Hakan Arsava, Murat Crowe, Morgan Kelly, Peter J. TI Association between therapeutic INR, survival and reduced disability in atrial fibrillation and stroke-systematic review and meta-analysis SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Meeting Abstract C1 [Hannon, Niamh; Chroinin, Danielle Ni; Kelly, Peter J.] Mater Univ Hosp UCD, Dublin, Ireland. [Tan, Kit Mun; Noone, Imelda; Crowe, Morgan] St Vincents Univ Hosp, Dublin 4, Ireland. [O'Donnell, Martin] McMaster Univ, Hamilton, ON, Canada. [Audebert, Heinrich J.] Charite, D-13353 Berlin, Germany. [Schenkel, Johannes] Stadt Klinikum Munchen GmbH, Klinikum Harlaching, Munich, Germany. [Tanne, David; Molshatski, Noa] Chaim Sheba Med Ctr, Tel Aviv, Israel. [Tanne, David; Molshatski, Noa] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Ay, Hakan; Arsava, Murat] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Tan, Kit Mun/D-5301-2013; Tanne, David/F-2560-2010 OI Tanne, David/0000-0002-6699-2220 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD SEP PY 2011 VL 180 SU 10 BP S328 EP S329 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA V27YR UT WOS:000208649000024 ER PT J AU Ryan, CM Antoon, A Fagan, SP Goverman, J Lawlor, D Sheridan, RL Tompkins, RG AF Ryan, Colleen M. Antoon, Alia Fagan, Shawn P. Goverman, Jeremy Lawlor, David Sheridan, Robert L. Tompkins, Ronald G. TI Considerations for Preparedness for a Pediatric Burn Disaster SO JOURNAL OF BURN CARE & RESEARCH LA English DT Letter ID CHILDREN C1 [Ryan, Colleen M.; Fagan, Shawn P.; Goverman, Jeremy; Lawlor, David; Sheridan, Robert L.; Tompkins, Ronald G.] Massachusetts Gen Hosp, Sumner Redstone Burn Ctr, Surg Serv, Boston, MA 01890 USA. [Ryan, Colleen M.; Antoon, Alia; Fagan, Shawn P.; Goverman, Jeremy; Lawlor, David; Sheridan, Robert L.; Tompkins, Ronald G.] Shriners Hosp Children, Boston, MA USA. [Antoon, Alia] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp Children, Boston, MA 02115 USA. [Lawlor, David] Harvard Univ, Sch Med, Dept Pediat Surg, Massachusetts Gen Hosp Children, Boston, MA 02115 USA. RP Ryan, CM (reprint author), Massachusetts Gen Hosp, Sumner Redstone Burn Ctr, Surg Serv, Bigelow 1302,55 Fruit St, Boston, MA 01890 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD SEP-OCT PY 2011 VL 32 IS 5 BP E165 EP E166 DI 10.1097/BCR.0b013e31822ac9a4 PG 2 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 817PW UT WOS:000294687300003 PM 21772149 ER PT J AU Min, JK Berman, DS Budoff, MJ Jaffer, FA Leipsic, J Leon, MB Mancini, GBJ Mauri, L Schwartz, RS Shaw, LJ AF Min, James K. Berman, Daniel S. Budoff, Matthew J. Jaffer, Farouc A. Leipsic, Jonathon Leon, Martin B. Mancini, G. B. John Mauri, Laura Schwartz, Robert S. Shaw, Leslee J. TI Rationale and design of the DeFACTO (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography) study SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Computed tomography; Fractional flow reserve; Coronary artery disease AB BACKGROUND: Coronary computed tomographic angiography (CTA) allows for noninvasive identification of anatomic coronary artery disease (CAD) severity but does not discriminate whether a stenosis causes ischemia. Computational fluid dynamic techniques applied to CTA images now permit noninvasive computation of fractional flow reserve (FFR), a measure of lesion-specific ischemia, but the diagnostic performance of computed FFR (FFRCT) as compared with measured FFR at the time of invasive coronary angiography remains unexplored. OBJECTIVE: We determined the diagnostic accuracy of noninvasive FFRCT for the detection and exclusion of ischemia-causing stenoses. METHODS: DeFACTO (NCT01233518) is a prospective, international, multicenter study of 238 patients designed to evaluate the diagnostic performance of FFRCT for the detection of hemodynamically significant coronary artery stenoses identified by CTA, compared with invasive FFR as a reference standard. FFR values <= 0.80 will be considered hemodynamically significant. Patients enrolled in the DeFACTO study will undergo CTA, invasive coronary angiography, and 3-vessel FFR in the left anterior descending artery, left circumflex artery, and right coronary artery distributions. FFRCT will be computed with acquired CTA images, without modification to CTA image acquisition protocols and without additional image acquisition. Blinded core laboratory interpretation will be performed for CTA, invasive coronary angiography, FFR, and FFRCT. RESULTS: The primary endpoint of the DeFACTO study is the per-patient diagnostic accuracy of FFRCT for noninvasive assessment of the hemodynamic significance of CAD, compared with FFR during invasive coronary angiography as a reference standard. The secondary endpoints include additional per-patient as well as per-vessel diagnostic performance characteristics, including sensitivity, specificity, positive predictive value, and negative predictive value. CONCLUSION: The DeFACTO study will determine whether the addition of FFRCT to conventional CTA improves the diagnosis of hemodynamically significant CAD. (C) 2011 Published by Elsevier Inc on behalf of Society of Cardiovascular Computed Tomography. C1 [Min, James K.] Cedars Sinai Med Ctr, Dept Med Imaging & Biomed Sci, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA. [Berman, Daniel S.] Cedars Sinai Med Ctr, Dept Imaging, Los Angeles, CA 90048 USA. [Budoff, Matthew J.] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Leipsic, Jonathon] St Pauls Hosp, Dept Radiol, Vancouver, BC V6Z 1Y6, Canada. [Leipsic, Jonathon; Mancini, G. B. John] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Leon, Martin B.] Columbia Univ, Med Ctr, Ctr Intervent Vasc Therapy, New York, NY USA. [Leon, Martin B.] New York Presbyterian Hosp, New York, NY USA. [Mancini, G. B. John] Vancouver Gen Hosp, Dept Med, Div Cardiol, Vancouver, BC, Canada. [Mauri, Laura] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Schwartz, Robert S.] Minneapolis Heart Inst & Fdn, Minneapolis, MN USA. [Shaw, Leslee J.] Emory Univ, Sch Med, Div Cardiol, Dept Med, Atlanta, GA 30322 USA. RP Min, JK (reprint author), Cedars Sinai Med Ctr, Dept Med Imaging & Biomed Sci, Cedars Sinai Heart Inst, 8700 Beverly Blvd,S Taper Bldg 1258, Los Angeles, CA 90048 USA. EM james.min@cshs.org OI Jaffer, Farouc/0000-0001-7980-384X FU HeartFlow, Inc; HeartFlow FX HeartFlow, Inc, is the sponsor of this study. The authors report no conflicts of interest or received any funding or payment from HeartFlow. NR 23 TC 53 Z9 55 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD SEP-OCT PY 2011 VL 5 IS 5 BP 301 EP 309 DI 10.1016/j.jcct.2011.08.003 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA V34CI UT WOS:000209064100005 PM 21930103 ER PT J AU Pugh, MJV Starner, CI Amuan, ME Berlowitz, DR Horton, M Marcum, ZA Hanlon, JT AF Pugh, Mary Jo V. Starner, Catherine I. Amuan, Megan E. Berlowitz, Dan R. Horton, Monica Marcum, Zachary A. Hanlon, Joseph T. TI Exposure to Potentially Harmful Drug-Disease Interactions in Older Community-Dwelling Veterans Based on the Healthcare Effectiveness Data and Information Set Quality Measure: Who Is at Risk? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE drug disease interaction; HEDIS measures; potentially inappropriate prescribing; aged; pharma-coepidemiology ID INAPPROPRIATE MEDICATION USE; ELDERLY VETERANS; EMERGENCY-DEPARTMENT; CONSENSUS PANEL; ADULTS; PHARMACOTHERAPY; POPULATION; EPILEPSY; CRITERIA; FRAIL AB OBJECTIVES: To identify prevalence and risk factors for exposure to drug-disease interactions included in the Healthcare Effectiveness Data and Information Set (HEDIS) Drug-Disease Interaction (Rx-DIS) measure. DESIGN: Cross-sectional retrospective database analysis. SETTING: Outpatient clinics within the Department of Veterans Affairs (VA). PARTICIPANTS: Individuals aged 65 and older who received VA outpatient care between October 1, 2003, and September 30, 2006. MEASUREMENTS: Rx-DIS exposure based on the HEDIS measure was identified in VA patients with dementia, falls, and chronic renal failure using VA pharmacy and administrative databases. Factors associated with Rx-DIS exposure were examined, including demographic, health status, and access-to-care factors, including VA outpatient health services use and copayment status. RESULTS: Of the 305,041 older veterans who met criteria for inclusion, the 1-year prevalence of Rx-DIS exposure was 15.2%; prevalence was 20.2% for dementia, 16.2% for falls, and 8.5% for chronic renal failure. Patients with high disease burden (physical, psychiatric, number of medications) were significantly more likely to have Rx-DIS exposure, regardless of condition. Hispanics and individuals with no copayments were more likely to have Rx-DIS exposure than whites or those with required copayments. There was variation in other predictors based on the type of Rx-DIS. CONCLUSION: The prevalence of Rx-DIS was common in older VA outpatients. Future studies should examine the risk of Rx-DIS exposure on health outcomes using separate analyses for each type of Rx-DIS separately before combining all Rx-DIS into a single measure of exposure. Studies that examine the effectiveness of interventions to reduce Rx-DIS exposure will also be helpful in improving the quality of care for older adults. J Am Geriatr Soc 59: 1673-1678, 2011. C1 [Pugh, Mary Jo V.] S Texas Vet Hlth Care Syst, Vet Evidence Based Res & Implementat Ctr, San Antonio, TX 78229 USA. [Horton, Monica] S Texas Vet Hlth Care Syst, Geriatr & Extended Care, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Pugh, Mary Jo V.; Horton, Monica] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Gerontol & Palliat Med, Hlth Sci Ctr, San Antonio, TX 78229 USA. [Starner, Catherine I.] Prime Therapeut, Minneapolis, MN USA. [Amuan, Megan E.; Berlowitz, Dan R.] Edith Nourse Rogers Mem Vet Affairs Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Berlowitz, Dan R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Marcum, Zachary A.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Educ & Clin Ctr, Ctr Hlth Equ Res & Geriatr Res, Pittsburgh, PA USA. RP Pugh, MJV (reprint author), S Texas Vet Hlth Care Syst, Vet Evidence Based Res & Implementat Ctr, VERDICT REAP 11C6,7400 Merton Minter, San Antonio, TX 78229 USA. EM pughm@uthscsa.edu FU VA Health Services Research [IIR-06-062]; National Institute of Aging [R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01NR010135]; Agency for Healthcare Research and Quality [R01HS017695]; Geriatric Academic Career Award [KO1 HP00114-02]; VA Health Services Research and Development Service (HSRD) [IIR 06-062]; VA HSRD [IIR-06-062, DHI 09-237, IIR-06-062 PI, PPO 09-295 PI, IIR 02-274 PI, IIR 08-274, SDR-07-042, IIR-05-121, IAF-06-080, IIR-09-335, SHP 08-140, TRX 01-091, RRP 09-112]; Epilepsy Foundation PI; Department of Defense [CDMRP 09090014]; NIH [R01-NR010828] FX This study was supported by VA Health Services Research Grant IIR-06-062. Dr. Hanlon is supported by National Institute of Aging Grants R01AG027017, P30AG024827, T32 AG021885, K07AG033174, and R01AG034056; National Institute of Mental Health Grant R34 MH082682; National Institute of Nursing Research Grant R01NR010135; and Agency for Healthcare Research and Quality Grant R01HS017695. Dr. Horton is a recipient of Geriatric Academic Career Award KO1 HP00114-02. We acknowledge the contributions of Jeffrey Tabares and Ranjani Davalath in assisting with manuscript preparation.; MJP and MH are employed by the South Texas Veterans Health Care System, DRB and MEA are employed by the Edith Nourse Rogers Memorial VA Hospital, and JTH is employed by the VA Pittsburgh Healthcare System. This study was funded by VA Health Services Research and Development Service (HSR&D) IIR 06-062.; Dr. Pugh has received research funding from VA HSR&D DHI 09-237 (PI); VA HSR&D IIR-06-062 PI, Epilepsy Foundation PI, VA HSR&D PPO 09-295 PI, VA HSR&D IIR 02-274 PI, Pugh as co-investigator: VA HSR&D IIR 08-274, VA HSR&D SDR-07-042, IIR-05-121, IAF-06-080, IIR-09-335, SHP 08-140, TRX 01-091 Department of Defense CDMRP 09090014, NIH R01-NR010828, Pugh Speaker Honoraria: 2009 Kelsey Seybold Research Foundation $400.; Dr. Berlowitz has received funding from VA HSR&D RRP 09-112 as PI, VAHSR&D IIR-06-062 as co-investigator. NR 33 TC 13 Z9 13 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2011 VL 59 IS 9 BP 1673 EP 1678 DI 10.1111/j.1532-5415.2011.03524.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 829WD UT WOS:000295615000014 PM 21831166 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI JULIUS SEYLER AND THE BLACKFEET: An Impressionist at Glacier National Park SO JOURNAL OF THE WEST LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 3 PU ABC-CLIO PI SANTA BARBARA PA 130 CREMONA DR, SANTA BARBARA, CA 93117 USA SN 0022-5169 J9 J WEST JI J. West PD FAL PY 2011 VL 50 IS 4 BP 78 EP 78 PG 1 WC History SC History GA V27OV UT WOS:000208623400019 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI THE FORCED REMOVAL OF AMERICAN INDIANS FROM THE NORTHEAST: A History of Territorial Cessions and Relocations, 1620-1854 SO JOURNAL OF THE WEST LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ABC-CLIO PI SANTA BARBARA PA 130 CREMONA DR, SANTA BARBARA, CA 93117 USA SN 0022-5169 J9 J WEST JI J. West PD FAL PY 2011 VL 50 IS 4 BP 82 EP 82 PG 1 WC History SC History GA V27OV UT WOS:000208623400032 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI ELDORADO! The Archaeology of Gold Mining in the Far North SO JOURNAL OF THE WEST LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ABC-CLIO PI SANTA BARBARA PA 130 CREMONA DR, SANTA BARBARA, CA 93117 USA SN 0022-5169 J9 J WEST JI J. West PD FAL PY 2011 VL 50 IS 4 BP 83 EP 83 PG 1 WC History SC History GA V27OV UT WOS:000208623400036 ER PT J AU Mansour, MK Vyas, JM Levitz, SM AF Mansour, Michael K. Vyas, Jatin M. Levitz, Stuart M. TI Dynamic Virulence: Real-Time Assessment of Intracellular Pathogenesis Links Cryptococcus neoformans Phenotype with Clinical Outcome SO MBIO LA English DT Article ID ASPERGILLUS-FUMIGATUS; VANCOUVER-ISLAND; OUTBREAK AB While a myriad of studies have examined host factors that predispose persons to infection with the opportunistic fungal pathogen Cryptococcus neoformans, comparatively little has been done to examine how virulence factor differences among cryptococcal isolates may impact outcome. In the recent report by Alanio et al. (A. Alanio, M. Desnos-Ollivier, and F. Dromer, mBio 2:e00158-11, 2011), novel flow cytometry-based techniques were employed to demonstrate an association between the phenotype of C. neoformans-macrophage interactions, as measured by phagocytosis and intracellular replication, and patient outcomes, as determined by positive cultures on therapy and survival. These experiments establish that the prognosis of patients with cryptococcosis is influenced by the phenotypic properties of the infecting fungal isolate. C1 [Levitz, Stuart M.] Univ Massachusetts, Med Ctr, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. [Mansour, Michael K.; Vyas, Jatin M.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Levitz, SM (reprint author), Univ Massachusetts, Med Ctr, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. EM stuart.levitz@umassmed.edu RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 FU NIAID, NIH [T32-AI007061-34, 1R01AI092084-01A1, 5R01AI025780-26, 1R21AI093302-01]; MGH Department of Medicine FX M.K.M. is supported by NIAID, NIH (T32-AI007061-34), and in part by internal funds from the MGH Department of Medicine. J.M.V. is supported by NIAID, NIH (1R01AI092084-01A1), and S.M.L. is supported by NIAID, NIH (5R01AI025780-26 and 1R21AI093302-01). NR 9 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD SEP-OCT PY 2011 VL 2 IS 5 AR e00217-11 DI 10.1128/mBio.00217-11 PG 3 WC Microbiology SC Microbiology GA 845SZ UT WOS:000296844300024 ER PT J AU Barnett, PG Chow, A Joyce, VR Bayoumi, AM Griffin, SC Nosyk, B Holodniy, M Brown, ST Sculpher, M Anis, AH Owens, DK AF Barnett, Paul G. Chow, Adam Joyce, Vilija R. Bayoumi, Ahmed M. Griffin, Susan C. Nosyk, Bohdan Holodniy, Mark Brown, Sheldon T. Sculpher, Mark Anis, Aslam H. Owens, Douglas K. CA OPTIMA Team TI Determinants of the Cost of Health Services Used by Veterans With HIV SO MEDICAL CARE LA English DT Article DE HIV; cost; antiretroviral therapy ID ACTIVE ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; MEDICAL-CARE; VIRAL LOAD; EXPENDITURES; MODELS; ERA; VA; PATTERNS; IMPACT AB Background: The effect of adherence, treatment failure, and comorbidities on the cost of HIV care is not well understood. Objective: To characterize the cost of HIV care including combination antiretroviral treatment (ART). Research Design: Observational study of administrative data. Subjects: Total 1896 randomly selected HIV-infected patients and 288 trial participants with multidrug-resistant HIV seen at the US Veterans Health Administration (VHA). Measures: Comorbidities, cost, pharmacy, and laboratory data. Results: Many HIV-infected patients (24.5%) of the random sample did not receive ART. Outpatient pharmacy accounted for 62.8% of the costs of patients highly adherent with ART, 32.2% of the cost of those with lower adherence, and 6.2% of the cost of those not receiving ART. Compared with patients not receiving ART, high adherence was associated with lower hospital cost, but no greater total cost. Individuals with a low CD4 count (<50 cells/mm(3)) incurred 1.9 times the cost of patients with counts >500. Most patients had medical, psychiatric, or substance abuse comorbidities. These conditions were associated with greater cost. Trial participants were less likely to have psychiatric and substance abuse comorbidities than the random sample of VHA patients with HIV. Conclusions: Patients receiving combination ART had higher medication costs but lower acute hospital cost. Poor control of HIV was associated with higher cost. The cost of psychiatric, substance abuse, rehabilitation, and long-term care and medications other than ART, often overlooked in HIV studies, was substantial. C1 [Barnett, Paul G.; Chow, Adam; Joyce, Vilija R.] VA Hlth Econ Resource Ctr, Palo Alto, CA USA. [Bayoumi, Ahmed M.] St Michaels Hosp, Ctr Res Inner City Hlth, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Dept Med & Hlth Policy, Toronto, ON, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Dept Management, Toronto, ON, Canada. [Griffin, Susan C.; Sculpher, Mark] Univ York, Ctr Hlth Econ, York YO10 5DD, N Yorkshire, England. [Nosyk, Bohdan] St Pauls Hosp, Ctr Hlth Evaluat & Outcomes Sci, Vancouver, BC, Canada. [Brown, Sheldon T.] James J Peters VA Med Ctr, Bronx, NY USA. [Anis, Aslam H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Bayoumi, Ahmed M.] Univ Toronto, Dept Evaluat, Toronto, ON, Canada. RP Barnett, PG (reprint author), VA Palo Alto Hlth Care Syst, HERC, 795 Willow Rd,152, Menlo Pk, CA USA. EM paul.barnett@va.gov RI Joyce, Vilija/A-2578-2013 OI Joyce, Vilija/0000-0002-2484-4625 FU US Department of Veterans Affairs; UK Medical Research Council; Canadian Institutes for Health Research FX Funding: US Department of Veterans Affairs Cooperative Studies Program, the UK Medical Research Council, and the Canadian Institutes for Health Research. NR 36 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2011 VL 49 IS 9 BP 848 EP 856 DI 10.1097/MLR.0b013e31821b34c0 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 811JX UT WOS:000294206700015 PM 21610542 ER PT J AU Allen, KD Golightly, YM Helmick, CG Ibrahim, SA Kwoh, CK Renner, JB Jordan, JM AF Allen, K. D. Golightly, Y. M. Helmick, C. G. Ibrahim, S. A. Kwoh, C. K. Renner, J. B. Jordan, J. M. TI RACIAL AND GENDER DIFFERENCES IN WILLINGNESS TO UNDERGO TOTAL JOINT REPLACEMENT: THE JOHNSTON COUNTY OSTEOARTHRITIS PROJECT SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract C1 [Allen, K. D.] Duke Univ, Med Ctr, Durham, NC USA. [Allen, K. D.] Durham VA Med Ctr, Durham, NC USA. [Golightly, Y. M.; Renner, J. B.; Jordan, J. M.] Univ N Carolina, Chapel Hill, NC USA. [Helmick, C. G.] CDC, Atlanta, GA 30333 USA. [Ibrahim, S. A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Ibrahim, S. A.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kwoh, C. K.] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C. K.] Pittsburgh VA Hlth Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2011 VL 19 SU 1 MA 342 BP S155 EP S156 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA V33EH UT WOS:000209001600363 ER PT J AU Katz, JN Wright, EA Baron, JA Malchau, H Mahomed, NN Losina, E AF Katz, J. N. Wright, E. A. Baron, J. A. Malchau, H. Mahomed, N. N. Losina, E. TI RISK FACTORS FOR REVISION OF PRIMARY TOTAL HIP REPLACEMENT: A NATIONAL CASE CONTROL STUDY WITH TWELVE YEAR FOLLOW-UP SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract C1 [Katz, J. N.; Wright, E. A.; Losina, E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Baron, J. A.] Univ N Carolina, Chapel Hill, NC USA. [Malchau, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mahomed, N. N.] Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2011 VL 19 SU 1 MA 96 BP S50 EP S50 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA V33EH UT WOS:000209001600119 ER PT J AU Kwoh, CK Boudreau, R Guermazi, A Hannon, MJ Green, SM Jakicic, JM Moore, C Roemer, FW AF Kwoh, C. K. Boudreau, R. Guermazi, A. Hannon, M. J. Green, S. M. Jakicic, J. M. Moore, C. Roemer, F. W. TI IDENTIFICATION OF MRI MORPHOLOGIC FEATURES ASSOCIATED WITH DIFFERENT KNEE PAIN PATTERNS SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract C1 [Kwoh, C. K.] Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [Boudreau, R.; Hannon, M. J.; Green, S. M.; Jakicic, J. M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Guermazi, A.] Boston Univ, Sch Med, Quantitat Imaging Ctr, Boston, MA 02118 USA. [Moore, C.] Texas Womans Univ, Houston, TX USA. [Roemer, F. W.] Klinikum Augsburg, Augsburg, Germany. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2011 VL 19 SU 1 MA 12 BP S12 EP S13 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA V33EH UT WOS:000209001600035 ER PT J AU Lo, GH McAlindon, TE AF Lo, G. H. McAlindon, T. E. TI KNEE ALIGNMENT MAY INFLUENCE PERI-ARTICULAR BONE MORPHOLOGY SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract C1 [Lo, G. H.] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. [Lo, G. H.] Baylor Coll Med, Houston, TX 77030 USA. [McAlindon, T. E.] Tufts Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1063-4584 EI 1522-9653 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD SEP PY 2011 VL 19 SU 1 MA 95 BP S49 EP S50 PG 2 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA V33EH UT WOS:000209001600118 ER PT J AU Thomas, D Blay, JY Chawla, S Broto, JM Choy, E Dominkus, M Engellau, J Grimer, R Henshaw, R Palmerini, E Reichardt, P Rutkowski, P Skubitz, K Zhao, Y Qian, Y Jacobs, I AF Thomas, D. Blay, J. Y. Chawla, S. Broto, J. M. Choy, E. Dominkus, M. Engellau, J. Grimer, R. Henshaw, R. Palmerini, E. Reichardt, P. Rutkowski, P. Skubitz, K. Zhao, Y. Qian, Y. Jacobs, I. TI SAFETY AND EFFICACY OF DENOSUMAB IN GIANT CELL TUMOUR OF BONE (GCTB) SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT IOF Regionals 2nd Asia-Pacific Osteoporosis and Bone Meeting / ANZBMS Annual Scientific Meeting held with the JSBMR CY SEP 04-08, 2011 CL Gold Coast, AUSTRALIA SP ANZBMS, JSBMR, IOF Reg C1 [Thomas, D.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Blay, J. Y.] Ctr Leon Berard, Dept Med, F-69373 Lyon, France. [Chawla, S.] Sarcoma Oncol Ctr, Santa Monica, CA USA. [Broto, J. M.] Hosp Son Dureta, Palma De Mallorca, Spain. [Choy, E.] Massachusetts Gen Hosp, Dana Farber Harvard Canc Ctr, Boston, MA 02114 USA. [Dominkus, M.] Med Univ Wien, Vienna, Austria. [Engellau, J.] Skane Univ Sjukhus, Lund, Sweden. [Grimer, R.] Royal Orthopaed Hosp, Birmingham B31 2AP, W Midlands, England. [Henshaw, R.] Georgetown Univ, Coll Med, Washington, DC USA. [Palmerini, E.] Ist Ortoped Rizzoli, Bologna, Italy. [Reichardt, P.] HELIOS Klin Bad Saarow, Bad Saarow Pieskow, Germany. [Rutkowski, P.] Mem Canc Ctr, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. [Rutkowski, P.] Inst Oncol, Warsaw, Poland. [Skubitz, K.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Zhao, Y.; Qian, Y.; Jacobs, I.] Amgen Inc, Thousand Oaks, CA 91320 USA. RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD SEP PY 2011 VL 22 SU 4 MA 115 BP S558 EP S558 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 012SZ UT WOS:000309258200116 ER PT J AU Glasgow, R Emmons, KM AF Glasgow, Russ Emmons, Karen M. TI The public health need for patient-reported measures and health behaviors in electronic health records: a policy statement of the Society of Behavioral Medicine (vol 1, pg 108, 2011) SO TRANSLATIONAL BEHAVIORAL MEDICINE LA English DT Correction C1 [Glasgow, Russ] Kaiser Permanente Colorado, Denver, CO USA. [Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Emmons, KM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,LW601, Boston, MA 02215 USA. EM karen_m_emmons@dfci.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1869-6716 EI 1613-9860 J9 TRANSL BEHAV MED JI Transl. Behav. Med. PD SEP PY 2011 VL 1 IS 3 BP 400 EP 400 DI 10.1007/s13142-011-0042-2 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V39LI UT WOS:000209412100008 ER PT J AU Bao, Y Nimptsch, K Wolpin, BM Michaud, DS Brand-Miller, JC Willett, WC Giovannucci, E Fuchs, CS AF Bao, Ying Nimptsch, Katharina Wolpin, Brian M. Michaud, Dominique S. Brand-Miller, Jennie C. Willett, Walter C. Giovannucci, Edward Fuchs, Charles S. TI Dietary insulin load, dietary insulin index, and risk of pancreatic cancer SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID SUGAR-SWEETENED FOODS; GLYCEMIC LOAD; MALE SMOKERS; COHORT; QUESTIONNAIRE; METAANALYSIS; CONSUMPTION; WOMEN AB Background: Although hyperinsulinemia and insulin resistance have been hypothesized to be involved in pancreatic carcinogenesis, studies that have examined glycemic load or individual dietary components that influence glucose concentrations yielded inconclusive results. Objective: Our objective was to investigate whether dietary insulin load and dietary insulin index are associated with the risk of pancreatic cancer. Design: We prospectively followed 86,740 women and 46,147 men who were free of cancer and diabetes at baseline in the Nurses' Health Study and the Health Professionals Follow-Up Study. During <= 26 y of follow-up, 691 pancreatic cancer cases were documented. Dietary insulin load was calculated as a function of the food insulin index, and the energy content of individual foods was reported on food-frequency questionnaires. The dietary insulin index was calculated by dividing the dietary insulin load by the total energy intake. Results: Dietary insulin load and dietary insulin index were not associated with the overall risk of pancreatic cancer. In a comparison of the highest with the lowest quintiles, the pooled multivariate RRs of pancreatic cancer were 1.05 (95% CI: 0.82, 1.34) for dietary insulin load and 0.96 (95% CI: 0.75, 1.23) for dietary insulin index. In individuals with an elevated BMI (in kg/m(2); >= 27.5) or with low physical activity, a high insulin load was associated with small, nonsignificant increases in the risk of pancreatic cancer; in a comparison of the highest with the lowest tertile of intake, the positive association became more apparent in those who were both overweight and inactive (RR: 2.03; 95% CI: 1.05, 3.93; P-trend = 0.04). Conclusions: A diet that induces an elevated postprandial insulin response does not influence the overall risk of pancreatic cancer. However, a diet with a high insulin load may increase the risk in individuals with a preexisting state of insulin resistance. Am J Clin Nutr 2011;94:862-8. C1 [Bao, Ying; Giovannucci, Edward; Fuchs, Charles S.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Bao, Ying; Giovannucci, Edward; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Michaud, Dominique S.; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Nimptsch, Katharina; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London SW7 2AZ, England. [Brand-Miller, Jennie C.] Univ Sydney, Inst Obes Nutr & Exercise, Sydney, NSW 2006, Australia. RP Bao, Y (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM ying.bao@channing.harvard.edu RI Brand-Miller, Jennie/A-6835-2013; Michaud, Dominique/I-5231-2014; OI Brand-Miller, Jennie/0000-0002-6797-8754; Nimptsch, Katharina/0000-0001-7877-205X FU NIH [CA124908] FX Supported by grants from the NIH (CA124908). NR 27 TC 6 Z9 7 U1 0 U2 7 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 2011 VL 94 IS 3 BP 862 EP 868 DI 10.3945/ajcn.110.011205 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 809IX UT WOS:000294047200022 PM 21775564 ER PT J AU Shlipak, MG Coca, SG Wang, Z Devarajan, P Koyner, JL Patel, UD Thiessen-Philbrook, H Garg, AX Parikh, CR AF Shlipak, Michael G. Coca, Steven G. Wang, Zhu Devarajan, Prasad Koyner, Jay L. Patel, Uptal D. Thiessen-Philbrook, Heather Garg, Amit X. Parikh, Chirag R. CA TRIBE-AKI Consortium TI Presurgical Serum Cystatin C and Risk of Acute Kidney Injury After Cardiac Surgery SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Acute renal failure; creatinine; prognosis ID ACUTE-RENAL-FAILURE; ELDERLY PERSONS; HOSPITALIZED-PATIENTS; SURGICAL-PATIENTS; ROC CURVE; MORTALITY; BYPASS; RECLASSIFICATION; STRATIFICATION; MORBIDITY AB Background: Acute kidney injury (AKI) after cardiac surgery is associated with poor outcomes, but is challenging to predict from information available before surgery. Study Design: Prospective cohort study. Setting & Participants: The TRIBE-AKI (Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury) Consortium enrolled 1,147 adults undergoing cardiac surgery at 6 hospitals from 2007-2009; participants were selected for high AKI risk. Predictors: Presurgical values for cystatin C, creatinine, and creatinine-based estimated glomerular filtration rate (eGFR) were categorized into quintiles and grouped as "best" (quintiles 1-2), "intermediate" (quintiles 3-4), and "worst" (quintile 5) kidney function. Outcomes: The primary outcome was AKI Network (AKIN) stage 1 or higher; >= 0.3 mg/dL or 50% increase in creatinine level. Measurements: Analyses were adjusted for characteristics used clinically for presurgical risk stratification. Results: Average age was 71 +/- 10 years (mean +/- standard deviation); serum creatinine, 1.1 +/- 0.3 mg/dL; eGFR-Cr, 74 +/- 9 mL/min/1.73 m(2); and cystatin C, 0.9 +/- 0.3 mg/L. 407 (36%) participants developed AKI during hospitalization. Adjusted odds ratios for intermediate and worst kidney function by cystatin C were 1.9 (95% CI, 1.4-2.7) and 4.8 (95% CI, 2.9-7.7) compared with 1.2 (95% CI, 0.9-1.7) and 1.8 (95% CI, 1.2-2.6) for creatinine and 1.0 (95% CI, 0.7-1.4) and 1.7 (95% CI, 1.1-2.3) for eGFR-Cr categories, respectively. After adjustment for clinical predictors, the C statistic to predict AKI was 0.70 without kidney markers, 0.69 with creatinine, and 0.72 with cystatin C. Cystatin C also substantially improved AKI risk classification compared with creatinine, based on a net reclassification index of 0.21 (P < 0.001). Limitations: The ability of these kidney biomarkers to predict risk of dialysis-requiring AKI or death could not be assessed reliably in our study because of a small number of patients with either outcome. Conclusions: Presurgical cystatin C is better than creatinine or creatinine-based eGFR at forecasting the risk of AKI after cardiac surgery. Am J Kidney Dis. 58(3): 366-373. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Coca, Steven G.; Wang, Zhu; Parikh, Chirag R.] Yale Univ, Nephrol Sect, West Haven, CT 06516 USA. [Coca, Steven G.; Wang, Zhu; Parikh, Chirag R.] VAMC, West Haven, CT 06516 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Devarajan, Prasad] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Koyner, Jay L.] Univ Chicago, Pritzker Sch Med, Dept Med, Nephrol Sect, Chicago, IL 60637 USA. [Patel, Uptal D.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Div Nephrol, Dept Med, London, ON, Canada. [Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Div Nephrol, Dept Epidemiol, London, ON, Canada. [Thiessen-Philbrook, Heather; Garg, Amit X.] Univ Western Ontario, Div Nephrol, Dept Biostat, London, ON, Canada. RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, 950 Campbell Ave,Mail Code 151B,Bldg 35A,Rm 219, West Haven, CT 06516 USA. EM chirag.parikh@yale.edu FU American Heart Association; National Heart, Lung, and Blood Institute [RO1HL-085757]; National Center for Research Resources [UL1 RR024139] FX The research reported in this article was supported by the American Heart Association Clinical Development award and grant RO1HL-085757 from the National Heart, Lung, and Blood Institute. The study was also supported by Clinical Translational Science Award grant number UL1 RR024139 from the National Center for Research Resources. The granting agencies did not participate in the protocol development, analysis, and interpretation of the results. NR 29 TC 35 Z9 36 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2011 VL 58 IS 3 BP 366 EP 373 DI 10.1053/j.ajkd.2011.03.015 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 809KW UT WOS:000294055100009 PM 21601336 ER PT J AU Kraut, JA Xing, SX AF Kraut, Jeffrey A. Xing, Shelly Xiaolei TI Approach to the Evaluation of a Patient With an Increased Serum Osmolal Gap and High-Anion-Gap Metabolic Acidosis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE High-anion-gap metabolic acidosis; serum osmolality; osmolal gap; ketoacidosis; methanol; ethylene glycol; diethylene glycol; propylene glycol; isopropanol ID ETHYLENE-GLYCOL; ALCOHOLIC KETOACIDOSIS; ETHANOL INGESTION; METHANOL; DIAGNOSIS; INTOXICATIONS AB An increase in serum osmolality and serum osmolal gap with or without high-anion-gap metabolic acidosis is an important clue to exposure to one of the toxic alcohols, which include methanol, ethylene glycol, diethylene glycol, propylene glycol, or isopropanol. However, the increase in serum osmolal gap and metabolic acidosis can occur either together or alone depending on several factors, including baseline serum osmolal gap, molecular weight of the alcohol, and stage of metabolism of the alcohol. In addition, other disorders, including diabetic or alcoholic ketoacidosis, acute kidney injury, chronic kidney disease, and lactic acidosis, can cause high-anion-gap metabolic acidosis associated with an increased serum osmolal gap and therefore should be explored in the differential diagnosis. It is essential for clinicians to understand the value and limitations of osmolal gap to assist in reaching the correct diagnosis and initiating appropriate treatment. In this teaching case, we present a systematic approach to diagnosing high serum osmolality and increased serum osmolal gap with or without high-anion-gap metabolic acidosis. Am J Kidney Dis. 58(3): 480-484. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Kraut, Jeffrey A.; Xing, Shelly Xiaolei] VHAGLA Healthcare Syst, Div Nephrol, Los Angeles, CA 90073 USA. [Kraut, Jeffrey A.; Xing, Shelly Xiaolei] Vet Adm Greater Los Angeles VHAGLA Healthcare Sys, Med Serv, Los Angeles, CA USA. [Kraut, Jeffrey A.; Xing, Shelly Xiaolei] Vet Adm Greater Los Angeles VHAGLA Healthcare Sys, Res Serv, Los Angeles, CA USA. [Kraut, Jeffrey A.] UCLA Membrane Biol Lab, Los Angeles, CA USA. [Kraut, Jeffrey A.] UCLA David Geffen Sch Med Sci Los Angeles, Los Angeles, CA USA. RP Kraut, JA (reprint author), VHAGLA Healthcare Syst, Div Nephrol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkraut@ucla.edu FU Veterans Administration FX This work was supported in part by research funds provided by the Veterans Administration. NR 27 TC 11 Z9 11 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2011 VL 58 IS 3 BP 480 EP 484 DI 10.1053/j.ajkd.2011.05.018 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 809KW UT WOS:000294055100023 PM 21794966 ER PT J AU Misdraji, J Harris, NL Hasserjian, RP Lauwers, GY Ferry, JA AF Misdraji, Joseph Harris, Nancy Lee Hasserjian, Robert P. Lauwers, Gregory Y. Ferry, Judith A. TI Primary Follicular Lymphoma of the Gastrointestinal Tract SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE follicular lymphoma; gastrointestinal tract; small intestine; duodenum ID MANTLE CELL LYMPHOMA; SMALL-INTESTINE; MALIGNANT-LYMPHOMA; PATHOLOGICAL FEATURES; CASE SERIES; INVOLVEMENT; ENDOSCOPY; POLYPOSIS; DISTINCT AB Background: Follicular lymphoma (FL), a common nodal lymphoma, is rare in the gastrointestinal (GI) tract. We report our experience with primary FL of the GI tract. Methods: The surgical pathology computer files at the Massachusetts General Hospital were searched for cases of FL involving the GI tract. Patients were included if on staging, the major site of disease was the GI tract. Thirty-nine cases were identified. Clinical data were collected from electronic medical records. Results: The 27 women and 12 men ranged in age from 29 to 79 years (median, 59 y). Thirty tumors involved the small bowel (19 the duodenum); 8 involved the colon; and 1 involved the stomach. Eight of 10 tumors that were resected involved the small bowel (jejunum and/or ileum without duodenum) of which 5 presented with intestinal obstruction. All tumors were grade 1 or 2. Immunostains showed consistent expression of CD20 (100%), CD10 (97%), and Bcl-2 (97%). Among the 34 cases with Ann Arbor staging information, 22 were stage I, 10 were stage II, and 2 were (6%) stage IV. Of 36 cases with follow-up (median, 4.5 y), 27 patients are alive without disease, 7 are alive with disease, and 2 died of other causes. No lymphoma-related deaths were recorded. Conclusions: Primary FL of the GI tract occurs most often in middle-aged adults with a 2: 1 female preponderance. The most frequent site of involvement is the duodenum, followed by the ileum and colon. Distal small bowel involvement is more likely to present as bowel obstruction requiring resection. The disease is localized in the bowel and regional lymph nodes in the vast majority of cases. The prognosis is favorable even when the disease is disseminated. C1 [Misdraji, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs,Dept Pathol, Boston, MA 02114 USA. RP Misdraji, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs,Dept Pathol, Warren Bldg 105F, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 35 TC 17 Z9 21 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2011 VL 35 IS 9 BP 1255 EP 1263 DI 10.1097/PAS.0b013e318224e661 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 806TG UT WOS:000293834400001 PM 21836483 ER PT J AU Chiang, S Ali, R Melnyk, N McAlpine, JN Huntsman, DG Gilks, CB Lee, CH Oliva, E AF Chiang, Sarah Ali, Rola Melnyk, Nataliya McAlpine, Jessica N. Huntsman, David G. Gilks, C. Blake Lee, Cheng-Han Oliva, Esther TI Frequency of Known Gene Rearrangements in Endometrial Stromal Tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometrial stromal tumor; uterine/extrauterine endometrial stromal sarcoma; molecular pathogenesis; translocation; gene fusion ID SMOOTH-MUSCLE TUMORS; IN-SITU HYBRIDIZATION; HIGH-GRADE SARCOMAS; OF-THE-LITERATURE; GLANDULAR DIFFERENTIATION; MOLECULAR ANALYSIS; UTERINE SARCOMAS; H-CALDESMON; CELL-LINE; RT-PCR AB Translocations resulting in gene fusion are characteristic of endometrial stromal tumors (ESTs). Rearrangements of JAZF1, SUZ12, PHF1, and EPC1 have been reported in endometrial stromal nodules (ESNs), endometrial stromal sarcomas (ESSs), and rarely in undifferentiated endometrial sarcomas (UESs). Detection of JAZF1, SUZ12, EPC1, and PHF1 rearrangement by fluorescence in situ hybridization was performed on tissue microarrays consisting of 94 ESTs of classic and variant morphology (20 ESNs, 43 primary uterine ESSs, 15 metastatic uterine ESSs, 4 primary extrauterine ESSs, 7 primary uterine UESs, and 5 unclassified ESTs), 16 Mullerian adenosarcomas, 2 malignant mixed Mullerian tumors, 2 uterine tumors resembling ovarian sex-cord tumors, 2 highly cellular leiomyomas, 1 leiomyosarcoma, and 7 polypoid endometriosis. Rearrangements were detected in 42 of 78 (54%) uterine ESTs, with JAZF1-SUZ12 fusion found in 50% of ESNs and in 33% of ESSs and JAZF1-PHF1 and EPC1-PHF1 fusions found in 1% and < 1% of ESSs, respectively. PHF1 and JAZF1 were rearranged with unknown partners in 8 uterine ESTs. JAZF1-SUZ12 fusion, EPC1-PHF1 fusion, and PHF1 rearrangement were found in 3 extrauterine ESSs, whereas no rearrangements were observed in UESs or in any other non-EST studied. Our data confirm that gene rearrangements are present in more than 50% of uterine ESTs, with JAZF1-SUZ12 fusion being the most common, followed by rare EPC1-PHF1 and JAZF1-PHF1 fusions. The presence of identical gene rearrangements in both uterine and extrauterine ESTs suggests a similar pathogenesis. The presence of detectable gene rearrangements in uterine ESS may predict better patient outcome. C1 [Chiang, Sarah; Oliva, Esther] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ali, Rola; Melnyk, Nataliya; Huntsman, David G.; Gilks, C. Blake; Lee, Cheng-Han] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [McAlpine, Jessica N.] Univ British Columbia, Dept Obstet & Gynaecol, Vancouver, BC V5Z 1M9, Canada. RP Oliva, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 2, Boston, MA 02114 USA. EM eoliva@partners.org OI Ali, Rola/0000-0001-5747-8900 NR 76 TC 41 Z9 41 U1 0 U2 3 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 SEP PY 2011 VL 35 IS 9 BP 1364 EP 1372 DI 10.1097/PAS.0b013e3182262743 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 806TG UT WOS:000293834400014 PM 21836477 ER PT J AU Lisovsky, M Konstas, AA Misdraji, J AF Lisovsky, Mikhail Konstas, Angelos A. Misdraji, Joseph TI Congenital Extrahepatic Portosystemic Shunts (Abernethy Malformation): A Histopathologic Evaluation SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Abernethy malformation; congenital portosystemic shunt; portal vein; hepatocellular carcinoma ID NODULAR REGENERATIVE HYPERPLASIA; IDIOPATHIC PORTAL-HYPERTENSION; HEPATOCELLULAR-CARCINOMA; LIVER-TRANSPLANTATION; PORTACAVAL-SHUNT; ADULT WOMAN; VEIN; ABSENCE; PATHOGENESIS; PATIENT AB Congenital extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare malformation in which intestinal and splenic venous blood bypasses the liver and drains into systemic veins. Aside from the complete or near-complete absence of portal veins, other histologic features of Abernethy malformation have not been evaluated in the literature. The goal of this study was to detail the hepatic histopathology in 5 patients with Abernethy malformation diagnosed at our institution. Paraffin-embedded tissue sections from 1 explant, 2 liver tumor resections, and 2 liver biopsies were evaluated using hematoxylin and eosin stains, reticulin, elastic, and trichrome stains, and immunohistochemistry for D2-40. Histologic findings included absence of portal veins in small portal tracts, absent or hypoplastic portal veins in medium-sized and large-sized portal tracts, isolated capillaries and arterioles in the lobules, hypertrophy of hepatic artery branches, remodeling of the liver architecture, and nodular regenerative hyperplasia in 1 case. Two patients had hepatocellular carcinoma without cirrhosis, and 2 had focal nodular hyperplasia. In addition to loss of portal veins, Abernethy malformation is characterized by multiple abnormalities due to remodeling of the hepatic vasculature. Abernethy malformation may also be associated with hepatocellular carcinoma and focal nodular hyperplasia in some patients. C1 [Misdraji, Joseph] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Lisovsky, Mikhail] Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. [Konstas, Angelos A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Misdraji, J (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 55 Fruit St,Warren Bldg 105F, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 60 TC 15 Z9 16 U1 0 U2 3 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 SEP PY 2011 VL 35 IS 9 BP 1381 EP 1390 DI 10.1097/PAS.0b013e3182230ce4 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 806TG UT WOS:000293834400016 PM 21836489 ER PT J AU Meszaros, ZS Dimmock, JA Ploutz-Snyder, RJ Abdul-Malak, Y Leontieva, L Canfield, K Batki, SL AF Meszaros, Zsuzsa Szombathyne Dimmock, Jacqueline A. Ploutz-Snyder, Robert J. Abdul-Malak, Ynesse Leontieva, Luba Canfield, Kelly Batki, Steven L. TI Predictors of Smoking Severity in Patients with Schizophrenia and Alcohol Use Disorders SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID PSYCHIATRIC-DISORDERS; CIGARETTE-SMOKING; TOBACCO USE; DEPRESSION; CESSATION; SCALE; COMORBIDITY; MEDICATION; DEPENDENCE; BEHAVIORS AB The goal of the present study was to identify predictors of smoking severity in patients with schizophrenia and co-occurring alcohol use disorders (AUD). Our hypothesis was that negative symptoms of schizophrenia, severity of depression, male gender, drinking severity, and recreational drug use were associated with increased smoking. Clinical data, including demographic variables, alcohol and substance use severity, psychiatric medications, severity of depression, positive and negative symptoms of schizophrenia were analyzed in a cohort of 90 patients with schizophrenia or schizoaffective disorder and AUD. Eighty-eight percent of participants were smokers, they smoked an average of 15 cigarettes/day. Zero-inflated negative binomial (ZINB) regression analyses demonstrated that alcohol use severity, gender, and severity of negative symptoms were not predictive of the number of cigarettes smoked. Smoking severity was positively related to Caucasian race, psychosis severity (Positive and Negative Syndrome Scale [PANSS] general score), and medications (conventional antipsychotics). Subjects who used recreational drugs smoked less. In summary, severe, treatment resistant schizophrenia, and conventional antipsychotic treatment is associated with heavy smoking in patients with schizophrenia and AUD regardless of gender or alcohol use. (Am J Addict 2011; 20: 462-467) C1 [Meszaros, Zsuzsa Szombathyne; Dimmock, Jacqueline A.; Abdul-Malak, Ynesse; Leontieva, Luba; Canfield, Kelly; Batki, Steven L.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Ploutz-Snyder, Robert J.] Univ Space Res Assoc, Space Life Sci Div, Houston, TX USA. [Ploutz-Snyder, Robert J.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY USA. [Batki, Steven L.] UCSF Dept Psychiat, San Francisco, CA USA. [Batki, Steven L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Meszaros, ZS (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM meszaroz@upstate.edu FU NIAAA NIH HHS [R01 AA013655-01A1, R01 AA013655] NR 33 TC 10 Z9 10 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 EI 1521-0391 J9 AM J ADDICTION JI Am. J. Addict. PD SEP-OCT PY 2011 VL 20 IS 5 BP 462 EP 467 DI 10.1111/j.1521-0391.2011.00150.x PG 6 WC Substance Abuse SC Substance Abuse GA 807FO UT WOS:000293881900010 PM 21838846 ER PT J AU Bausch, D Pausch, T Krauss, T Hopt, UT Fernandez-del-Castillo, C Warshaw, AL Thayer, SP Keck, T AF Bausch, Dirk Pausch, Thomas Krauss, Tobias Hopt, Ulrich Theodor Fernandez-del-Castillo, Carlos Warshaw, Andrew L. Thayer, Sarah P. Keck, Tobias TI Neutrophil granulocyte derived MMP-9 is a VEGF independent functional component of the angiogenic switch in pancreatic ductal adenocarcinoma SO ANGIOGENESIS LA English DT Article DE VEGF; MMP-9; Neutrophil granulocyte; Pancreatic cancer ID ENDOTHELIAL GROWTH-FACTOR; MATRIX-METALLOPROTEINASE INHIBITION; PHASE-II TRIAL; TUMOR ANGIOGENESIS; CELL-MIGRATION; STROMAL METALLOPROTEINASE-9; COMBINATION THERAPY; HEMOPEXIN DOMAIN; FACTOR BLOCKADE; LINE THERAPY AB Vascular endothelial growth factor (VEGF) that is secreted by tumor cells plays a key role in angiogenesis. Matrix metalloproteinase 9 (MMP-9) is produced by inflammatory cells, such as stromal granulocytes (PMN), remodels the extracellular matrix and is known to promote angiogenesis indirectly by interacting with VEGF. The aim of this study was to determine the role of PMN-derived MMP-9, its interaction with VEGF, and the efficacy of anti-angiogenic therapy targeting MMP-9 with oral Doxycycline and VEGF with Bevacizumab in pancreatic cancer (PDAC). Inhibitors to MMP-9 (Doxycycline) and VEGF (Bevacizumab) were used alone or in combination in an in vitro angiogenesis assay to test their effect on angiogenesis caused by MMP-9, VEGF, PMN and PDAC cells. In an in vivo model of xenografted PDAC, treatment effects after 14 days under monotherapy with oral Doxycycline or Bevacizumab and a combination of both were evaluated. In vitro, PMN-derived MMP-9 had a direct and strong proangiogenic effect that was independent and additive to PDAC-derived VEGF. Complete inhibition of angiogenesis required the inhibition of VEGF and MMP-9. In vivo, co-localization of MMP-9, PMN and vasculature was observed. MMP inhibition with oral Doxycycline alone resulted in a significant decrease in PDAC growth and mean vascular density comparable to VEGF inhibition alone. PMN derived MMP-9 acts as a potent, direct and VEGF independent angiogenic factor in the context of PDAC. MMP-9 inhibition is as effective as VEGF inhibition. Targeting MMP-9 in addition to VEGF is therefore likely to be important for successful anti-angiogenic treatment in pancreatic cancer. C1 [Bausch, Dirk; Hopt, Ulrich Theodor; Keck, Tobias] Univ Freiburg, Dept Gen & Visceral Surg, D-79106 Freiburg, Germany. [Pausch, Thomas] Univ Heidelberg, Klin Allgemein Viszeral & Transplantat Chirurg, D-69120 Heidelberg, Germany. [Krauss, Tobias] Radiol Univ Klin Freiburg Br, D-79106 Freiburg, Germany. [Fernandez-del-Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Fernandez-del-Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Keck, T (reprint author), Univ Freiburg, Dept Gen & Visceral Surg, Hugstetter Str 55, D-79106 Freiburg, Germany. EM Tobias.Keck@uniklinik-freiburg.de FU NCI NIH HHS [P01 CA117969, P01 CA117969-03, P01 CA117969-04, P01 CA117969-04S1, P50 CA127003, P50 CA127003-03]; NIDDK NIH HHS [K08 DK071329, K08 DK071329-04, K08 DK071329-05] NR 43 TC 36 Z9 38 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD SEP PY 2011 VL 14 IS 3 BP 235 EP 243 DI 10.1007/s10456-011-9207-3 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 807TJ UT WOS:000293922300002 PM 21442180 ER PT J AU Zhang, HK Lerwill, M AF Zhang, Hongkai Lerwill, Melinda TI Co-existence of three rare gynecological tumors in a 79-year-old woman SO ARCHIVES OF GYNECOLOGY AND OBSTETRICS LA English DT Article DE Myxoid leiomyosarcoma; Endometrial mucinous adenocarcinoma; Leydig cell tumor; Uterus Ovary ID FEMALE GENITAL-TRACT; LEYDIG-CELL TUMOR; MYXOID LEIOMYOSARCOMA; UTERUS; OVARY; VIRILIZATION; ENDOMETRIAL; NEOPLASMS; PATIENT AB The occurrence of two primary tumors simultaneously is relatively common. However, the occurrence of three kinds of gynecological tumors simultaneously is extremely rare. Here we presented a 79-year-old woman who had simultaneously three primary gynecological tumors which were relatively uncommon. Those tumors were myxoid leiomyosarcoma and endometrial mucinous adenocarcinoma in the uterus and a Leydig cell tumor in the right ovary. Uterine myxoid leiomyosarcoma is a very rare and aggressive variant of uterine sarcoma despite of its minimal even no atypia and a little mitotic activity. Mucinous endometrial adenocarcinoma is also a rare subtype which comprise only 0.6-5% of uterine cancers. Leydig cell tumor is a very rare ovarian tumor which is composed entirely or predominantly of Leydig cell. C1 [Zhang, Hongkai] Capital Univ Med Sci, Dept Pathol, Beijing Fuxing Hosp, Beijing 100038, Peoples R China. [Lerwill, Melinda] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Zhang, HK (reprint author), Capital Univ Med Sci, Dept Pathol, Beijing Fuxing Hosp, Beijing Fuxing Menwai St 20, Beijing 100038, Peoples R China. EM zhk0484@sina.com.cn NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0932-0067 J9 ARCH GYNECOL OBSTET JI Arch. Gynecol. Obstet. PD SEP PY 2011 VL 284 IS 3 BP 695 EP 698 DI 10.1007/s00404-010-1688-6 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 807TQ UT WOS:000293923100030 PM 20886347 ER PT J AU Gallagher, CL Johnson, SC Bendlin, BB Chung, MK Holden, JE Oakes, TR Brooks, BR Konopacki, RA Dogan, S Abbs, JH Xu, GF Nickles, RJ Pyzalski, RW DeJesus, OT Brown, WD AF Gallagher, Catherine L. Johnson, Sterling C. Bendlin, Barbara B. Chung, Moo K. Holden, James E. Oakes, Terrence R. Brooks, Benjamin R. Konopacki, Richard A. Dogan, Selami Abbs, James H. Xu, Guofan Nickles, Robert J. Pyzalski, Robert W. DeJesus, Onofre T. Brown, W. Douglas TI A longitudinal study of motor performance and striatal [18F]fluorodopa uptake in Parkinson's disease SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Fluorodopa; Motor control; Parkinson's disease; Positron emission tomography; Ageing; Tongue/*physiopathology; Facial Muscles/*physiopathology ID REACTION-TIME; BASAL GANGLIA; MOVEMENT; PROGRESSION; DOPAMINE; FORCE; ONSET; PET; ABNORMALITIES; BRADYKINESIA AB Although [F-18]fluoro-l-dopa [FDOPA] positron emission tomography (PET) has been used as a surrogate outcome measure in Parkinson's disease therapeutic trials, this biomarker has not been proven to reflect clinical status longitudinally. We completed a retrospective analysis of relationships between computerized sampling of motor performance, FDOPA PET, and clinical outcome scales, repeated over 4 years, in 26 Parkinson's disease (PD) patients and 11 healthy controls. Mixed effects analyses showed that movement time and tongue strength best differentiated PD from control subjects. In the treated PD cohort, motor performance measures changed gradually in contrast to a steady decline in striatal FDOPA uptake. Prolonged reaction and movement time were related to lower caudate nucleus FDOPA uptake, and abnormalities in hand fine force control were related to mean striatal FDOPA uptake. These findings provide evidence that regional loss of nigrostriatal inputs to frontostriatal networks affects specific aspects of motor function. C1 [Gallagher, Catherine L.; Abbs, James H.] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Johnson, Sterling C.; Bendlin, Barbara B.; Xu, Guofan] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53792 USA. [Johnson, Sterling C.; Bendlin, Barbara B.; Xu, Guofan] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Chung, Moo K.; Konopacki, Richard A.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. [Chung, Moo K.; Oakes, Terrence R.] Waisman Ctr Brain Imaging & Behav, Madison, WI USA. [Holden, James E.; Nickles, Robert J.; DeJesus, Onofre T.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Brooks, Benjamin R.] Carolinas Neuromuscular ALS MDA Ctr, Charlotte, NC USA. [Dogan, Selami] Aurora Sinai Med Ctr, Milwaukee, WI USA. [Pyzalski, Robert W.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. [Brown, W. Douglas] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. RP Gallagher, CL (reprint author), Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM gallagher@neurology.wisc.edu OI Bendlin, Barbara/0000-0002-0580-9875; Johnson, Sterling/0000-0002-8501-545X FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Science Research and Development Service; National Institutes of Health [1R29NS31612]; University of Wisconsin Institute for Clinical and Translational Research through National Institutes of Health [1UL1RR025011] FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Science Research and Development Service [grant to C.G]; National Institutes of Health [grant number 1R29NS31612 to D.B] and University of Wisconsin Institute for Clinical and Translational Research, funded through a National Institutes of Health Clinical and Translational Science Award, [grant number 1UL1RR025011 to C.G.]. NR 47 TC 4 Z9 4 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD SEP PY 2011 VL 5 IS 3 BP 203 EP 211 DI 10.1007/s11682-011-9124-5 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA 802GY UT WOS:000293498500005 PM 21556744 ER PT J AU Medverd, JR Ngo, AV Bhargava, P AF Medverd, J. R. Ngo, A-V Bhargava, P. TI An unusual cause of persistent subcutaneous fluid collection SO BRITISH JOURNAL OF RADIOLOGY LA English DT Editorial Material ID MOREL-LAVALLEE LESION; DEGLOVING INJURIES; MANAGEMENT C1 [Medverd, J. R.; Ngo, A-V; Bhargava, P.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Medverd, J. R.; Bhargava, P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Medverd, JR (reprint author), VA Puget Sound Hlth Care Ctr, Mail Box 358280,S-114-RAD,1660 S Columbian Way, Seattle, WA 98108 USA. EM jmed@u.washington.edu RI Bhargava, Puneet /F-1330-2011; OI Bhargava, Puneet/0000-0002-3849-9666 NR 9 TC 3 Z9 3 U1 0 U2 3 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD SEP PY 2011 VL 84 IS 1005 BP 864 EP 866 DI 10.1259/bjr/29764457 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 807ZY UT WOS:000293943400022 PM 21849371 ER PT J AU de Paula, FJA Dick-de-Paula, I Bornstein, S Rostama, B Le, P Lotinun, S Baron, R Rosen, CJ AF de Paula, Francisco J. A. Dick-de-Paula, Ingrid Bornstein, Sheila Rostama, Bahman Le, Phuong Lotinun, Sutada Baron, Roland Rosen, Clifford J. TI VDR Haploinsufficiency Impacts Body Composition and Skeletal Acquisition in a Gender-Specific Manner SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE Vitamin D; Parathyroid hormone; Body composition ID VITAMIN-D-RECEPTOR; D DEFICIENCY; 25-HYDROXYVITAMIN-D 1-ALPHA-HYDROXYLASE; 1,25-DIHYDROXYVITAMIN D-3; BIOMECHANICAL ANALYSES; BONE; MICE; HOMEOSTASIS; PHENOTYPE; HORMONE AB The vitamin D receptor (VDR) is crucial for virtually all of vitamin D's actions and is thought to be ubiquitously expressed. We hypothesized that disruption of one allele of the VDR gene would impact bone development and would have metabolic consequences. Body composition and bone mass (BMD) in VDR heterozygous (VDR HET) mice were compared to those obtained in male and female VDR KO and WT mice at 8 weeks of age. Male mice were also evaluated at 16 weeks, and bone marrow mesenchymal stem cell (MSC) differentiation was evaluated in VDR female mice. Additionally, female VDR HET and WT mice received intermittent PTH treatment or vehicle (VH) for 4 weeks. BMD was determined at baseline and after treatment. MRI was done in vivo at the end of treatment; mu CT and bone histomorphometry were performed after killing the animals. VDR HET male mice had normal skeletal development until 16 weeks of age but showed significantly less gain in fat mass than WT mice. In contrast, female VDR HET mice showed decreased total-body BMD at age 8 weeks but had a normal skeletal response to PTH. MSC differentiation was also impaired in VDR HET female mice. Thus, female VDR HET mice show early impairment in bone acquisition, while male VDR HET mice exhibit a lean phenotype. Our results indicate that the VDR HET mouse is a useful model for studying the metabolic and skeletal impact of decreased vitamin D sensitivity. C1 [de Paula, Francisco J. A.; Dick-de-Paula, Ingrid; Bornstein, Sheila; Rostama, Bahman; Le, Phuong; Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME 04074 USA. [de Paula, Francisco J. A.; Dick-de-Paula, Ingrid] USP, Dept Internal Med, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP, Brazil. [Lotinun, Sutada] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Baron, Roland] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Baron, Roland] Massachusetts Gen Hosp, Sch Dent Med & Endocrine Unit, Boston, MA 02114 USA. RP Rosen, CJ (reprint author), Maine Med Ctr, Res Inst, Res Dr 81, Scarborough, ME 04074 USA. EM rosenc@mmc.org; idickp@gmail.com; bornss@mmc.org; bahman.rostama@maine.edu; lep@mmc.org; Sutada_Lotinun@hsdm.harvard.edu; roland_baron@hms.harvard.edu; rosenc@mmc.org RI de Paula, Francisco/D-5026-2012; OI de Paula, Francisco/0000-0003-1262-3486; Lotinun, Sutada/0000-0002-5127-3039 FU National Council for Scientific and Technological Development (CNPq), Brazil [201650/2008-8]; CAPES, Brazil [0102-09-1] FX We thank Terry M. Handerson and Marilena Preda for technical assistance in mu CT and MRI exams, respectively. F. J. A. P. received financial support from the National Council for Scientific and Technological Development (CNPq), Brazil (201650/2008-8). I. D.-P. received financial support from CAPES, Brazil (0102-09-1). NR 35 TC 17 Z9 17 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD SEP PY 2011 VL 89 IS 3 BP 179 EP 191 DI 10.1007/s00223-011-9505-1 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 808KH UT WOS:000293976100001 PM 21637996 ER PT J AU Hartley, CA Fischl, B Phelps, EA AF Hartley, Catherine A. Fischl, Bruce Phelps, Elizabeth A. TI Brain Structure Correlates of Individual Differences in the Acquisition and Inhibition of Conditioned Fear SO CEREBRAL CORTEX LA English DT Article DE cortical thickness; emotion regulation; fear conditioning; individual differences; insula ID MEDIAL PREFRONTAL CORTEX; HUMAN CEREBRAL-CORTEX; SURFACE-BASED ANALYSIS; AMYGDALA VOLUME; INSULAR CORTEX; EXTINCTION; ACTIVATION; EMOTION; PAIN; ANTICIPATION AB Research employing aversive conditioning paradigms has elucidated the neurocircuitry involved in acquiring and diminishing fear responses. However, the factors underlying individual differences in fear acquisition and inhibition are not presently well understood. In this study, we explored whether the magnitude of individuals' acquired fear responses and the modulation of these responses via 2 fear reduction methods were correlated with structural differences in brain regions involved in affective processing. Physiological and structural magnetic resonance imaging data were obtained from experiments exploring extinction retention and intentional cognitive regulation. Our results identified 2 regions in which individual variation in brain structure correlated with subjects' fear-related arousal. Confirming previous results, increased thickness in ventromedial prefrontal cortex was correlated with the degree of extinction retention. Additionally, subjects with greater thickness in the posterior insula exhibited larger conditioned responses during acquisition. The data suggest a trend toward a negative correlation between amygdala volume and fear acquisition magnitude. There was no significant correlation between fear reduction via cognitive regulation and thickness in our prefrontal regions of interest. Acquisition and regulation measures were uncorrelated, suggesting that while certain individuals may have a propensity toward increased expression of conditioned fear, these responses can be diminished via both extinction and cognitive regulation. C1 [Hartley, Catherine A.; Phelps, Elizabeth A.] NYU, Dept Psychol, New York, NY 10003 USA. [Fischl, Bruce] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Boston, MA 02114 USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Phelps, Elizabeth A.] NYU, Ctr Neural Sci, New York, NY 10003 USA. RP Phelps, EA (reprint author), NYU, Dept Psychol, 6 Washington Pl,Meyer Hall, New York, NY 10003 USA. EM liz.phelps@nyu.edu FU National Institute of Mental Health [MH072279]; National Science Foundation; National Center for Research Resources [P41-RR14075, R01 RR16594-01A1]; National Center for Research Resources Biomedical Informatics Research Network [BIRN002, U24 RR021382]; National Institute on Aging [AG02238]; National Institute for Biomedical Imaging and Bioengineering [R01EB001550, R01EB006758]; National Institute for Neurological Disorders and Stroke [R01NS052585-01]; Mental Illness and Neuroscience Discovery Institute; National Institutes of Health through the NIH Roadmap for Medical Research [U54 EB005149]; Ellison Medical Foundation FX This work was supported by National Institute of Mental Health grants to E. A. P (MH072279) and by a National Science Foundation Graduate Research Fellowship to C. A. H. Support for this research was provided to B. F. in part by the National Center for Research Resources (P41-RR14075, R01 RR16594-01A1); National Center for Research Resources Biomedical Informatics Research Network Morphometric Project (BIRN002, U24 RR021382); National Institute on Aging (AG02238); National Institute for Biomedical Imaging and Bioengineering (R01EB001550, R01EB006758); National Institute for Neurological Disorders and Stroke (R01NS052585-01); Mental Illness and Neuroscience Discovery Institute and is part of the National Alliance for Medical Image Computing (NAMIC), funded by the National Institutes of Health through the NIH Roadmap for Medical Research (U54 EB005149). Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation. NR 79 TC 50 Z9 51 U1 5 U2 22 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2011 VL 21 IS 9 BP 1954 EP 1962 DI 10.1093/cercor/bhq253 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 807PH UT WOS:000293911700002 PM 21263037 ER PT J AU Zukotynski, KA Israel, DA Kim, CK AF Zukotynski, Katherine A. Israel, David A. Kim, Chun K. TI FDG Uptake in Lipomatous Hypertrophy of the Interatrial Septum Is Not Likely Related to Brown Adipose Tissue SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE lipomatous hypertrophy; brown adipose tissue; FDG; PET ID MASSIVE FATTY DEPOSITS; MORPHOLOGIC FEATURES; PET/CT AB Lipomatous hypertrophy of the interatrial septum (LHIS) may be associated with arrhythmias or sudden death. Increased fluorine-18 fluorodeoxyglucose (FDG) uptake in LHIS is occasionally found on positron emission tomography, and has been attributed to metabolically active brown adipose tissue (BAT) contained within LHIS. We report a case of a patient suggesting that neither of the 2 currently known mechanisms of glucose uptake by BAT is responsible for FDG uptake in LHIS, unless a mechanism of BAT activation exists that has not been previously described. This study also suggests that FDG uptake is unlikely to be due to cardiomyocytes contained within LHIS. Inflammation is a potential mechanism, although further investigation is needed. C1 [Kim, Chun K.] Harvard Univ, Brigham & Womens Hosp, Div Nucl Med & Mol Imaging, Dept Radiol,Med Sch, Boston, MA 02115 USA. [Zukotynski, Katherine A.; Israel, David A.] Harvard Univ, Dana Farber Canc Inst, Dept Imaging, Sch Med, Boston, MA 02115 USA. RP Kim, CK (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Nucl Med & Mol Imaging, Dept Radiol,Med Sch, 75 Francis St,ASB1 L1-037, Boston, MA 02115 USA. EM ckkim@bwh.harvard.edu NR 17 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD SEP PY 2011 VL 36 IS 9 BP 767 EP 769 DI 10.1097/RLU.0b013e318219b353 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 804WS UT WOS:000293685600010 PM 21825845 ER PT J AU Locke, C McEuen, J Felder, RS Lesselroth, B Barrett, TW Stevens, B Pope, DS AF Locke, Christy McEuen, Judy Felder, Robert S. Lesselroth, Blake Barrett, Thomas W. Stevens, Brent Pope, Diana S. TI Evaluating an Insulin Infusion Protocol in an Acute Care Setting SO CLINICAL NURSE SPECIALIST LA English DT Article DE hospitalization; hyperglycemia; nursing protocols ID ASSOCIATION CONSENSUS STATEMENT; GLYCEMIC CONTROL AB Objective: The objective of the present study was to evaluate the adherence, safety, and effectiveness of a paper versus an electronic insulin infusion protocol. Design: This quasi-experimental implementation study compared experimental and control groups using a nonrandomized prospective cohort design. Setting: The study was performed at 2 surgical units within a federal tertiary care teaching hospital. Sample: Fifty-eight registered nurses volunteered. Methods: We compared time intervals using electronic time stamps from glucometers and insulin infusion devices to measure protocol adherence. We assessed perceived adherence using a nurse survey, and, to evaluate safety, we reviewed each paper protocol infusion calculation for correctness. Findings: Median times from blood glucose acquisition to infusion rate adjustment did not differ significantly between groups (P = .215). The majority of infusions (96.6%) had glucose acquisition times within the acceptable range. Median values of time to next "glucose due" did not differ significantly (P = .88), and relative variation in median glucose reporting times did not differ significantly between groups (P = .16). Evaluation of 877 paper protocol entries demonstrated a 10.7% (n = 94) calculation error rate. Registered nurses within the electronic group reported greater ease in balancing workload when compared with paper protocol use (P = .03). Attitudes did not differ significantly between groups in areas of determining infusion adjustment, bolus insulin dose, next glucose due, ease of access, understanding protocol, or overall satisfaction. Conclusions: This study demonstrates that one can adhere to an insulin infusion protocol, regardless of the format (paper or electronic), in the medical-surgical setting. Our results suggest there are safety and nurse workload benefits when an electronic protocol was used. Implications: Adherence, safety, and effectiveness can be achieved when using insulin infusion in the medical-surgical setting. C1 [Locke, Christy; McEuen, Judy; Lesselroth, Blake; Barrett, Thomas W.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Locke, Christy; Felder, Robert S.; Stevens, Brent; Pope, Diana S.] Portland VA Med Ctr, Portland, OR USA. RP Locke, C (reprint author), 22117 NE 267th Ct, Battle Ground, WA 98604 USA. EM christine.locke@va.gov FU Quality Enhancement Research Initiative (QUERI), Office of Research and Development, Veterans Health Administration FX This study was funded through the Quality Enhancement Research Initiative (QUERI), Office of Research and Development, Veterans Health Administration ($27 000). NR 16 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD SEP-OCT PY 2011 VL 25 IS 5 BP 237 EP 243 DI 10.1097/NUR.0b013e3182299522 PG 7 WC Nursing SC Nursing GA 808DT UT WOS:000293957500007 PM 22649844 ER PT J AU Bachoura, A Guitton, TG Smith, RM Vrahas, MS Zurakowski, D Ring, D AF Bachoura, Abdo Guitton, Thierry G. Smith, R. Malcolm Vrahas, Mark S. Zurakowski, David Ring, David TI Infirmity and Injury Complexity are Risk Factors for Surgical-site Infection after Operative Fracture Care SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL KNEE-REPLACEMENT; NOSOCOMIAL INFECTIONS; ORTHOPEDIC PATIENTS; WOUND-INFECTION; JOINT INFECTION; DEEP INFECTION; ARTHROPLASTY; PREVENTION; SURGERY; HIP AB Background Orthopaedic surgical-site infections prolong hospital stays, double rehospitalization rates, and increase healthcare costs. Additionally, patients with orthopaedic surgical-site infections (SSI) have substantially greater physical limitations and reductions in their health-related quality of life. However, the risk factors for SSI after operative fracture care are unclear. Questions/purpose We determined the incidence and quantified modifiable and nonmodifiable risk factors for SSIs in patients with orthopaedic trauma undergoing surgery. Patients and Methods We retrospectively indentified, from our prospective trauma database and billing records, 1611 patients who underwent 1783 trauma-related procedures between 2006 and 2008. Medical records were reviewed and demographics, surgery-specific data, and whether the patients had an SSI were recorded. We determined which if any variables predicted SSI. Results Six factors independently predicted SSI: (1) the use of a drain, OR 2.3, 95% CI (1.3-3.8); (2) number of operations OR 3.4, 95% CI (2.0-6.0); (3) diabetes, OR 2.1, 95% CI (1.2-3.8); (4) congestive heart failure (CHF), OR 2.8, 95% CI (1.3-6.5); (5) site of injury tibial shaft/plateau, OR 2.3, 95% CI (1.3-4.2); and (6) site of injury, elbow, OR 2.2, 95% CI (1.1-4.7). Conclusion The risk factors for SSIs after skeletal trauma are most strongly determined by nonmodifiable factors: patient infirmity (diabetes and heart failure) and injury complexity (site of injury, number of operations, use of a drain). Level of Evidence Level II, prognostic study. See the Guideline for Authors for a complete description of levels of evidence. C1 [Ring, David] Massachusetts Gen Hosp, Yawkey Ctr, Boston, MA 02114 USA. [Bachoura, Abdo; Guitton, Thierry G.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. [Smith, R. Malcolm; Vrahas, Mark S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA USA. [Zurakowski, David] Harvard Univ, Sch Med, Dept Anesthesia, Childrens Hosp Boston, Boston, MA 02115 USA. [Zurakowski, David] Harvard Univ, Sch Med, Dept Surg, Childrens Hosp Boston, Boston, MA 02115 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Guitton, Thierry/0000-0002-2599-1985 NR 47 TC 26 Z9 28 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 2011 VL 469 IS 9 BP 2621 EP 2630 DI 10.1007/s11999-010-1737-2 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 800YX UT WOS:000293404700031 PM 21161736 ER PT J AU Ahmadi, N Mao, SS Hajsadeghi, F Hacioglu, Y Flores, F Gao, YL Ebrahimi, R Budoff, M AF Ahmadi, Naser Mao, Song S. Hajsadeghi, Fereshteh Hacioglu, Yalcin Flores, Ferdinand Gao, Yanlin Ebrahimi, Ramin Budoff, Matthew TI Relation of subclinical left and right ventricular dysfunctions measured by computed tomography angiography with the severity of coronary artery disease SO CORONARY ARTERY DISEASE LA English DT Article DE computed tomography angiography; coronary artery calcium; coronary artery disease; subclinical right and left ventricular dysfunction ID CONGESTIVE-HEART-FAILURE; MYOCARDIAL BLOOD-FLOW; MAGNETIC-RESONANCE; SYSTOLIC FUNCTION; ELECTRON-BEAM; PROGNOSTIC IMPLICATIONS; CARDIOVASCULAR-DISEASE; INOTROPIC RESERVE; INFARCTION; MORTALITY AB Objective Ventricular dysfunction in asymptomatic patients is directly linked to the eventual development of symptomatic congestive heart failure. This study investigates whether subclinical left ventricular (LV) and right ventricular (RV) dysfunctions measured by computed tomography angiography is associated with the severity of coronary artery disease (CAD). Methods and results We studied 1608 consecutive patients with suspected CAD (age 62 +/- 10 years, 64% male), who underwent coronary artery calcium (CAC) scanning and computed tomography angiography. RV and LV volumes at end systole and end diastole were measured, and stroke volume and ejection fraction were calculated using the Simpson method and piecewise smooth subdivision surface (PSSS) method. Analysis by Simpson was performed on short axis and apical four-chamber views. Axial images were used to measure RV and LV volumes by the PSSS method. CAD was defined as normal, nonobstructive, and obstructive (0% stenosis, luminal stenosis 1-49 and 50%+, respectively). There was a strong agreement between PSSS and Simpson method RV ejection fraction (RVEF) and LV ejection fraction (LVEF) measurement. RVEF and LVEF decreased proportionally from CAC 0 to CAC 100+, also from normal-to-diseased coronaries (P=0.001). After adjustment for cardiovascular risk factors, the mean LVEF and RVEF decreased 2.8 and 2.4%, respectively in CAC 100+ compared with CAC 0. Similarly, LVEF and RVEF decreased significantly in nonobstructive CAD (-3.5 and -3.1%, respectively) and obstructive CAD (-5.9 and -4.5%, respectively) compared with normal coronaries, respectively (P<0.05). The relative risk of each 5% decrease in LVEF and RVEF was 1.33 and 1.29 for nonobstructive CAD and 1.54 and 1.33 for obstructive CAD, respectively. Conclusion The presence and severity of coronary atherosclerosis is significantly associated with subclinical RV and LV dysfunctions. Coron Artery Dis 22: 380-387 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Ahmadi, Naser; Mao, Song S.; Hajsadeghi, Fereshteh; Hacioglu, Yalcin; Flores, Ferdinand; Gao, Yanlin; Budoff, Matthew] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Ebrahimi, Ramin] Univ Calif Los Angeles, Los Angeles, CA USA. [Ebrahimi, Ramin] Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Ahmadi, N (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, 1124 W Carson St,RB2, Torrance, CA 90502 USA. EM nahmadi@labiomed.org NR 37 TC 1 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0954-6928 EI 1473-5830 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD SEP PY 2011 VL 22 IS 6 BP 380 EP 387 DI 10.1097/MCA.0b013e328347506f PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 802HC UT WOS:000293498900002 PM 21666441 ER PT J AU Britos, M Smoot, E Liu, KD Thompson, BT Checkley, W Brower, RG AF Britos, Martin Smoot, Elizabeth Liu, Kathleen D. Thompson, B. Taylor Checkley, William Brower, Roy G. CA Natl Inst Hlth Acute Resp Distress TI The value of positive end-expiratory pressure and FIO2 criteria in the definition of the acute respiratory distress syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; clinical trials; mechanical; positive end-expiratory pressure; randomized; ventilation ID ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; MECHANICAL VENTILATION; PROTECTIVE VENTILATION; CLINICAL-TRIAL; TIDAL VOLUMES; RECRUITMENT; PULMONARY; SURVIVAL; OUTCOMES AB Objectives: The criteria that define acute lung injury and the acute respiratory distress syndrome include PaO2/FIO2 but not positive end-expiratory pressure or FIO2. PaO2/FIO2 ratios of some patients increase substantially after mechanical ventilation with positive end-expiratory pressure of 5-10 cm H2O, and the mortality of these patients may be lower than those whose PaO2/FIO2 ratios remain <200. Also, PaO2/FIO2 may increase when FIO2 is raised from moderate to high levels, suggesting that patients with similar PaO2/FIO2 ratios but different FIO2 levels have different risks of mortality. The primary purpose of this study was to assess the value of adding baseline positive end-expiratory pressure and FIO2 to PaO2/FIO2 for predicting mortality of acute lung injury/acute respiratory distress syndrome patients enrolled in Acute Respiratory Distress Syndrome Network clinical trials. We also assessed effects of two study interventions on clinical outcomes in subsets of patients with mild and severe hypoxemia as defined by PaO2/FIO2. Design: Analysis of baseline physiologic data and outcomes of patients previously enrolled in clinical trials conducted by the National Institutes of Health Acute Respiratory Distress Syndrome Network. Setting: Intensive care units of 40 hospitals in North America. Patients: Two thousand three hundred and twelve patients with acute lung injury/acute respiratory distress syndrome. Interventions: None. Measurements and Main Results: Only 1.3% of patients enrolled in Acute Respiratory Distress Syndrome Network trials had baseline positive end-expiratory pressure <5 cm H2O, and 50% had baseline positive end-expiratory pressure >= 10 cm H2O. Baseline PaO2/FIO2 predicted mortality, but after controlling for PaO2/FIO2, baseline positive end-expiratory pressure did not predict mortality. In contrast, after controlling for baseline PaO2/FIO2, baseline FIO2 did predict mortality. Effects of two study interventions (lower tidal volumes and fluid-conservative hemodynamic management) were similar in mild and severe hypoxemia subsets as defined by PaO2/FIO2 ratios. Conclusion: At Acute Respiratory Distress Syndrome Network hospitals, the addition of baseline positive end-expiratory pressure would not have increased the value of PaO2/FIO2 for predicting mortality of acute lung injury/acute respiratory distress syndrome patients. In contrast, the addition of baseline FIO2 to PaO2/FIO2 could be used to identify subsets of patients with low or high mortality. (Crit Care Med 2011; 39: 2025-2030) C1 [Brower, Roy G.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Britos, Martin] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Smoot, Elizabeth] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Liu, Kathleen D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Brower, RG (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. EM rbrower@jhmi.edu FU NHLBI [N01-HR-46054-46064, N01-HR-56165-56179] FX Supported, in part, by NHLBI Contracts N01-HR-46054-46064 and N01-HR-56165-56179. NR 29 TC 34 Z9 37 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2011 VL 39 IS 9 BP 2025 EP 2030 DI 10.1097/CCM.0b013e31821cb774 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 808TH UT WOS:000294000800002 PM 21532473 ER PT J AU Shander, A Fleisher, LA Barie, PS Bigatello, LM Sladen, RN Watson, CB AF Shander, Aryeh Fleisher, Lee A. Barie, Philip S. Bigatello, Luca M. Sladen, Robert N. Watson, Charles B. TI Clinical and economic burden of postoperative pulmonary complications: Patient safety summit on definition, risk-reducing interventions, and preventive strategies SO CRITICAL CARE MEDICINE LA English DT Review DE biofilm; endotracheal tube; microaspiration; postoperative pneumonia; postoperative pulmonary complications; ventilator-associated pneumonia ID VENTILATOR-ASSOCIATED PNEUMONIA; SUBGLOTTIC SECRETION DRAINAGE; HOSPITAL-ACQUIRED PNEUMONIA; QUALITY IMPROVEMENT PROGRAM; RANDOMIZED CONTROLLED-TRIAL; COATED ENDOTRACHEAL-TUBES; COLLEGE-OF-PHYSICIANS; INTENSIVE-CARE-UNIT; PROLONGED MECHANICAL VENTILATION; ACUTE RESPIRATORY-FAILURE AB Objective: Postoperative pulmonary complications are a major contributor to the overall risk of surgery. We convened a patient safety summit to discuss ways to enhance physician awareness of postoperative pulmonary complications, advance postoperative pulmonary complications as a substantive public health concern demanding national attention, recommend strategies to reduce the deleterious impact of postoperative pulmonary complications on clinical outcomes and healthcare costs, and establish an algorithm that will help identify patients who are at increased risk for postoperative pulmonary complications. Data Sources: We conducted PubMed searches for relevant literature on postoperative pulmonary complications in addition to using the summit participants' experience in the management of patients with postoperative pulmonary complications. Data Synthesis: Postoperative pulmonary complications are common, are associated with increased morbidity and mortality, and adversely affect financial outcomes in health care. A multifaceted approach is necessary to reduce the incidence of postoperative pulmonary complications. Identifying a measurable marker of risk will facilitate the targeted implementation of risk-reduction strategies. Conclusions: The most practicable marker that identifies patients at highest risk for postoperative pulmonary complications is the need for postoperative mechanical ventilation of a cumulative duration >48 hrs. (Crit Care Med 2011; 39: 2163-2172) C1 [Shander, Aryeh] Englewood Hosp & Med Ctr, Englewood, NJ USA. [Fleisher, Lee A.] Univ Penn, Philadelphia, PA 19104 USA. [Barie, Philip S.] Weill Cornell Med Coll, New York, NY USA. [Bigatello, Luca M.] VA Boston Healthcare Syst, W Roxbury, MA USA. [Sladen, Robert N.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Watson, Charles B.] Yale New Haven Hlth Syst, Bridgeport, CT USA. RP Shander, A (reprint author), Englewood Hosp & Med Ctr, Englewood, NJ USA. EM aryeh.shander@ehmc.com FU Covidien FX Dr. Shander consulted for and received honoraria/speaking fees from Covidien. Dr. Bigatelllo consulted for Covidien. The remaining authors have not disclosed any potential conflicts of interest. NR 130 TC 41 Z9 44 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2011 VL 39 IS 9 BP 2163 EP 2172 DI 10.1097/CCM.0b013e31821f0522 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 808TH UT WOS:000294000800018 PM 21572323 ER PT J AU Marcum, ZA Fried, LF AF Marcum, Zachary A. Fried, Linda F. TI Aging and antihypertensive medication-related complications in the chronic kidney disease patient SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE adverse drug events; aging; antihypertensives; chronic kidney disease; older adults ID ISOLATED SYSTOLIC HYPERTENSION; CONVERTING-ENZYME-INHIBITORS; HIGH BLOOD-PRESSURE; ELDERLY-PATIENTS; HYPERKALEMIA RISK; RANDOMIZED-TRIAL; DOUBLE-BLIND; OLDER; HYPOTENSION; MORTALITY AB Purpose of review We have reviewed the recent literature to describe the potential medication errors and adverse drug events (ADEs) associated with antihypertensives among older adults with chronic kidney disease (CKD). Recent findings Overall, few studies have been published describing ADEs in older adults with CKD. Several examined hyperkalemia associated with angiotensin-converting enzyme (ACE)-inhibitor/angiotensin II receptor blocker (ARB), diuretic (potassium-sparing), and beta-blocker use. Additional studies described acute kidney injury (AKI) most commonly with ACE-inhibitor/ARB therapy. Finally, orthostatic hypotension was evaluated in those taking ACE-inhibitor/ARB, b-blocker, or calcium-channel blocker therapy. In the absence of robust literature examining these events in this understudied population, one must consider age-related antihypertensive pharmacokinetic/pharmacodynamic profiles concomitantly with the patient's comorbidities and other medications in order to minimize the risk for potential medication errors, drug-drug interactions, and ADEs. Summary Some of the most common ADEs associated with antihypertensive use in older adults with CKD include hyperkalemia, AKI, and orthostatic hypotension. Diligent monitoring of laboratory data, vital signs, and potential drug-drug interactions may mitigate serious ADEs caused by antihypertensives in this high-risk patient population. C1 [Marcum, Zachary A.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Fried, Linda F.] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. [Fried, Linda F.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. RP Marcum, ZA (reprint author), Univ Pittsburgh, Sch Med, Dept Med Geriatr Med, Kaufmann Med Bldg,Suite 500,3471 5th Ave, Pittsburgh, PA 15213 USA. EM zam12@pitt.edu FU National Institute on Aging [T32 AG021885] FX This review was supported by funding from the National Institute on Aging (T32 AG021885). NR 38 TC 12 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 2011 VL 20 IS 5 BP 449 EP 456 DI 10.1097/MNH.0b013e32834902ad PG 8 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 806CC UT WOS:000293779100001 PM 21670671 ER PT J AU Markowitz, JT Laffel, LMB Volkening, LK Anderson, BJ Nansel, TR Weissberg-Benchell, J Wysocki, T AF Markowitz, J. T. Laffel, L. M. B. Volkening, L. K. Anderson, B. J. Nansel, T. R. Weissberg-Benchell, J. Wysocki, T. TI Validation of an abbreviated adherence measure for young people with Type 1 diabetes SO DIABETIC MEDICINE LA English DT Article DE adherence; paediatrics; Type 1 diabetes ID STRUCTURED INTERVIEW; SELF-MANAGEMENT; INTERVENTION; RELIABILITY; VALIDITY; SCALE AB Aims Adherence to diabetes-related tasks is an important construct. The Diabetes Self-Management Profile is a validated, semi-structured interview assessing adherence in paediatric patients with Type 1 diabetes. We created and validated a brief questionnaire version of the Diabetes Self-Management Profile called the Diabetes Self-Management Questionnaire. Methods Young people with Type 1 diabetes, ages 9-15 years (n = 338) and their parents provided data from chart review, interview and questionnaires. Results Diabetes Self-Management Questionnaire scores correlated significantly with Diabetes Self-Management Profile scores, HbA(1c), blood glucose monitoring frequency and other measures associated with adherence and/or glycaemic control (P <= 0.01 for all). Young people and parent scores were correlated (r = 0.55, P < 0.0001). The Diabetes Self-Management Questionnaire demonstrated modest internal consistency (Cronbach's alpha = 0.59), adequate for a brief measure of multidimensional adherence. In addition, factor analysis confirmed one factor. Conclusions This brief adherence questionnaire demonstrated construct validity in young people 9-15 years old and their parents and may have utility in clinical and research settings. C1 [Laffel, L. M. B.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Anderson, B. J.] Baylor Coll Med, Houston, TX 77030 USA. [Nansel, T. R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Weissberg-Benchell, J.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Wysocki, T.] Nemours Childrens Clin, Jacksonville, FL USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu OI Nansel, Tonja/0000-0002-8298-7595 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); NIH [T32 DK007260]; National Institute of Diabetes and Digestive and Kidney Diseases [DK-46887]; Charles H. Hood Foundation; Maria Griffin Drury Pediatric Fund; Katherine Adler Astrove Youth Education Fund; [N01-HD-4-3363]; [N01-HD-4-3362]; [N01-HD-4-3361]; [N01-HD-4-3364]; [N01-HD-3-3360] FX This research was supported in part by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The following investigators and institutions made up the steering committee of the Family Management of Childhood Diabetes multi-site trial: Jill Weissberg-Benchell PhD, Grayson Holmbeck PhD (Children's Memorial Hospital, Chicago, Contract N01-HD-4-3363); Barbara Anderson PhD (Texas Children's Hospital, Houston, Contract N01-HD-4-3362); Tim Wysocki PhD, Amanda Lochrie PhD (Nemours Children's Clinic, Jacksonville, FL, Contract N01-HD-4-3361); Lori Laffel MD MPH, Deborah Butler MSW, Lisa Volkening MA (Joslin Diabetes Center, Boston, Contract N01-HD-4-3364); Tonja Nansel PhD, Ronald Iannotti PhD (NICHD, Bethesda, MD); Cheryl McDonnell PhD, MaryAnn D'Elio (James Bell Associates, Arlington, VA, Contract N01-HD-3-3360). This work was also supported in part by NIH Training Grant No. T32 DK007260, a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-46887), the Charles H. Hood Foundation, the Maria Griffin Drury Pediatric Fund and the Katherine Adler Astrove Youth Education Fund. NR 12 TC 10 Z9 10 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD SEP PY 2011 VL 28 IS 9 BP 1113 EP 1117 DI 10.1111/j.1464-5491.2011.03321.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 807NG UT WOS:000293905000018 PM 21843307 ER PT J AU Tansey, M Laffel, L Cheng, J Beck, R Coffey, J Huang, E Kollman, C Lawrence, J Lee, J Ruedy, K Tamborlane, W Wysocki, T Xing, D AF Tansey, M. Laffel, L. Cheng, J. Beck, R. Coffey, J. Huang, E. Kollman, C. Lawrence, J. Lee, J. Ruedy, K. Tamborlane, W. Wysocki, T. Xing, D. CA Juvenile Diabet Res Fdn Continuous TI Satisfaction with continuous glucose monitoring in adults and youths with Type 1 diabetes SO DIABETIC MEDICINE LA English DT Article DE adherence; continuous glucose monitors; Type 1 diabetes ID MANAGEMENT AB Aims To describe satisfaction with continuous glucose monitoring in Type 1 diabetes; to correlate continuous glucose monitoring satisfaction scores with usage; and to identify common themes in perceived benefits and barriers of monitoring reported by adults, youths and the parents of youths in the Juvenile Diabetes Research Foundation continuous glucose monitoring trials. Methods The Continuous Glucose Monitoring Satisfaction Scale questionnaire was completed after 6 months of monitoring. Participants also answered open-ended queries of positive and negative attributes of continuous glucose monitoring. Results More frequent monitoring was associated with higher satisfaction for adults (n = 224), youths (n = 208) and parents of youths (n = 192) (all P < 0.001) in both the 'benefits' and 'hassles' sub-scales of the Continuous Glucose Monitoring Satisfaction Scale, but the greatest differences between the two groups involved scores on hassle items. Common barriers to monitoring use included insertion pain, system alarms and body issues; while common benefits included glucose trend data, opportunities to self-correct out-of-range glucose levels and to detect hypoglycaemia. Conclusions As frequent use of continuous glucose monitoring is associated with improved glycaemic control without increased hypoglycaemia it is important to overcome barriers, reinforce benefits and set realistic expectations for this technology in order to promote its more consistent and frequent use in individuals with Type 1 diabetes. C1 [Tansey, M.; Coffey, J.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Laffel, L.] Joslin Diabet Ctr, Boston, MA USA. [Huang, E.] Univ Chicago, Chicago, IL 60637 USA. [Lawrence, J.] Kaiser Permanente So Calif, Dept Res & Epidemiol, Gardena, CA 90249 USA. [Lee, J.] Univ Michigan, Child Hlth Evaluat & Res Unit, Ann Arbor, MI 48109 USA. [Tamborlane, W.] Yale Univ, Sch Med, New Haven, CT 06520 USA. RP Tansey, M (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM jdrfapp@jaeb.org FU Juvenile Diabetes Research Foundation Inc. [22-2006-1107, 22-2006-1117, 22-2006-1112, 22-2006-1123, 01-2006-8031]; Abbott Diabetes Care Inc.; Medtronic MiniMed Inc; Medtronic MiniMed Inc. FX Study funding was provided by the Juvenile Diabetes Research Foundation Inc. (grant numbers 22-2006-1107, 22-2006-1117, 22-2006-1112, 22-2006-1123 and 01-2006-8031). Continuous glucose monitors and sensors were purchased at a bulk discount price from DexCom Inc. (San Diego, CA), Medtronic MiniMed Inc. (Northridge, CA) and Abbott Diabetes Care Inc. (Alameda, CA). Home glucose meters and test strips were provided to the study by LifeScan Inc. and Abbott Diabetes Care Inc. The companies had no involvement in the design, conduct or analysis of the trial or the manuscript preparation. Below is a listing of relationships of the investigators with companies that make products relevant to the manuscript. Research funds where listed below were provided to the legal entity that employs the individual and not directly to the individual. Mrs Coffee received consulting fees from Abbott Diabetes Care Inc.; Dr Kollman reports having received consulting fees from Medtronic MiniMed Inc; Dr Laffel reports having received a speaker honorarium from Lifescan Inc., consulting fees and a speaker honorarium from Abbott Diabetes Care Inc. and consulting fees and research funding from Medtronic MiniMed Inc.; Dr Tamborlane reports having received consulting fees from Medtronic MiniMed Inc. NR 8 TC 36 Z9 36 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD SEP PY 2011 VL 28 IS 9 BP 1118 EP 1122 DI 10.1111/j.1464-5491.2011.03368.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 807NG UT WOS:000293905000019 PM 21692844 ER PT J AU Mosquera, JM Dal Cin, P Mertz, KD Perner, S Davis, IJ Fisher, DE Rubin, MA Hirsch, MS AF Mosquera, Juan-Miguel Dal Cin, Paola Mertz, Kirsten D. Perner, Sven Davis, Ian J. Fisher, David E. Rubin, Mark A. Hirsch, Michelle S. TI Validation of a TFE3 Break-apart FISH Assay for Xp11.2 Translocation Renal Cell Carcinomas SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE renal cell carcinoma; Xp11.2; translocation; TFE3; fluorescence in-situ hybridization (FISH); immunohistochemistry ID OF-THE-LITERATURE; TRANSCRIPTION FACTOR GENE; SOFT PART SARCOMA; PROSTATE-CANCER; YOUNG-ADULTS; FUSION; CHILDREN; NEOPLASMS; CYTOGENETICS; TUMOR AB Renal cell carcinomas (RCCs) with an Xp11.2 translocation predominantly affect young patients, and can present at an advanced stage. However, more cases in older patients and incidentally detected cancers at earlier stages are also being identified. As the histology of Xp11.2 RCCs overlaps with clear cell and papillary RCCs, it is not infrequent that Xp11.2 RCCs are overlooked and misdiagnosed. The objective of this study was to validate the use of fluorescence in-situ hybridization (FISH) for identifying Xp11.2 RCCs. One hundred fifty-eight consecutive, unselected renal tumors were evaluated in tissue microarrays, including 109 clear cell RCCs, 20 papillary RCCs, 3 RCCs with mixed papillary and clear cell features, 1 Xp11.2 translocation RCC, 8 chromophobe RCCs, 10 oncocytomas, and 7 angiomyolipomas. FISH evaluation was performed blinded to karyotype data, available in about two-thirds of cases. Furthermore, conventional sections of 4 Xp11.2 RCCs, 4 RCCs with mixed papillary and clear cell features, and 4 cases of alveolar soft part sarcoma (the latter for control purposes) were also assessed by FISH. Break-apart signals were homogeneously identified throughout tumor cells in 2 cases from the tissue microarrays including 1 known Xp11.2 RCC and 1 misdiagnosed Xp11.2 RCC. All conventional sections from the Xp11.2 RCC and alveolar soft part sarcoma cases were positive for the TFE3 rearrangement by FISH. All remaining cases were negative. Our study shows the clinical application of FISH in formalin-fixed, paraffin-embedded tissue for detection of Xp11.2 translocation RCCs and other tumors with this genetic aberration. C1 [Mosquera, Juan-Miguel; Dal Cin, Paola; Mertz, Kirsten D.; Perner, Sven; Rubin, Mark A.; Hirsch, Michelle S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Mosquera, Juan-Miguel; Dal Cin, Paola; Mertz, Kirsten D.; Perner, Sven; Davis, Ian J.; Fisher, David E.; Rubin, Mark A.; Hirsch, Michelle S.] Harvard Univ, Sch Med, Boston, MA USA. [Davis, Ian J.; Fisher, David E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Davis, Ian J.; Fisher, David E.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Perner, Sven] Univ Hosp Bonn, Dept Pathol, Bonn, Germany. RP Hirsch, MS (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3, Boston, MA 02115 USA. EM mhirsch1@partners.org OI Rubin, Mark/0000-0002-8321-9950 NR 52 TC 28 Z9 29 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD SEP PY 2011 VL 20 IS 3 BP 129 EP 137 DI 10.1097/PDM.0b013e31820e9c67 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 809IL UT WOS:000294045200001 PM 21817901 ER PT J AU Janssens, ACJW Ioannidis, JPA Bedrosian, S Boffetta, P Dolan, SM Dowling, N Fortier, I Freedman, AN Grimshaw, JM Gulcher, J Gwinn, M Hlatky, MA Janes, H Kraft, P Melillo, S O'Donnell, CJ Pencina, MJ Ransohoff, D Schully, SD Seminara, D Winn, DM Wright, CF van Duijn, CM Little, J Khoury, MJ AF Janssens, A. Cecile J. W. Ioannidis, John P. A. Bedrosian, Sara Boffetta, Paolo Dolan, Siobhan M. Dowling, Nicole Fortier, Isabel Freedman, Andrew N. Grimshaw, Jeremy M. Gulcher, Jeffrey Gwinn, Marta Hlatky, Mark A. Janes, Holly Kraft, Peter Melillo, Stephanie O'Donnell, Christopher J. Pencina, Michael J. Ransohoff, David Schully, Sheri D. Seminara, Daniela Winn, Deborah M. Wright, Caroline F. van Duijn, Cornelia M. Little, Julian Khoury, Muin J. TI Strengthening the reporting of genetic risk prediction studies (GRIPS): explanation and elaboration SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GENOME-WIDE ASSOCIATION; HEART-DISEASE RISK; OPERATING CHARACTERISTIC CURVE; TYPE-2 DIABETES RISK; COMMON DISEASES; RECLASSIFICATION MEASURES; MACULAR DEGENERATION; DIAGNOSTIC-ACCURACY; CARDIOVASCULAR RISK; RANDOMIZED-TRIALS AB The rapid and continuing progress in gene discovery for complex diseases is fuelling interest in the potential application of genetic risk models for clinical and public health practice. The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality. Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction. A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by prior reporting guidelines. These recommendations aim to enhance the transparency, quality and completeness of study reporting and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct or analysis. C1 [Janssens, A. Cecile J. W.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Fdn Res & Technol, Biomed Res Inst, Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Ioannidis, John P. A.] Tufts Med Ctr, Ctr Genet Epidemiol & Modeling, Boston, MA USA. [Ioannidis, John P. A.] Tufts Med Ctr, Tufts CTSI, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Ioannidis, John P. A.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA USA. [Bedrosian, Sara; Dowling, Nicole; Gwinn, Marta; Melillo, Stephanie; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Dolan, Siobhan M.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA. [Fortier, Isabel] Publ Populat Project Genom P3G, Montreal, PQ, Canada. [Freedman, Andrew N.; Kraft, Peter; Schully, Sheri D.; Seminara, Daniela; Winn, Deborah M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Grimshaw, Jeremy M.] Ottawa Hosp, Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Grimshaw, Jeremy M.] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Gulcher, Jeffrey] DeCODE Genet, Reykjavik, Iceland. [Hlatky, Mark A.] Stanford Univ, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA. [Janes, Holly] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA. [Janes, Holly] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Sch Med, Boston, MA USA. [Pencina, Michael J.] Boston Univ, Dept Biostat, Harvard Clin Res Inst, Boston, MA 02215 USA. [Ransohoff, David] Univ N Carolina, Sch Med, Chapel Hill, NC USA. [Wright, Caroline F.] PHG Fdn, Cambridge, England. [Little, Julian] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Janssens, ACJW (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM a.janssens@erasmusmc.nl RI Ioannidis, John/G-9836-2011; Grimshaw, Jeremy/D-8726-2013; janssens, cecile/L-1075-2015; Wright, Caroline/N-5355-2015; OI Janssens, A Cecile/0000-0002-6153-4976; Wright, Caroline/0000-0003-2958-5076; Grimshaw, Jeremy/0000-0001-8015-8243 FU National Heart, Lung, and Blood Institute; National Cancer Institute, National Institutes of Health; Donald W. Reynolds Foundation; Leducq Foundation FX This study was supported by grants from the National Heart, Lung, and Blood Institute and National Cancer Institute, National Institutes of Health; the Donald W. Reynolds Foundation; and the Leducq Foundation. Additional support for DNA extraction, reagents, and data analysis was provided by Roche Diagnostics and Amgen. Genotyping of the 9p21.3 variant was performed by Celera. The funding sources had no role in the design, conduct, or reporting of this study or the decision to submit the manuscript for publication' [53]. NR 92 TC 16 Z9 17 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD SEP PY 2011 VL 41 IS 9 BP 1010 EP 1035 DI 10.1111/j.1365-2362.2011.02493.x PG 26 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 802KJ UT WOS:000293509200013 PM 21434890 ER PT J AU Scott, SM Brown, M Come, SE AF Scott, Sarah M. Brown, Myles Come, Steven E. TI Emerging data on the efficacy and safety of fulvestrant, a unique antiestrogen therapy for advanced breast cancer SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE antiestrogen; breast cancer; estrogen receptor antagonist; estrogen receptors; fulvestrant; selective estrogen receptor modulator ID HUMAN ESTROGEN-RECEPTOR; AROMATASE INHIBITOR LETROZOLE; 2 MULTICENTER TRIALS; POSTMENOPAUSAL WOMEN; ENDOCRINE THERAPY; DOUBLE-BLIND; EARLY DISCONTINUATION; PURE ANTIESTROGEN; HORMONAL-THERAPY; RANDOMIZED-TRIAL AB Introduction: Fulvestrant is an antiestrogen therapy with a unique mechanism of action. Unlike the selective estrogen receptor modulator tamoxifen, fulvestrant has no known estrogen agonist activity and is considered a pure antiestrogen. Its primary mechanism of action is thought to result from downregulation of the estrogen receptor (ER). Considerable data have demonstrated the efficacy of fulvestrant in postmenopausal women with ER-positive advanced breast cancer, both in the first-line setting and following disease progression on tamoxifen or aromatase inhibitors. Recent studies report improved benefit with alternative dosing strategies. At all administration schedules, fulvestrant has an excellent safety profile with no significant adverse effects. Areas covered: This article provides a review of the mechanism of action of fulvestrant and the preclinical and clinical data evaluating its use as a form of endocrine therapy. The reader will gain insight into the pharmacologic properties of the drug and its role in the treatment of advanced hormone receptor-positive breast cancer in postmenopausal women. Expert opinion: Based on data demonstrating the efficacy of fulvestrant, including prolonged clinical benefit in many patients, this well-tolerated antiestrogen is an important therapy for breast cancer. The optimal position of fulvestrant in the sequence of endocrine therapies for postmenopausal women and its role in combination regimens are not yet resolved. C1 [Come, Steven E.] Dana Farber Harvard Canc Ctr, Breast Med Oncol Program, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Brown, Myles] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. RP Come, SE (reprint author), Dana Farber Harvard Canc Ctr, Breast Med Oncol Program, Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Rm CC-913, Boston, MA 02215 USA. EM scome@bidmc.harvard.edu OI Brown, Myles/0000-0002-8213-1658 NR 47 TC 14 Z9 14 U1 3 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD SEP PY 2011 VL 10 IS 5 BP 819 EP 826 DI 10.1517/14740338.2011.595560 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 808VX UT WOS:000294011000013 PM 21699443 ER PT J AU Williams, SB Lay, AH Lau, CS Josephson, DY Wilson, TG Choueiri, TK Pal, SK AF Williams, Stephen B. Lay, Aaron H. Lau, Clayton S. Josephson, David Y. Wilson, Timothy G. Choueiri, Toni K. Pal, Sumanta K. TI New therapies for castrate-resistant prostate cancer SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE castrate resistant; chemotherapy; outcomes; prostate cancer; review ID MITOXANTRONE PLUS PREDNISONE; INHIBITOR ABIRATERONE ACETATE; I CLINICAL-TRIAL; ANTITUMOR-ACTIVITY; DOCETAXEL; CYP17; IMMUNOTHERAPY; ANTIANDROGEN; CHEMOTHERAPY; MECHANISMS AB Introduction: Prostate cancer is the second leading cause of cancer death in men in the USA, and most of these deaths will occur as a result of castrate-resistant prostate cancer (CRPC) that has progressed despite androgen deprivation therapy. There has been better understanding of castration resistance and molecular mechanisms of prostate cancer progression recently, leading to new treatment strategies. Areas covered: This review focuses on emerging and new therapies for castrate-resistant prostate cancer, including hormonal therapy, immunotherapy and cytotoxic agents. Expert opinion: New treatment strategies have been developed in recent years and, with improved understanding of advanced CRPC, additional targeted treatments are expected in the near future. Further cost effectiveness research of these treatments is warranted before dissemination of these promising agents. C1 [Williams, Stephen B.; Lay, Aaron H.] Harvard Univ, Brigham & Womens Hosp, Div Urol, Sch Med, Boston, MA 02115 USA. [Lau, Clayton S.; Josephson, David Y.; Wilson, Timothy G.] City Hope Comprehens Canc Ctr, Div Urol Oncol, Dept Urol, Duarte, CA 91010 USA. [Choueiri, Toni K.] Harvard Univ, Lank Ctr Genitourinary Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Pal, Sumanta K.] City Hope Comprehens Canc Ctr, Div Genitourinary Malignancies, Dept Med Oncol & Expt Therapeut, Duarte, CA 91010 USA. RP Williams, SB (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Urol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM swilliams22@partners.org FU NCI NIH HHS [K12 CA001727] NR 34 TC 2 Z9 2 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD SEP PY 2011 VL 12 IS 13 BP 2069 EP 2074 DI 10.1517/14656566.2011.590133 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 803RZ UT WOS:000293599700007 PM 21663529 ER PT J AU Vallet, S Anderson, KC AF Vallet, Sonia Anderson, Kenneth C. TI CCR1 as a target for multiple myeloma SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE CCL3; CCR1; CCR5; chemokine; myeloma; osteoblast; osteoclast; osteolytic bone disease ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; MARROW STROMAL CELLS; CHEMOKINE RECEPTOR EXPRESSION; KAPPA-B LIGAND; IN-VIVO MODEL; BONE-DISEASE; THERAPEUTIC IMPLICATIONS; PROTEIN (MIP)-1-ALPHA; RHEUMATOID-ARTHRITIS; OSTEOLYTIC LESIONS AB Introduction: By directing cell trafficking, differentiation and growth, chemokines modulate the immune response and are involved in the pathogenesis of autoimmune diseases and cancers, including multiple myeloma (MM). MM, the second most common hematological malignancy in the US, is characterized by disordered plasma cell growth within the bone marrow microenvironment. CCL3 and its receptors, CCR1 in particular, play a central role in the pathogenesis of MM and MM-induced osteolytic bone disease. Areas covered: This review describes the functional role of CCR1 in MM and the preclinical results observed with CCR1 antagonists. CCL3 and CCR1 stimulate tumor growth, both directly and indirectly, via upregulation of cell adhesion and cytokine secretion. In addition, they modulate the osteoclast/osteoblast balance, by inducing osteoclast differentiation and inhibiting osteoblast function. Targeting either ligand or receptor reverses these effects, leading to in vivo tumor burden control and prevention of osteolysis, as confirmed in both murine and humanized mouse models. Expert opinion: These promising data set the stage for clinical trials to assess the effects of CCR1 inhibitors in MM. The success of these studies depends on the development of novel antagonists with improved chemical/physical properties and careful selection of the patient population who may benefit the most from these agents. C1 [Anderson, Kenneth C.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. [Vallet, Sonia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Vallet, Sonia] Univ Heidelberg, Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 92 TC 17 Z9 17 U1 0 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD SEP PY 2011 VL 15 IS 9 BP 1037 EP 1047 DI 10.1517/14728222.2011.586634 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 807MJ UT WOS:000293902300001 PM 21609295 ER PT J AU Johri, AM Rojas, CA El-Sherief, A Witzke, CF Chitty, DW Palacios, IF Passeri, JJ King, MEE Abbara, S AF Johri, Amer M. Rojas, Carlos A. El-Sherief, Ahmed Witzke, Christian F. Chitty, David W. Palacios, Igor F. Passeri, Jonathan J. King, Mary Etta E. Abbara, Suhny TI Imaging of atrial septal defects: echocardiography and CT correlation SO HEART LA English DT Article ID PATENT FORAMEN OVALE; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; SURGICAL-TREATMENT; COLOR DOPPLER; DIAGNOSIS; CONTRAST; STROKE; ADULTS C1 [Johri, Amer M.; Chitty, David W.] Queens Univ, Div Cardiol, Cardiovasc Imaging Network Queens, Kingston, ON, Canada. [Rojas, Carlos A.; El-Sherief, Ahmed; Abbara, Suhny] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Radiol,Heart Ctr, Boston, MA USA. [Witzke, Christian F.; Palacios, Igor F.; Passeri, Jonathan J.; King, Mary Etta E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Johri, AM (reprint author), Queens Univ, Div Cardiol, Cardiovasc Imaging Network Queens, 76 Stuart St,FAPC 3, Kingston, ON, Canada. EM amerschedule@gmail.com NR 24 TC 7 Z9 7 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD SEP PY 2011 VL 97 IS 17 BP 1441 EP 1453 DI 10.1136/hrt.2010.205732 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 803IS UT WOS:000293575600014 PM 21821635 ER PT J AU Alberts, MJ Bhatt, DL Smith, SC Rother, J Goto, S Hirsch, AT Steg, PG AF Alberts, Mark J. Bhatt, Deepak L. Smith, Sidney C., Jr. Roether, Joachim Goto, Shinya Hirsch, Alan T. Steg, Ph Gabriel CA REACH Registry Investigators TI Risk factors and outcomes for patients with vascular disease and serious bleeding events SO HEART LA English DT Article ID ACUTE CORONARY SYNDROMES; LOW-DOSE ASPIRIN; ANTITHROMBOTIC THERAPY; CARDIOVASCULAR-DISEASE; SECONDARY PREVENTION; PLATELET INHIBITION; ATRIAL-FIBRILLATION; CLINICAL-OUTCOMES; BLOOD-TRANSFUSION; ADVERSE EVENTS AB Objective To determine the risk and outcomes of serious bleeding events in patients with atherosclerotic vascular disease or risk factors. Methods 68 375 outpatients with prior ischaemic vascular events or multiple atherosclerotic risk factors were followed in this prospective observational study; 64 977 had 1-year follow-up data. Main outcome measures were rates of serious bleeding events and 1-year outcomes for patients with and without serious bleeding events. Results The 1-year rate of serious haemorrhage was 0.92%, with a cerebral haemorrhage rate of 0.11%. Patients with symptomatic vascular disease had a haemorrhage rate of 1.0%, compared with 0.59% in those with risk factors only. Risk factors for serious bleeding included age, smoking, hypertension, diabetes, congestive heart failure, use of antithrombotics and polyvascular disease. Bleeding risk increased with the use of anticoagulants (OR 1.99, 95% CI 1.38 to 2.86, p<0.001) or antiplatelet agents combined with anticoagulants (OR 2.54, 95% CI 1.74 to 3.71, p<0.001). By logistic regression analysis, patients with a serious bleed (excluding cerebral haemorrhage) had a more than threefold increased risk (HR 3.25, 95% CI 2.58 to 4.10, p<0.0001) of a significant vascular outcome (myocardial infarction, stroke, vascular death) compared with patients without a serious bleed. Conclusions Serious bleeding complications were relatively rare, but significant considering the large population at risk. Predictors of increased bleeding were similar to the risk factors for ischaemic events. Patients who experienced a serious bleed had a significantly higher rate of major vascular events. C1 [Alberts, Mark J.] Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. [Roether, Joachim] Asklepios Klin Altona, Dept Neurol, Hamburg, Germany. [Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Kanagawa 2591100, Japan. [Goto, Shinya] Tokai Univ, Sch Med, Metab Dis Ctr, Kanagawa 2591100, Japan. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Steg, Ph Gabriel] Univ Paris 07, INSERM, U698, AP HP, Paris, France. RP Alberts, MJ (reprint author), Northwestern Univ, Feinberg Sch Med, 710N Lake Shore Dr,Room 1420, Chicago, IL 60611 USA. EM m-alberts@northwestern.edu FU sanofi-aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); World Heart Federation; Boehringer-Ingelheim; Merck/Schering-Plough; Genentech; Pfizer; EKR Therapeutics; WebMD; Lundbeck; Eisai; Daiichi-Sankyo; GlaxoSmithKline; Otsuka; Bayer; Schering-Plough; Takeda; Astellas; AstraZeneca; Novartis; Kowa; Ono; Merck Sharpe and Dohme; Nycomed; Servier; Medicines Company; speakers bureau from Boehringer-Ingelheim; ZLB Behring FX The REACH Registry is sponsored by sanofi-aventis and Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). We also acknowledge statistical support by Francoise Calvi-Gries at sanofi-aventis. The REACH Registry enforces a no-ghost-writing policy. The first draft was written by Mark Alberts. We thank the REACH Editorial Support Group for providing editorial help and assistance in preparing this manuscript, including editing, checking content and language, formatting, referencing and preparing tables and figures.; The REACH Registry is endorsed by the World Heart Federation. The REACH Registry is sponsored by sanofi-aventis and Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan). The sponsors provide logistical support. All the publication activity is controlled by the REACH Registry Global Publication Committee (Ph Gabriel Steg (co-chair), Deepak L Bhatt (co-chair), Mark J Alberts, Ralph D'Agostino, Kim Eagle, Shinya Goto, Alan T Hirsch, Chisu-Suong Liau, Jean-Louis Mas, E Magnus Ohman, Joachim Rother, Sidney C Smith, Peter W F Wilson). All manuscripts in the REACH Registry are prepared by independent authors who are not governed by the funding sponsors and are reviewed by an academic publication committee before submission. The funding sponsors have the opportunity to review manuscript submissions but do not have authority to change any aspect of a manuscript.; MJA has received research grants, speaking honoraria and/or consulting fees from sanofi-aventis, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck/Schering-Plough, Genentech, Pfizer, EKR Therapeutics, WebMD and Lundbeck. He serves on a DSMB for Mitsubishi Pharma. DLB discloses the following relationships: research grants (significant): Astra Zeneca, Bristol-Myers Squibb, Eisai, sanofi-aventis, The Medicines Company. JR discloses the following relationships: speakers bureau (all modest): Boehringer-Ingelheim, Bristol-Myers Squibb, sanofi-aventis, Lundbeck; consulting/advisory board (all modest): Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, sanofi-aventis, Lundbeck. SG has received honoraria and consulting fees from Eisai, sanofi-aventis, Daiichi-Sankyo, GlaxoSmithKline, Bristol-Myers Squibb, Otsuka, Bayer, Schering-Plough, Takeda, Astellas, AstraZeneca, Novartis and Kowa; and research grants from Pfizer, Ono, Eisai, Otsuka, Daiichi-Sankyo, sanofi-aventis, Takeda and Astellas within the last 3 years. ATH has received research grants from Bristol-Myers Squibb and sanofi-aventis. PhGS has received honoraria for advisory board attendance and consulting fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharpe and Dohme, Nycomed, sanofi-aventis, Servier, Takeda, The Medicines Company; speakers bureau from Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Nycomed, sanofi-aventis, Servier, ZLB Behring; and research grant from sanofi-aventis within the last 3 years. NR 40 TC 9 Z9 9 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD SEP PY 2011 VL 97 IS 18 BP 1507 EP 1512 DI 10.1136/hrt.2010.221788 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 809HV UT WOS:000294043300010 PM 21715441 ER PT J AU Alemi, F Kwon, E Chiu, J Aoki, H Stewart, L Corvera, CU AF Alemi, Farzad Kwon, Edwin Chiu, Jonathan Aoki, Hisae Stewart, Lygia Corvera, Carlos U. TI Laparoscopic treatment of liver tumours using a two-needle probe bipolar radiofrequency ablation device SO HPB LA English DT Article DE hepatocellular carcinoma; liver resection; liver ID PERCUTANEOUS ETHANOL INJECTION; SMALL HEPATOCELLULAR-CARCINOMA; UNRESECTABLE TUMORS; HEPATIC RESECTION; PORCINE LIVER; HABIB(TM) 4X; IN-VIVO; COMPLICATIONS; METASTASES; CLASSIFICATION AB Background: Many hepatobiliary centres are increasingly utilizing thermocoagulative devices such as bipolar-radiofrequency ablation (B-RFA). Compared with monopolar-radiofrequency ablation (M-RFA), B-RFA does not require grounding pads, thereby avoiding dermal burn injuries, and does not position probes directly into the tumour but rather on the perimeter. Additionally, B-RFA can precoagulate parenchyma to assist in hepatic resection. Herein, we report our early experience using B-RFA. Methods: A retrospective review identified 68 patients who underwent M-RFA or B-RFA between June 2004 and September 2010 in an academic centre. Peri-operative metrics were analysed. Results: M-RFA was used to treat 30 patients, whereas B-RFA was used for 17 patients. There were no differences in peri-operative metrics, survival or disease recurrence between M-RFA and B-RFA. Seventeen additional patients underwent B-RFA precoagulation during laparoscopic resection (segmentectomy in eleven patients and multi-segmental resection in six patients). Four patients with multifocal disease underwent procedures that combined B-RFA with resection. Conclusions: The early experience utilizing B-RFA demonstrates equivalency to M-RFA with respect to peri-operative metrics and survival. Moreover, B-RFA can be utilized to precoagulate tissue during a planned resection, making it not only a useful tool for tumour therapy but also a useful adjunct during surgical resections. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Corvera, CU (reprint author), 4150 Clement St, San Francisco, CA 94121 USA. EM carlos.corvera@ucsfmedctr.org FU Veterans Health Administration; Northern California Institute for Research and Education FX A grant from the Veterans Health Administration and the Northern California Institute for Research and Education. Communication: Originally presented at Americas HPBA Conference March 2011, Miami, Fl USA. NR 33 TC 4 Z9 4 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1365-182X EI 1477-2574 J9 HPB JI HPB PD SEP PY 2011 VL 13 IS 9 BP 656 EP 664 DI 10.1111/j.1477-2574.2011.00347.x PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 807OR UT WOS:000293909800011 PM 21843267 ER PT J AU Russo, BC Horzempa, J O'Dee, DM Schmitt, DM Brown, MJ Carlson, PE Xavier, RJ Nau, GJ AF Russo, Brian C. Horzempa, Joseph O'Dee, Dawn M. Schmitt, Deanna M. Brown, Matthew J. Carlson, Paul E., Jr. Xavier, Ramnik J. Nau, Gerard J. TI A Francisella tularensis Locus Required for Spermine Responsiveness Is Necessary for Virulence SO INFECTION AND IMMUNITY LA English DT Article ID LIVE VACCINE STRAIN; IN-VIVO; SUBSP TULARENSIS; CBS DOMAINS; SCHU S4; INTRACELLULAR BACTERIUM; INTRAMACROPHAGE GROWTH; SALMONELLA-TYPHIMURIUM; PLASMODIUM-FALCIPARUM; EPITHELIAL-CELLS AB Tularemia is a debilitating febrile illness caused by the category A biodefense agent Francisella tularensis. This pathogen infects over 250 different hosts, has a low infectious dose, and causes high morbidity and mortality. Our understanding of the mechanisms by which F. tularensis senses and adapts to host environments is incomplete. Polyamines, including spermine, regulate the interactions of F. tularensis with host cells. However, it is not known whether responsiveness to polyamines is necessary for the virulence of the organism. Through transposon mutagenesis of F. tularensis subsp. holarctica live vaccine strain (LVS), we identified FTL_0883 as a gene important for spermine responsiveness. In-frame deletion mutants of FTL_0883 and FTT_0615c, the homologue of FTL_0883 in F. tularensis subsp. tularensis Schu S4 (Schu S4), elicited higher levels of cytokines from human and murine macrophages compared to wild-type strains. Although deletion of FTL_0883 attenuated LVS replication within macrophages in vitro, the Schu S4 mutant with a deletion in FTT_0615c replicated similarly to wild-type Schu S4. Nevertheless, both the LVS and the Schu S4 mutants were significantly attenuated in vivo. Growth and dissemination of the Schu S4 mutant was severely reduced in the murine model of pneumonic tularemia. This attenuation depended on host responses to elevated levels of proinflammatory cytokines. These data associate responsiveness to polyamines with tularemia pathogenesis and define FTL_0883/FTT_0615c as an F. tularensis gene important for virulence and evasion of the host immune response. C1 [Russo, Brian C.; Horzempa, Joseph; O'Dee, Dawn M.; Schmitt, Deanna M.; Brown, Matthew J.; Carlson, Paul E., Jr.; Nau, Gerard J.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA. [Nau, Gerard J.] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA. [Nau, Gerard J.] Univ Pittsburgh, Sch Med, Ctr Vaccine Res, Pittsburgh, PA 15261 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nau, GJ (reprint author), Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, W1157 BSTWR,200 Lothrop St, Pittsburgh, PA 15261 USA. EM gjnau@pitt.edu OI Nau, Gerard/0000-0001-7921-8317 FU NIH [AI074402]; University of Pittsburgh FX This study was funded by NIH grant AI074402 and institutional funding from the University of Pittsburgh. NR 65 TC 17 Z9 17 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2011 VL 79 IS 9 BP 3665 EP 3676 DI 10.1128/IAI.00135-11 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 807IV UT WOS:000293891000019 PM 21670171 ER PT J AU Jia, HB Liu, HX Kong, JY Hou, JB Wu, J Zhang, MM Tian, JW Liu, HM Ma, LJ Hu, SN Huang, XT Zhang, SS Zhang, SO Yu, B Jang, IK AF Jia, Haibo Liu, Haixia Kong, Junying Hou, Jingbo Wu, Jian Zhang, Maomao Tian, Jinwei Liu, Huimin Ma, Lijia Hu, Sining Huang, Xingtao Zhang, Shaosong Zhang, Shuo Yu, Bo Jang, Ik-Kyung TI A novel polymer-free paclitaxel-eluting stent with a nanoporous surface for rapid endothelialization and inhibition of intimal hyperplasia: Comparison with a polymer-based sirolimus-eluting stent and bare metal stent in a porcine model SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE polymer-free; drug-eluting stent; nanoporous surface; inflammation; optical coherence tomography; porcine ID OPTICAL COHERENCE TOMOGRAPHY; HYPERSENSITIVITY; IMPLANTATION; RESTENOSIS; RESPONSES; TRIAL AB Hypersensitivity and inflammatory responses to polymers may be responsible for late stent thrombosis after implantation of a drug-eluting stent (DES). Polymer-free DES may reduce the prevalence of these adverse reactions in vessels. We evaluated a polymer-free paclitaxel-eluting-stent with a nanoporous surface (nano-PES) for endothelialization and inhibition of neointimal hyperplasia by optical coherence tomography (OCT) and pathology in a porcine model. Nano-PES with high-dose (HD) and low-dose (LD) paclitaxel (1.0 mu g/mm(2) and 0.4 mu g/mm(2), respectively) was compared with a sirolimus-eluting stent (SES) and bare-metal stent (BMS) in a porcine model. Fifty-three stents (14 HD, 14 LD, 14 SES, 11 BMS) were implanted in 18 minipigs. At 14 days, nano-PES with HD and LD showed more complete endothelialization compared with SES. BMS had 100% endothelial coverage. At 28 days, a significant reduction in neointimal hyperplasia was detected by OCT in the nano-PES HD group compared with BMS. No benefit in prevention of the neointimal hyperplasia was observed in the nano-PES LD group. Nano-PES stents showed decreased deposition of fibrin and inflammation compared with SES. Pharmacokinetic studies revealed that nano-PES could effectively deliver the drug to the local coronary artery and it released the drug more rapidly than SES. Such a release profile was favorable for rapid endothelialization of nano-PES. The present study showed the nano-PES to be a new drug-delivery technology; that it used a nanoporous stent surface; that it offered desirable drug-elution properties without the use of polymers; that it may translate into an improved safety profile for next-generation DES. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 98A: 629-637, 2011. C1 [Jia, Haibo; Liu, Haixia; Kong, Junying; Hou, Jingbo; Wu, Jian; Zhang, Maomao; Tian, Jinwei; Liu, Huimin; Ma, Lijia; Hu, Sining; Huang, Xingtao; Zhang, Shuo; Yu, Bo] Harbin Med Coll, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. [Jia, Haibo; Liu, Haixia; Kong, Junying; Hou, Jingbo; Wu, Jian; Zhang, Maomao; Tian, Jinwei; Liu, Huimin; Ma, Lijia; Hu, Sining; Huang, Xingtao; Zhang, Shuo; Yu, Bo] Harbin Med Coll, Minist Educ, Key Lab Myocardial Ischemia Mech & Treatment, Harbin, Peoples R China. [Zhang, Shaosong] A St Jude Med Co, LightLab Imaging Inc, Westford, MA USA. [Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Yu, B (reprint author), Harbin Med Coll, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China. EM yubodr@163.com FU Science and Technology Key Project of Heilongjiang Province, China [GC10C305-3]; Educational Commission Major Project of Heilongjiang Province, China [11551z009]; National Natural Science Foundation of China [30871064/C140401]; Open Foundation of Key Laboratory of Myocardial Ischemia Mechanism and Treatment (Harbin Medical University), Ministry of Education [KF201007] FX Contract grant sponsor: Science and Technology Key Project of Heilongjiang Province, China; contract grant number: GC10C305-3; Contract grant sponsor: Educational Commission Major Project of Heilongjiang Province, China; contract grant number: 11551z009; Contract grant sponsor: National Natural Science Foundation of China; contract grant number: 30871064/C140401; Contract grant sponsor: Open Foundation of Key Laboratory of Myocardial Ischemia Mechanism and Treatment (Harbin Medical University), Ministry of Education; contract grant number: KF201007 NR 17 TC 9 Z9 12 U1 2 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD SEP PY 2011 VL 98A IS 4 BP 629 EP 637 DI 10.1002/jbm.a.33151 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 806XJ UT WOS:000293850500017 PM 21732525 ER PT J AU Arai, K Lok, J Guo, SZ Hayakawa, K Xing, CH Lo, EH AF Arai, Ken Lok, Josephine Guo, Shuzhen Hayakawa, Kazuhide Xing, Changhong Lo, Eng H. TI Cellular Mechanisms of Neurovascular Damage and Repair After Stroke SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE stroke; neurovascular unit; brain remodeling; neurovascular signaling; biphasic response ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; OLIGODENDROCYTE PRECURSOR CELLS; MATRIX METALLOPROTEINASES; ENDOTHELIAL-CELLS; RAT-BRAIN; SUBVENTRICULAR ZONE; TEMPORAL PROFILE; ANGIOGENESIS; MATRIX-METALLOPROTEINASE-9 AB The biological processes underlying stroke are complex, and patients have a narrow repertoire of therapeutic opportunities. After the National Institutes of Health (NIH) convened the Stroke Progress Review Group in 2001, stroke research shifted from having a purely neurocentric focus to adopting a more integrated view wherein dynamic interactions between all cell types contribute to function and dysfunction in the brain. This so-called "neurovascular unit" provides a conceptual framework that emphasizes cell-cell interactions between neuronal, glial, and vascular elements. Under normal conditions, signaling within the neurovascular unit helps maintain homeostasis. After stroke, cell-cell signaling is disturbed, leading to pathophysiology. More recently, emerging data now suggest that these cell-cell signaling mechanisms may also mediate parallel processes of neurovascular remodeling during stroke recovery. Because plasticity is a signature feature of the young and developing brain, these concepts may have special relevance to how the pediatric brain responds after stroke. C1 [Arai, Ken; Lok, Josephine; Guo, Shuzhen; Hayakawa, Kazuhide; Xing, Changhong; Lo, Eng H.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Arai, Ken; Lok, Josephine; Guo, Shuzhen; Hayakawa, Kazuhide; Xing, Changhong; Lo, Eng H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Arai, Ken; Lok, Josephine; Guo, Shuzhen; Hayakawa, Kazuhide; Xing, Changhong; Lo, Eng H.] Harvard Univ, Sch Med, Boston, MA USA. RP Arai, K (reprint author), Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM karai@partners.org FU Deane Foundation; American Heart Association; National Institutes of Health [5R13NS040925-09]; National Institutes of Health Office of Rare Diseases Research; Child Neurology Society; Children's Hemiplegia and Stroke Association FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: Supported in part by the Deane Foundation, the American Heart Association, and National Institutes of Health. Supported by grants from the National Institutes of Health (5R13NS040925-09), the National Institutes of Health Office of Rare Diseases Research, the Child Neurology Society, and the Children's Hemiplegia and Stroke Association. NR 56 TC 33 Z9 36 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 2011 VL 26 IS 9 BP 1193 EP 1198 DI 10.1177/0883073811408610 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 807JH UT WOS:000293892500014 PM 21628695 ER PT J AU Le Norcy, E Kwak, SY Wiedemann-Bidlack, FB Beniash, E Yamakoshi, Y Simmer, JP Margolis, HC AF Le Norcy, E. Kwak, S-Y Wiedemann-Bidlack, F. B. Beniash, E. Yamakoshi, Y. Simmer, J. P. Margolis, H. C. TI Leucine-rich Amelogenin Peptides Regulate Mineralization in vitro SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE amelogenin; calcium; enamel; LRAP; mineralization; self-assembly ID CALCIUM-PHOSPHATE; ENAMEL MATRIX; HYDROXYAPATITE CRYSTALS; C-TERMINUS; LRAP; PHENOTYPE; PHOSPHORYLATION; AGGREGATION; IMPERFECTA; BOVINE AB Amelogenin's capacity to regulate enamel formation is related to its conserved N- and C-terminal domains, its ability to self-assemble, and its ability to stabilize amorphous calcium phosphate (ACP) - a capacity enhanced by amelogenin phosphorylation. This in vitro study provides further insight into amelogenin function, using variations of the Leucine-Rich Amelogenin Peptide (LRAP), an alternative splice product comprised solely of amelogenin's N- and C-terminal domains. Peptide self-assembly was studied by dynamic light-scattering and transmission electron microscopy (TEM). TEM, selected area electron diffraction, and Fourier transform-infrared spectroscopy were also used to determine the effect of phosphorylated and non-phosphorylated LRAP on calcium phosphate formation. Results show that phosphorylated and non-phosphorylated LRAP can self-assemble into chain-like structures in a fashion dependent on the C-terminal domain. Notably, this capacity was enhanced by added calcium and to a much greater degree for phosphorylated LRAP. Furthermore, phosphorylated LRAP was found to stabilize ACP and prevent its transformation to hydroxyapatite (HA), while aligned HA crystals formed in the presence of non-phosphorylated LRAP. The N- and C-terminal amelogenin domains in non-phosphorylated LRAP are, therefore, sufficient to guide ACP transformation into ordered bundles of apatite crystals, making LRAP an excellent candidate for biomimetic approaches for enamel regeneration. C1 [Le Norcy, E.; Kwak, S-Y; Wiedemann-Bidlack, F. B.; Margolis, H. C.] Forsyth Inst, Dept Biomineralizat, Cambridge, MA 02142 USA. [Le Norcy, E.; Kwak, S-Y; Wiedemann-Bidlack, F. B.; Margolis, H. C.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA USA. [Beniash, E.] Univ Pittsburgh, Dept Oral Biol, Pittsburgh, PA 15260 USA. [Yamakoshi, Y.; Simmer, J. P.] Univ Michigan, Dent Res Lab, Ann Arbor, MI 48109 USA. RP Margolis, HC (reprint author), Forsyth Inst, Dept Biomineralizat, 245 1st St, Cambridge, MA 02142 USA. EM hmargolis@forsyth.org FU NIDCR [R01-DE016376] FX This work was supported by NIDCR grant R01-DE016376 (HCM). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 30 TC 22 Z9 22 U1 0 U2 20 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 2011 VL 90 IS 9 BP 1091 EP 1097 DI 10.1177/0022034511411301 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 807FT UT WOS:000293882400008 PM 21653221 ER PT J AU Lynch, CP Egede, LE AF Lynch, Cheryl P. Egede, Leonard E. TI Optimizing Diabetes Self-care in Low Literacy and Minority Populations-Problem-solving, Empowerment, Peer Support and Technology-based Approaches SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED-TRIAL; HEALTH LITERACY; MANAGEMENT; INTERVENTIONS; VETERANS; OUTCOMES; AFFAIRS C1 [Lynch, Cheryl P.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Lynch, Cheryl P.; Egede, Leonard E.] Ralph H Johnson VAMC, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. [Lynch, Cheryl P.; Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU NIDDK NIH HHS [K24 DK093699] NR 25 TC 7 Z9 7 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2011 VL 26 IS 9 BP 953 EP 955 DI 10.1007/s11606-011-1759-9 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 808WW UT WOS:000294013700004 PM 21647745 ER PT J AU Morasco, BJ Duckart, JP Dobscha, SK AF Morasco, Benjamin J. Duckart, Jonathan P. Dobscha, Steven K. TI Adherence to Clinical Guidelines for Opioid Therapy for Chronic Pain in Patients with Substance Use Disorder SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE chronic pain; substance use disorder; opioids; treatment guidelines; medical utilization ID CHRONIC NONCANCER PAIN; LOW-BACK-PAIN; PRIMARY-CARE; ADMINISTRATIVE DATA; MEDICATION MISUSE; MANAGEMENT; HEALTH; PRESCRIPTIONS; COMORBIDITY; IMPROVEMENT AB BACKGROUND: Patients with chronic non-cancer pain (CNCP) have high rates of substance use disorders (SUD). SUD complicates pain treatment and may lead to worse outcomes. However, little information is available describing adherence to opioid treatment guidelines for CNCP generally, or guideline adherence for patients with comorbid SUD. OBJECTIVE: Examine adherence to clinical guidelines for opioid therapy over 12 months, comparing patients with SUD diagnoses made during the prior year to patients without SUD. DESIGN: Cohort study. PARTICIPANTS: Administrative data were collected from veterans with CNCP receiving treatment within a Veterans Affairs regional healthcare network who were prescribed chronic opioid therapy in 2008 (n = 5814). KEY RESULTS: Twenty percent of CNCP patients prescribed chronic opioid therapy had a prior-year diagnosis of SUD. Patients with SUD were more likely to have pain diagnoses and psychiatric comorbidities. In adjusted analyses, patients with SUD were more likely than those without SUD to have had a mental health appointment (29.7% versus 17.2%, OR = 1.49, 95% CI = 1.26-1.77) and a urine drug screen (UDS) (47.0% versus 18.2%, OR = 3.53, 95% CI = 3.06-4.06) over 12 months. There were no significant differences between groups on receiving more intensive treatment in primary care (63.4% versus 61.0%), long-acting opioids (26.9% versus 26.0%), prescriptions for antidepressants (88.2% versus 85.8%, among patients with depression), or participating in physical therapy (30.6% versus 28.6%). Only 35% of patients with SUD received substance abuse treatment. CONCLUSIONS: CNCP patients with SUD were more likely to have mental health appointments and receive UDS monitoring, but not more likely to participate in other aspects of pain care compared to those without SUD. Given data suggesting patients with comorbid SUD may need more intensive treatment to achieve improvements in pain-related function, SUD patients may be at high risk for poor outcomes. C1 [Morasco, Benjamin J.; Dobscha, Steven K.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Morasco, Benjamin J.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Duckart, Jonathan P.; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr R&D99, Mental Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR USA. EM benjamin.morasco@va.gov FU National Institute on Drug Abuse [K23DA023467]; VA Health Services Research and Development service [REA 06174]; Oregon Clinical and Translational Research Institute; National Center for Research Resources, a component of the National Institutes of Health and NIH Roadmap for Medical Research [Ul1RR024140] FX This study was supported in part by award K23DA023467 from the National Institute on Drug Abuse to Dr. Morasco. Jonathan Duckart, MPS, was supported by grant REA 06174 from the VA Health Services Research and Development service. The authors appreciate support provided from the Oregon Clinical and Translational Research Institute, grant number Ul1RR024140 from the National Center for Research Resources, a component of the National Institutes of Health and NIH Roadmap for Medical Research. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health or the Department of Veterans Affairs. NR 42 TC 29 Z9 29 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2011 VL 26 IS 9 BP 965 EP 971 DI 10.1007/s11606-011-1734-5 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 808WW UT WOS:000294013700008 PM 21562923 ER PT J AU Wang, EA McGinnis, KA Fiellin, DA Goulet, JL Bryant, K Gibert, CL Leaf, DA Mattocks, K Sullivan, LE Vogenthaler, N Justice, AC AF Wang, Emily A. McGinnis, Kathleen A. Fiellin, David A. Goulet, Joseph L. Bryant, Kendall Gibert, Cynthia L. Leaf, David A. Mattocks, Kristin Sullivan, Lynn E. Vogenthaler, Nicholas Justice, Amy C. CA VACS Project Team TI Food Insecurity is Associated with Poor Virologic Response among HIV-Infected Patients Receiving Antiretroviral Medications SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE food insecurity; HIV; patients; antiretrovirals ID HOUSING INSTABILITY; ALCOHOL-CONSUMPTION; WELFARE RECIPIENTS; PHARMACY RECORDS; MENTAL-HEALTH; SAN-FRANCISCO; WEIGHT-LOSS; ADHERENCE; HIV/AIDS; INSUFFICIENCY AB BACKGROUND AND OBJECTIVE: Food insecurity negatively impacts HIV disease outcomes in international settings. No large scale U.S. studies have investigated the association between food insecurity and severity of HIV disease or the mechanism of this possible association. The objective of this study was to examine the impact of food insecurity on HIV disease outcomes in a large cohort of HIV-infected patients receiving antiretroviral medications. DESIGN: This is a cross-sectional study. PARTICIPANTS AND SETTING: Participants were HIV-infected patients enrolled in the Veterans Aging Cohort Study between 2002-2008 who were receiving antiretroviral medications. MAIN MEASUREMENTS: Participants reporting "concern about having enough food for you or your family in the past 30 days" were defined as food insecure. Using multivariable logistic regression, we explored the association between food insecurity and both low CD4 counts (< 200 cells/mu L) and unsuppressed HIV-1 RNA (> 500 copies/mL). We then performed mediation analysis to examine whether antiretroviral adherence or body mass index mediates the observed associations. KEY RESULTS: Among 2353 HIV-infected participants receiving antiretroviral medications, 24% reported food insecurity. In adjusted analyses, food insecure participants were more likely to have an unsuppressed HIV-1 RNA (AOR 1.37, 95% CI 1.09, 1.73) compared to food secure participants. Mediation analysis revealed that neither antiretroviral medication adherence nor body mass index contributes to the association between food insecurity and unsuppressed HIV-1 RNA. Food insecurity was not independently associated with low CD4 counts. CONCLUSIONS: Among HIV-infected participants receiving antiretroviral medications, food insecurity is associated with unsuppressed viral load and may render treatment less effective. Longitudinal studies are needed to test the potential causal association between food insecurity, lack of virologic suppression, and additional HIV outcomes. C1 [Wang, Emily A.; Fiellin, David A.; Goulet, Joseph L.; Mattocks, Kristin; Sullivan, Lynn E.; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [McGinnis, Kathleen A.] Pittsburgh VA Healthcare Syst, Pittsburgh, PA USA. [Goulet, Joseph L.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Bryant, Kendall] NIAAA, NIH, Rockville, MD 20852 USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Gibert, Cynthia L.] VA Med Ctr, Washington, DC USA. [Leaf, David A.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Vogenthaler, Nicholas] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA. RP Wang, EA (reprint author), Yale Univ, Sch Med, Dept Internal Med, Harkness Hall Bldg A 367 Cedar St,Suite 410A, New Haven, CT 06510 USA. EM emily.wang@yale.edu RI Nguyen, Giang/D-9027-2016; OI Goulet, Joseph/0000-0002-0842-804X; Fiellin, David/0000-0002-4006-010X FU National Institute on Alcohol and Alcohol Abuse [U01 AA 13566, U10 AA 13566]; National Institute of Aging [K23 AG00826]; Robert Wood Johnson Generalist Faculty Scholar Award; NIA; National Institute of Mental Health; VA HSR&D Research Enhancement Award Program (REAP) PRIME Project [REA 08-266] FX This work was funded by National Institute on Alcohol and Alcohol Abuse (U01 AA 13566 and U10 AA 13566), National Institute of Aging (K23 AG00826), Robert Wood Johnson Generalist Faculty Scholar Award, an Inter-agency Agreement between NIA, National Institute of Mental Health, and VA HSR&D Research Enhancement Award Program (REAP) PRIME Project (REA 08-266). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 36 TC 41 Z9 41 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2011 VL 26 IS 9 BP 1012 EP 1018 DI 10.1007/s11606-011-1723-8 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 808WW UT WOS:000294013700015 PM 21573882 ER PT J AU Wong, HJ Morra, D AF Wong, Hannah J. Morra, Dante TI Excellent Hospital Care for All: Open and Operating 24/7 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE nights and weekend; hospital care; quality and safety; efficiency ID WEEKDAY ADMISSION; OF-CARE; WEEKEND; MORTALITY; RATES; SATISFACTION; OUTCOMES; NURSES; MODEL; UNIT AB Nights and weekends are the times when most people are admitted to the hospital. They are also synonymous with reduced staffing levels and fewer specialized diagnostic, procedural, and treatment options. Indeed, there is increasing evidence suggesting that patient care is compromised during these times. Equally important is the inefficient use of capital investments during nights and weekends, and inappropriate utilization of hospital beds caused by poor weekend discharge flexibility. We believe that these findings should be of concern not just to hospital care providers, but across care settings and to the general public. In this perspective article, we highlight how our current office-hours system of running hospitals threatens the lives of our sickest, most vulnerable patients, describe solutions currently implemented in hospitals that may alleviate this disparity, and discuss challenges to wider scale implementation. C1 [Morra, Dante] Toronto Gen Hosp, Toronto, ON M5G 2C4, Canada. [Wong, Hannah J.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Wong, Hannah J.] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Wong, Hannah J.] Harvard Univ, Sch Med, Boston, MA USA. [Wong, Hannah J.; Morra, Dante] Univ Hlth Network, Ctr Innovat Complex Care, Toronto, ON, Canada. [Morra, Dante] Univ Toronto, Dept Med, Div Gen Internal Med, Univ Hlth Network, Toronto, ON, Canada. RP Morra, D (reprint author), Toronto Gen Hosp, 200 Elizabeth St,EN 14-218, Toronto, ON M5G 2C4, Canada. EM dante.morra@utoronto.ca OI Wong, Hannah/0000-0002-9740-0312 NR 28 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2011 VL 26 IS 9 BP 1050 EP 1052 DI 10.1007/s11606-011-1715-8 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 808WW UT WOS:000294013700019 PM 21499824 ER PT J AU Melrose, RJ Ettenhofer, ML Harwood, D Achamallah, N Campa, O Mandelkern, M Sultzer, DL AF Melrose, Rebecca J. Ettenhofer, Mark L. Harwood, Dylan Achamallah, Natalie Campa, Olivia Mandelkern, Mark Sultzer, David L. TI Cerebral Metabolism, Cognition, and Functional Abilities in Alzheimer Disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE Alzheimer disease; IADLs; functional ability; cerebral metabolism; cognition ID PREDICT INSTRUMENTAL ACTIVITIES; DORSOLATERAL PREFRONTAL CORTEX; POSTERIOR PARIETAL CORTEX; MINI-MENTAL-STATE; SHORT-TERM-MEMORY; EXECUTIVE DYSFUNCTION; NEUROPSYCHOLOGICAL PERFORMANCE; MILD DEMENTIA; OLDER-ADULTS; IMPAIRMENT AB Patients with Alzheimer disease (AD) exhibit profound difficulties in completing instrumental activities of daily living (IADLs), such as managing finances, organizing medications, and food preparation. It is unclear which brain areas underlie IADL deficits in AD. To address this question, we used voxel-based analysis to correlate the performance of IADLs with resting cerebral metabolism as measured during [F-18] fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in 44 patients with AD. Poorer ability to complete IADLs was associated with hypometabolism in right-sided cortical regions, including the parietal lobe, posterior temporal cortex, dorsolateral prefrontal cortex, and frontal pole. Follow-up path analyses examining anatomically defined regions of interest (ROI) demonstrated that the association between metabolism and IADLs was mediated by global cognition in frontal ROIs, and partially mediated by global cognition in the parietal ROI. Findings suggest that hypometabolism of right sided brain regions involved in executive functioning, visuospatial processing, attention, and working memory underlie functional impairments in patients with AD. C1 [Melrose, Rebecca J.; Harwood, Dylan; Achamallah, Natalie; Campa, Olivia; Sultzer, David L.] VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, Los Angeles, CA 90073 USA. [Melrose, Rebecca J.; Harwood, Dylan; Sultzer, David L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Ettenhofer, Mark L.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Mandelkern, Mark] VA Greater Los Angeles Healthcare Syst, Nucl Med Serv, Los Angeles, CA 90073 USA. [Mandelkern, Mark] Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Melrose, RJ (reprint author), VA Greater Los Angeles Healthcare Syst, Brain Behav & Aging Res Ctr, 11301 Wilshire Blvd,116AE, Los Angeles, CA 90073 USA. EM rjmelrose@ucla.edu FU Forest Research Institute; Department of Veterans Affairs; Office of RD; Office of Academic Affiliations; NIMH [R01MH56031] FX We thank Theresa Khoo for her assistance with formatting this manuscript. Dr Sultzer has received research grant support from Forest Research Institute. Potential conflicts to study participants were disclosed. None of the other authors report conflicts of interest.; The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: funded by the Department of Veterans Affairs (the Office of R&D, Merit Review, Career Development Award to R. Melrose; Office of Academic Affiliations, Special Fellowship Program in Advanced Geriatrics) and NIMH (R01MH56031). Study activities took place at the VA and the study was reviewed and approved by the VA and UCLA IRBs. It was presented in poster form at the American Association for Geriatric Psychiatry in Spring 2009. NR 70 TC 20 Z9 21 U1 4 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 EI 1552-5708 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2011 VL 24 IS 3 BP 127 EP 134 DI 10.1177/0891988711405333 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 809JS UT WOS:000294050600002 PM 21856969 ER PT J AU Teng, E Melrose, RJ Osato, S Jimenez, E Ercoli, LM Jarvik, LF AF Teng, Edmond Melrose, Rebecca J. Osato, Sheryl Jimenez, Elvira Ercoli, Linda M. Jarvik, Lissy F. TI Increasing Depressive Symptoms in Children of Alzheimer Parents SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE Alzheimer disease; offspring; longitudinal; depression ID MIDDLE-AGED CHILDREN; COGNITIVE DECLINE; RISK-FACTOR; RATING-SCALE; NEUROCOGNITIVE PERFORMANCE; HAMILTON DEPRESSION; FAMILY-HISTORY; OLDER-ADULTS; DISEASE; DEMENTIA AB Children of persons with Alzheimer disease (AD) are at increased risk of developing AD themselves, but specific factors that predict AD in this population have yet to be elucidated. Various studies indicate depressive symptoms may predate clinical AD and represent a risk factor and/or prodrome of incipient dementia, but their relevance for AD offspring remains uncertain. As part of a longitudinal family study of AD, we assessed depressive symptomatology in 30 middle aged AD offspring (mean age at baseline: 41.2). Their mean total scores on the Hamilton Depression Rating scale increased from 1.8 to 5.3 (P < .001) across a 20-year interval. Neurocognitive performance remained stable in a subset of this cohort (N = 25) over the same interval. Findings from this small convenience sample suggest emerging depressive symptoms may be among the earliest signs of subsequent dementia in this high-risk population but require confirmation through further longitudinal follow-up and replication in larger populations. C1 [Teng, Edmond; Melrose, Rebecca J.; Osato, Sheryl; Jimenez, Elvira; Jarvik, Lissy F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Teng, Edmond; Jimenez, Elvira] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Melrose, Rebecca J.; Osato, Sheryl; Jimenez, Elvira; Ercoli, Linda M.; Jarvik, Lissy F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Ercoli, Linda M.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. RP Teng, E (reprint author), W Los Angeles VA Healthcare Ctr, Neurobehav Unit, Bldg 401 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu FU Albert Parvin Foundation; Lon V. Smith Foundation; NIA [K08 AG34628]; AFAR; John A. Hartford Foundation; Atlantic Philanthropies, Starr Foundation FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Albert Parvin Foundation and the Lon V. Smith Foundation. ET is also supported by K08 AG34628 (jointly sponsored by the NIA, AFAR, John A. Hartford Foundation, Atlantic Philanthropies, Starr Foundation, and an anonymous donor). NR 59 TC 0 Z9 0 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2011 VL 24 IS 3 BP 135 EP 141 DI 10.1177/0891988711409402 PG 7 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 809JS UT WOS:000294050600003 PM 21633123 ER PT J AU Xu, J Lai, KKY Verlinsky, A Lugea, A French, SW Cooper, MP Ji, C Tsukamoto, H AF Xu, Jun Lai, Keane K. Y. Verlinsky, Alla Lugea, Aurelia French, Samuel W. Cooper, Marcus P. Ji, Cheng Tsukamoto, Hidekazu TI Synergistic steatohepatitis by moderate obesity and alcohol in mice despite increased adiponectin and p-AMPK SO JOURNAL OF HEPATOLOGY LA English DT Article DE Synergistic steatohepatitis; Obesity and alcohol synergism; Apoptosis; Necrosis; Macrophage activation; Nitrosative stress ID ENDOPLASMIC-RETICULUM STRESS; INDUCED INSULIN-RESISTANCE; FATTY LIVER-DISEASES; NITRIC-OXIDE; ER STRESS; MITOCHONDRIAL DYSFUNCTION; HEPATIC STEATOSIS; OXIDATIVE STRESS; UNITED-STATES; IN-VIVO AB Background & Aims: Mechanisms underlying synergistic liver injury caused by alcohol and obesity are not clear. We have produced a mouse model of synergistic steatohepatitis by recapitulating the natural history of the synergism seen in patients for mechanistic studies. Methods: Moderate obesity was induced in mice by 170% overnutrition in calories using intragastric overfeeding of high fat diet. Alcohol (low or high dose) was then co-administrated to determine its effects. Results: Moderate obesity plus alcohol intake causes synergistic steatohepatitis in an alcohol dose-dependent manner. A heightened synergism is observed when a high alcohol dose (32 g/kg/d) is used, resulting in plasma ALT reaching 392 +/- 28 U/L, severe steatohepatitis with pericellular fibrosis, marked M1 macrophage activation, a 40-fold induction of iNos, and intensified nitrosative stress in the liver. Hepatic expression of genes for mitochondrial biogenesis and metabolism are significantly downregulated, and hepatic ATP level is decreased. Synergistic ER stress evident by elevated XBP-1, GRP78 and CHOP is accompanied by hyperhomocysteinemia. Despite increased caspase 3/7 cleavage, their activities are decreased in a redox-dependent manner. Neither increased PARP cleavage nor TUNEL positive hepatocytes are found, suggesting a shift of apoptosis to necrosis. Surprisingly, the synergism mice have increased plasma adiponectin and hepatic p-AMPK, but adiponectin resistance is shown downstream of p-AMPK. Conclusions: Nitrosative stress mediated by M1 macrophage activation, adiponectin resistance, and accentuated ER and mitochondrial stress underlie potential mechanisms for synergistic steatohepatitis caused by moderate obesity and alcohol. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Xu, Jun; Lai, Keane K. Y.; Verlinsky, Alla; Lugea, Aurelia; French, Samuel W.; Tsukamoto, Hidekazu] Univ So Calif, Keck Sch Med, Dept Pathol, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA 90089 USA. [Lugea, Aurelia; Tsukamoto, Hidekazu] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [French, Samuel W.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Cooper, Marcus P.] Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA. [Ji, Cheng] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90089 USA. RP Xu, J (reprint author), Univ So Calif, Keck Sch Med, Dept Pathol, So Calif Res Ctr ALPD & Cirrhosis, 1333 San Pablo St,MMR 428, Los Angeles, CA 90089 USA. EM junx@usc.edu FU NIH (Southern California Research Center for ALPD and Cirrhosis, Animal Core, and Morphology Core) [P50AA011999, R24AA012885, 2R01AA014428-06A1]; Medical Research Service of Department of Veterans Affairs; Suntory Holdings, Inc.; NIAAA [T32AA007578] FX The authors thank Hasmik Mkrtchyan, Akiko Ueno, and Hongyun She for their outstanding technical support. The present study was supported by NIH Grants, P50AA011999 (Southern California Research Center for ALPD and Cirrhosis, Animal Core, and Morphology Core), R24AA012885 (Non-Parenchymal Liver Cell Core), 2R01AA014428-06A1 (to C. Ji), Medical Research Service of Department of Veterans Affairs, and Suntory Holdings, Inc. Jun Xu and Keane Lai are both supported by the NIAAA Institutional Training grant (T32AA007578). NR 51 TC 51 Z9 51 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD SEP PY 2011 VL 55 IS 3 BP 673 EP 682 DI 10.1016/j.jhep.2010.12.034 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 807VH UT WOS:000293930600024 PM 21256905 ER PT J AU Villanueva, A Hoshida, Y AF Villanueva, Augusto Hoshida, Yujin TI Depicting the role of TP53 in hepatocellular carcinoma progression SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID MOLECULAR CLASSIFICATION; P53; TARGETS; GENE AB Background & Aims: Mutations in TP53, a tumor suppressor gene, are associated with prognosis of many cancers. However, the prognostic values of TP53 mutation sites are not known for patients with hepatocellular carcinoma (HCC) because of heterogeneity in their geographic and etiologic backgrounds. Methods: TP53 mutations were investigated in a total of 409 HCC patients, including Chinese (n = 336) and white (n = 73) patients, using the direct sequencing method. Results: A total of 125 TP53 mutations were found in Chinese patients with HCC (37.2%). HCC patients with TP53 mutations had a shorter overall survival time compared with patients with wild-type TP53 (hazard ratio [HR], 1.86; 95% confidence interval [Cl]: 1.37-2.52; P<.001). The hot spot mutations R249S and V157F were significantly associated with worse prognosis in univariate (HR, 2.11; 95% Cl: 1.51-2.94; P < .001) and multivariate analyses (HR, 1.79; 95% Cl: 1.29-2.51; P < .001). Gene expression analysis revealed the existence of stem cell-like traits in tumors with TP53 mutations. These findings were validated in breast and lung tumor samples with TP53 mutations. Conclusions: TP53 mutations, particularly the hot spot mutations R2495 and V157F, are associated with poor prognosis for patients with HCC. The acquisition of stem cell-like gene expression traits might contribute to the aggressive behavior of tumors with TP53 mutation. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 [Villanueva, Augusto] Hosp Clin Barcelona, Barcelona Clin Liver Canc Grp, HCC Translat Res Lab, IDIBAPS,Liver Unit, Barcelona, Spain. [Villanueva, Augusto] Inst Carlos III, CIBEREHD, Barcelona, Spain. [Hoshida, Yujin] Broad Inst, Canc Program, Cambridge, MA USA. [Hoshida, Yujin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Villanueva, A (reprint author), Hosp Clin Barcelona, Barcelona Clin Liver Canc Grp, HCC Translat Res Lab, IDIBAPS,Liver Unit, Barcelona, Spain. EM augusto.villanueva@ciberehd.org RI Augusto, Villanueva/F-9378-2012 OI Augusto, Villanueva/0000-0003-3585-3727 NR 12 TC 13 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD SEP PY 2011 VL 55 IS 3 BP 724 EP 725 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 807VH UT WOS:000293930600030 PM 21616106 ER PT J AU Zhi, L Kim, P Thompson, BD Pitsillides, C Bankovich, AJ Yun, SH Lin, CP Cyster, JG Wu, MX AF Zhi, Liang Kim, Pilhan Thompson, Brian D. Pitsillides, Costas Bankovich, Alexander J. Yun, Seok-Hyun Lin, Charles P. Cyster, Jason G. Wu, Mei X. TI FTY720 Blocks Egress of T Cells in Part by Abrogation of Their Adhesion on the Lymph Node Sinus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SPHINGOSINE 1-PHOSPHATE RECEPTOR-1; TRANSENDOTHELIAL MIGRATION; IMMUNOSUPPRESSANT FTY720; ALPHA-I; MICE; AGONISTS; PROTEIN; S1P(1); ENTRY; RECIRCULATION AB Egress of lymphocytes from lymphoid tissues is a complex process in which G alpha i-mediated signals play a decisive role. We show here that although FTY720, an agonist of the sphingosine 1-phosphate (S1P)(1) receptor, induces S1P(1) receptor internalization sufficiently in the presence or absence of G alpha i2 or G alpha i3, the drug blocks egress of wild-type (WT) and G alpha i3-deficent T cells, but not G alpha i2-deficient T cells, in both WT and G alpha i2-deficient hosts. Intravital imaging of lymph nodes revealed that all three groups of T cells approached and engaged cortical sinusoids similarly in the presence or absence of FTY720. The cells also entered and departed the sinus at an almost identical frequency in the absence of the drug. However, after engagement of the sinus, most WT and G alpha i3-deficient T cells retracted and migrated back into the parenchyma in FTY720-treated animals, due to a failure of the cells to establish adhesion on the sinus, whereas G alpha i2-deficient T cells adhered firmly on the sinus, which prevented their retraction, facilitating their transmigration of the lymphatic endothelial barrier. These data confirm egress of G alpha i2(-/-) T cells independent of S1P-mediated chemotaxis and failure of FTY720 to close lymphatic stromal channels and argue for the first time, to our knowledge, that FTY720 induces lymphopenia in part by impairing T cell adhesion to the sinus in a manner dependent on G alpha i2. The Journal of Immunology, 2011, 187: 2244-2251. C1 [Zhi, Liang; Kim, Pilhan; Thompson, Brian D.; Pitsillides, Costas; Yun, Seok-Hyun; Lin, Charles P.; Wu, Mei X.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Zhi, Liang; Kim, Pilhan; Thompson, Brian D.; Pitsillides, Costas; Yun, Seok-Hyun; Lin, Charles P.; Wu, Mei X.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Bankovich, Alexander J.; Cyster, Jason G.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. [Bankovich, Alexander J.; Cyster, Jason G.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 55 Fruit St,Edwards 222, Boston, MA 02114 USA. EM mwu2@partners.org RI Kim, Pilhan/C-1836-2011; OI Kim, Pilhan/0000-0001-8388-1840; Bankovich, Alexander/0000-0003-2368-4479 FU National Institutes of Health [AI050822, AI070785]; Crohn's & Colitis Foundation of America FX This work was supported by National Institutes of Health Grants AI050822 and AI070785 and a Senior Research award from the Crohn's & Colitis Foundation of America (to M.X.W.). NR 35 TC 16 Z9 18 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2011 VL 187 IS 5 BP 2244 EP 2251 DI 10.4049/jimmunol.1100670 PG 8 WC Immunology SC Immunology GA 809MD UT WOS:000294059500028 PM 21788441 ER PT J AU Radebe, M Nair, K Chonco, F Bishop, K Wright, JK van der Stok, M Bassett, IV Mncube, Z Altfeld, M Walker, BD Ndung'u, T AF Radebe, Mopo Nair, Kriebashnie Chonco, Fundisiwe Bishop, Karen Wright, Jaclyn K. van der Stok, Mary Bassett, Ingrid V. Mncube, Zenele Altfeld, Marcus Walker, Bruce D. Ndung'u, Thumbi TI Limited Immunogenicity of HIV CD8(+) T-Cell Epitopes in Acute Clade C Virus Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID VIRAL LOAD; IMMUNE-RESPONSES; DISEASE PROGRESSION; RHESUS-MONKEYS; AIDS VACCINE; DOUBLE-BLIND; SET-POINT; VIREMIA; TRIAL; REPLICATION AB Background. Human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) responses contribute to the decline in acute peak viremia following infection. However, data on the relative immunogenicity of CD8(+) T-cell epitopes during and after acute viremia are lacking. Methods. We characterized CD8(+) T-cell responses in 20 acutely infected, antiretroviral-naive individuals with HIV-1 subtype C infection using the interferon-gamma enzyme-linked immunosorbent spot assay. Eleven of these had not fully seroconverted at the time of analysis. Viruses from plasma were sequenced within defined cytotoxic T-lymphocyte (CTL) cell epitopes for selected subjects. Results. At approximately 28 days after estimated initial infection, CD8(+) T-cell responses were directed against an average of 3 of the 410 peptides tested (range, 0-6); 2 individuals had no detectable responses at this time. At 18 weeks, the average number of peptides targeted had increased to 5 (range 0-11). Of the 56 optimal Gag CTL epitopes sequenced, 31 were wild-type in the infecting viruses, but only 11 of 31 elicited measurable CD8(+) T-cell responses. Conclusions. These data demonstrate that the majority of CD8(+) responses are not elicited during acute HIV infection despite the presence of the cognate epitope in the infecting strain. There is a need to define factors that influence lack of induction of effective immune responses and the parameters that dictate immunodominance in acute infection. C1 [Radebe, Mopo; Nair, Kriebashnie; Chonco, Fundisiwe; Bishop, Karen; Wright, Jaclyn K.; van der Stok, Mary; Mncube, Zenele; Altfeld, Marcus; Walker, Bruce D.; Ndung'u, Thumbi] Univ KwaZulu Natal, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, HIV Pathogenesis Programme, ZA-4001 Durban, South Africa. [Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Altfeld, Marcus; Walker, Bruce D.; Ndung'u, Thumbi] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA. [Altfeld, Marcus; Walker, Bruce D.; Ndung'u, Thumbi] Harvard Univ, Boston, MA 02115 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Ndung'u, T (reprint author), Univ KwaZulu Natal, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, HIV Pathogenesis Programme, Private Bag X7, ZA-4001 Durban, South Africa. EM ndungu@ukzn.ac.za OI Bishop, Karen/0000-0003-4935-7708; Ndung'u, Thumbi/0000-0003-2962-3992 FU National Institutes of Health [ROI-AI067073]; South African AIDS Vaccine Initiative; Bill and Melinda Gates Foundation; Mark and Lisa Schwartz Foundation; South African Research Chairs Initiative; National Research Foundation; Ragon Institute of Massachusetts General Hospital; Massachusetts Institute of Technology and Harvard University; National Institute of Allergy and Infectious Diseases [K23 AI 068458] FX The HPP Acute Infection Study is funded by the National Institutes of Health (grant ROI-AI067073), the South African AIDS Vaccine Initiative, and the Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation. Additional funding came from the Mark and Lisa Schwartz Foundation and the South African Research Chairs Initiative. M. R. and J. K. W. are funded by the National Research Foundation and the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University. I. V. B. is funded by the National Institute of Allergy and Infectious Diseases (grant K23 AI 068458). T. N. holds the South African Department of Science and Technology/National Research Foundation Research Chair in Systems Biology of HIV/AIDS. NR 50 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2011 VL 204 IS 5 BP 768 EP 776 DI 10.1093/infdis/jir394 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 809QB UT WOS:000294070700014 PM 21844303 ER PT J AU Blendea, D Heist, EK Danik, SB Barrett, C Ruskin, JN Mansour, M AF Blendea, Dan Heist, E. Kevin Danik, Stephan B. Barrett, Conor Ruskin, Jeremy N. Mansour, Moussa TI Analysis of the left atrial appendage morphology by intracardiac echocardiography in patients with atrial fibrillation SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE Left atrial appendage; Left atrial appendage geometry; Atrial fibrillation; Intracardiac echocardiography; Left atrial appendage occlusion devices ID TRANSESOPHAGEAL ECHOCARDIOGRAPHY; OCCLUSION DEVICES; STROKE; IMPLANTATION; PREVENTION; EXPERIENCE AB Detailed information regarding the structure and dimensions of the left atrial appendage (LAA) is required to guide implantation of LAA occlusion devices in patients with atrial fibrillation (AF). Currently, this procedure is guided by transesophageal echocardiography (TEE). The objective of this study was to evaluate the accuracy of intracardiac echocardiography (ICE) in assessing LAA dimensions. The LAA anatomy was analyzed in 21 consecutive patients (age 62 +/- 9 years, five women, six paroxysmal AF) who underwent catheter ablation for AF. All patients had pre-procedural scans (computed tomography (CT), N = 9; magnetic resonance imaging (MRI), N = 12) of the left atrium (LA). An 8-Fr phased-array ICE catheter was used to obtain images of the LAA. The LAA was visualized with the ICE probe placed sequentially in the right atrium (RA, N = 21 patients), in the coronary sinus (CS, N = 20 patients), and in the LA (N = 21 patients). ICE imaging from the LA showed a LAA ostium diameter of 24 +/- 4 mm and a LAA depth of 32 +/- 4 mm. There was strong correlation between the measurements by ICE and the values obtained by CT and MRI. The LAA was visualized in all cases from all locations (RA, CS, and LA), but complete visualization of the LAA could not be obtained from the RA and the CS in a significant number of cases, preventing accurate measurements. Imaging of LAA using an ICE probe positioned in the LA results in accurate measurements of LAA dimensions. This imaging modality could potentially be used during implantation of LAA occlusion devices as an alternative to TEE. C1 [Blendea, Dan; Heist, E. Kevin; Danik, Stephan B.; Barrett, Conor; Ruskin, Jeremy N.; Mansour, Moussa] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org FU Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; St. Jude Medical; Boston Scientific FX This work was partially supported by the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; Dr. Dan Blendea, Dr. Stephan Danik, and Dr. Conor Barrett have no potential conflicts of interest. Dr. E. Kevin Heist has served as a consultant and received research grants from St. Jude Medical and Boston Scientific. Dr. Jeremy N. Ruskin has served as consultant for Medtronic and Biosense Webster and received honorarium for faculty participation in Fellows program from Boston Scientific and St. Jude Medical. Dr. Moussa Mansour has served as a consultant for Biosense Webster. NR 11 TC 10 Z9 10 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD SEP PY 2011 VL 31 IS 3 BP 191 EP 196 DI 10.1007/s10840-011-9559-z PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 808IY UT WOS:000293972600002 PM 21455699 ER PT J AU Kavishwar, A Medarova, Z Moore, A AF Kavishwar, Amol Medarova, Zdravka Moore, Anna TI Unique sphingomyelin patches are targets of a beta-cell-specific antibody SO JOURNAL OF LIPID RESEARCH LA English DT Article DE beta cell marker; beta cell mass; beta cell imaging ID THIN-LAYER CHROMATOGRAPHY; DIABETES-MELLITUS; LIPID RAFTS; MEMBRANE; MASS; PHOSPHOLIPIDS; CERAMIDE; STRESS; MODEL; RAT AB To devise successful imaging and therapeutic strategies, the identification of beta-cell surface markers is one of the challenges in diabetes research that has to be resolved. We previously showed that IC2, a rat monoclonal IgM antibody, can be used for ex vivo determination of beta-cell mass by imaging. Further progress toward the development of an antibody-based imaging agent was hampered by the lack of knowledge regarding the nature and composition of the IC2 antigen. Here, we show a series of systematic experiments involving classical lipid extraction and chromatography techniques combined with immunochemistry, which led to the identification of sphingomyelin as the target antigen assembled in the form of patches on the beta-cell surface. Our findings were verified by modulating SM by enzymatic cleavage, downregulation, upregulation, and perturbation of membrane SM and observation of corresponding changes in IC2 binding. Cholesterol participates in stabilization of these patches, as its removal results in loss of IC2 binding. We believe that these findings have implications for identifying future ligands for the proposed antigen for imaging purposes as well as for potential therapy, as sphingomyelin has been shown to play a role in the apoptotic cascade in pancreatic beta cells.-Kavishwar, A., Z. Medarova, and A. Moore. Unique sphingomyelin patches are targets of a beta-cell-specific antibody. J. Lipid Res. 2011. 52: 1660-1671. C1 [Kavishwar, Amol; Medarova, Zdravka; Moore, Anna] Harvard Univ, Sch Med, Dept Radiol,MGH,MIT,Mol Imaging Lab, Massachusetts Gen Hosp,HMS Athinoula A Martinous, Boston, MA 02115 USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Dept Radiol,MGH,MIT,Mol Imaging Lab, Massachusetts Gen Hosp,HMS Athinoula A Martinous, Boston, MA 02115 USA. EM amoore@helix.mgh.harvard.edu OI Kavishwar, Amol/0000-0001-8214-6625 FU Juvenile Diabetes Research Foundation [JDRF 37-2009-30] FX This work was supported in part by Juvenile Diabetes Research Foundation Award JDRF 37-2009-30 (A. M.). NR 38 TC 6 Z9 7 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2011 VL 52 IS 9 BP 1660 EP 1671 DI 10.1194/jlr.M017582 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 806RL UT WOS:000293827600006 PM 21747097 ER PT J AU McDonald, CC Wiebe, DJ Guerra, T Thomas, N Richmond, TS AF McDonald, C. C. Wiebe, D. J. Guerra, T. Thomas, N. Richmond, T. S. TI The importance of family to youth living in violent communities SO JOURNAL OF PSYCHIATRIC AND MENTAL HEALTH NURSING LA English DT Article ID EXPOSURE C1 [McDonald, C. C.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia Collaborat Violence Prevent Ctr, Philadelphia, PA 19104 USA. [Wiebe, D. J.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia Collaborat Violence Prevent Ctr, Philadelphia, PA 19104 USA. [Richmond, T. S.] Univ Penn, Sch Nursing, Dept Biobehav & Hlth Sci, Philadelphia Collaborat Violence Prevent Ctr, Philadelphia, PA 19104 USA. RP McDonald, CC (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Philadelphia Collaborat Violence Prevent Ctr, Philadelphia, PA 19104 USA. FU Centers for Disease Control and Prevention [5 U49 CE001093]; National Institute of Nursing Research [F31NR011107] FX This manuscript was supported by the cooperative agreement number 5 U49 CE001093 from The Centers for Disease Control and Prevention. Its contents are the sole responsibility of the authors and do not represent the official position of the Centers for Disease Control and Prevention. This research was also supported by Award Number F31NR011107 (PI: Catherine C. McDonald) from the National Institute of Nursing Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. NR 10 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-0126 J9 J PSYCHIATR MENT HLT JI J. Psychiatr. Ment. Health Nurs. PD SEP PY 2011 VL 18 IS 7 BP 653 EP 656 DI 10.1111/j.1365-2850.2011.01774.x PG 4 WC Nursing; Psychiatry SC Nursing; Psychiatry GA 808WG UT WOS:000294011900014 PM 21848601 ER PT J AU Haines, J Ziyadeh, NJ Franko, DL McDonald, J Mond, JM Austin, SB AF Haines, Jess Ziyadeh, Najat J. Franko, Debra L. McDonald, Julia Mond, Jonathan M. Austin, S. Bryn TI Screening High School Students for Eating Disorders: Validity of Brief Behavioral and Attitudinal Measures SO JOURNAL OF SCHOOL HEALTH LA English DT Article DE screening; eating disorders; high school students ID ADOLESCENT GIRLS; TREATMENT-SEEKING; SELF-REPORT; QUESTIONNAIRE; INTERVIEW; SYMPTOMS; PATTERNS; NERVOSA; BULIMIA; ONSET AB BACKGROUND: Early identification can greatly impact the trajectory of eating disorders, and school-based screening is 1 avenue for identifying those at risk. To be feasible in a school setting, a screening program must use a brief, valid screening tool. The aim of this study was to assess how well brief attitudinal and behavioral survey items identify adolescents at risk in a large sample of high school students from across the United States. METHODS: Data were drawn from the National Eating Disorder Screening Program, the first-ever national eating disorders screening initiative for US high schools. A 2-stage, clustered sampling method was used to randomly select a subset of student screening forms (n = 5740), which included the Eating Attitudes Test (EAT-26), behavioral questions assessing the frequency of vomiting and binge eating in the past 3 months, and an attitudinal item that assessed preoccupation with thinness. RESULTS: Nearly 12% of females and 3% of males reported vomiting to control their weight and 17% of females and 10% of males reported binge eating 1 or more times per month. Approximately 24% of females and 8% of males report being preoccupied with being thinner. We found that the attitudinal measure yielded high sensitivity and specificity. Combined screening measures that used both the attitudinal and behavioral items yielded slightly higher sensitivity values than those found with the attitudinal measure alone. CONCLUSION: High school administrators should include items that assess both preoccupation with thinness as well as behavioral items that deal with eating disorders on student health surveys. C1 [Haines, Jess] Univ Guelph, Dept Family Relat & Appl Nutr, Guelph, ON N1G 2W1, Canada. [Ziyadeh, Najat J.] Childrens Hosp, Div Adolescent & Young Adult Med, Dept Med, Boston, MA 02115 USA. [Ziyadeh, Najat J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Franko, Debra L.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Sch Hlth Profess, Boston, MA 02115 USA. [Franko, Debra L.] Massachusetts Gen Hosp, Harris Ctr Educ & Advocacy Eating Disorders, Boston, MA 02114 USA. [McDonald, Julia] Harvard Univ, Med Sch Harvard Pilgrim Hlth Care, Obes Prevent Program, Dept Populat Med, Boston, MA 02215 USA. [Mond, Jonathan M.] Univ Western Sydney, Sch Biomed & Hlth Sci, Penrith, NSW 1797, Australia. [Austin, S. Bryn] Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA. [Austin, S. Bryn] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Haines, J (reprint author), Univ Guelph, Dept Family Relat & Appl Nutr, Room 226,Macdonald Stewart Hall,50 Stone Rd E, Guelph, ON N1G 2W1, Canada. EM jhaines@uoguelph.ca; Najat.Ziyadeh@i3drugsafety.com; d.franko@neu.edu; Julia_McDonald@hphc.org; J.Mond@uws.edu.au; bryn.austin@childrens.harvard.edu NR 25 TC 10 Z9 12 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD SEP PY 2011 VL 81 IS 9 BP 530 EP 535 DI 10.1111/j.1746-1561.2011.00623.x PG 6 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 806FB UT WOS:000293790600003 PM 21831065 ER PT J AU Zeitlin, SI AF Zeitlin, Scott I. TI Is Prostatitis a Vascular Disease? SO JOURNAL OF UROLOGY LA English DT Editorial Material ID PELVIC PAIN SYNDROME; MEN C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Zeitlin, SI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2011 VL 186 IS 3 BP 781 EP 782 DI 10.1016/j.juro.2011.06.011 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 804XL UT WOS:000293688300003 PM 21788041 ER PT J AU Chang, P Szymanski, KM Dunn, RL Chipman, JJ Litwin, MS Nguyen, PL Sweeney, CJ Cook, R Wagner, AA DeWolf, WC Bubley, GJ Funches, R Aronovitz, JA Wei, JT Sanda, MG AF Chang, Peter Szymanski, Konrad M. Dunn, Rodney L. Chipman, Jonathan J. Litwin, Mark S. Nguyen, Paul L. Sweeney, Christopher J. Cook, Robert Wagner, Andrew A. DeWolf, William C. Bubley, Glenn J. Funches, Renee Aronovitz, Joseph A. Wei, John T. Sanda, Martin G. TI Expanded Prostate Cancer Index Composite for Clinical Practice: Development and Validation of a Practical Health Related Quality of Life Instrument for Use in the Routine Clinical Care of Patients With Prostate Cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; quality of life; outcome assessment (health care); questionnaires ID RADICAL PROSTATECTOMY; SEXUAL FUNCTION; MEN; RADIOTHERAPY; HYPERPLASIA; OUTCOMES; FINASTERIDE; THERAPY; URINARY; BICALUTAMIDE AB Purpose: Measuring the health related quality of life of patients with prostate cancer in routine clinical practice is hindered by the lack of instruments enabling efficient, real-time, point of care scoring of multiple health related quality of life domains. Thus, we developed an instrument for this purpose. Materials and Methods: The Expanded Prostate Cancer Index Composite for Clinical Practice is a 1-page, 16-item questionnaire that we constructed to measure urinary incontinence, urinary irritation, and the bowel, sexual and hormonal health related quality of life domains. We eliminated conceptually overlapping items from the 3-page Expanded Prostate Cancer Index Composite-26 and revised the questionnaire format to mirror the AUA symptom index, thereby enabling practitioners to calculate health related quality of life scores at the point of care. We administered the Expanded Prostate Cancer Index Composite for Clinical Practice to a new cohort of patients with prostate cancer in community based and academic oncology, radiation, and urology practices to evaluate instrument validity as well as ease of use in clinical practice. Results: A total of 175 treated and 132 untreated subjects with prostate cancer completed the Expanded Prostate Cancer Index Composite for Clinical Practice. The domain scores of the Expanded Prostate Cancer Index Composite for Clinical Practice correlated highly with the respective domain scores from longer versions of the Expanded Prostate Cancer Index Composite (r >= 0.93 for all domains). The Expanded Prostate Cancer Index Composite for Clinical Practice showed high internal consistency (Cronbach's alpha 0.64-0.84) and sensitivity to prostate cancer treatment related effects (p < 0.05 in each of 5 health related quality of life domains). Patients completed the Expanded Prostate Cancer Index Composite for Clinical Practice efficiently (96% in less than 10 minutes and with 11% missing items). It was deemed very convenient by clinicians in 87% of routine clinical encounters and clinicians accurately scored completed questionnaires 94% of the time. Conclusions: The Expanded Prostate Cancer Index Composite for Clinical Practice is a valid instrument that enables patient reported, health related quality of life to be measured efficiently and accurately at the point of care, and thereby facilitates improved emphasis and management of patient reported outcomes. C1 [Chang, Peter; Wagner, Andrew A.; DeWolf, William C.; Sanda, Martin G.] Beth Israel Deaconess Med Ctr, Div Urol, Dept Surg, Boston, MA 02215 USA. [Bubley, Glenn J.; Funches, Renee] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Aronovitz, Joseph A.] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Chang, Peter] Brigham & Womens Hosp, Dept Surg, Div Urol, Boston, MA 02115 USA. [Nguyen, Paul L.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Chipman, Jonathan J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Sweeney, Christopher J.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Wagner, Andrew A.; DeWolf, William C.; Bubley, Glenn J.; Sanda, Martin G.] Harvard Univ, Sch Med, Boston, MA USA. [Szymanski, Konrad M.; Wei, John T.] McGill Univ, Ctr Hlth, Div Urol, Montreal, PQ, Canada. [Dunn, Rodney L.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA. [Litwin, Mark S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Cook, Robert] Centra Hlth, Hills Urol 7, Lynchburg, VA USA. RP Sanda, MG (reprint author), Beth Israel Deaconess Med Ctr, Div Urol, Dept Surg, 330 Brookline Ave,Rabb 440, Boston, MA 02215 USA. EM msanda@bidmc.harvard.edu RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; Wei, John/E-8967-2012 FU National Institutes of Health [R01 CA95662, RC1 CA146596] FX Supported by the National Institutes of Health (R01 CA95662, RC1 CA146596). NR 27 TC 39 Z9 39 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2011 VL 186 IS 3 BP 865 EP 872 DI 10.1016/j.juro.2011.04.085 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 804XL UT WOS:000293688300030 PM 21788038 ER PT J AU D'Amico, AV Chen, MH Dosoretz, D Katin, M Salenius, S Ross, R Goldhaber, SZ AF D'Amico, Anthony V. Chen, Ming-Hui Dosoretz, Daniel Katin, Michael Salenius, Sharon Ross, Rudi Goldhaber, Samuel Z. TI Coronary Artery Revascularization and the Risk of Death in Men With Prostate Cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; watchful waiting; cardiovascular diseases; mortality ID ACTIVE SURVEILLANCE; HEART-FAILURE; TASK-FORCE; APPROPRIATENESS; MORTALITY; CRITERIA; SOCIETY; SURGERY AB Purpose: We investigated whether the decrease in death from cardiovascular disease, a major competing risk, explains the observed increase in prostate cancer specific mortality before 1992. Materials and Methods: Between 1991 and 2006, 1,880 men with known cardiovascular disease underwent radiation therapy for prostate cancer and were followed until July 2008. Cox regression multivariable analysis was performed to assess whether known prostate cancer prognostic factors, history of coronary artery revascularization for cardiovascular disease, age, Charlson comorbidity score and prostate cancer treatment were associated with the risk of death. Results: Despite a significantly higher Charlson comorbidity score (p < 0.001) due to a higher rate of prior myocardial infarction, the risk of death was significantly lower (adjusted hazard ratio 0.63, 95% CI 0.49-0.82, p < 0.001) in men who underwent revascularization. High grade prostate cancer contributed significantly to the risk of death in men who underwent revascularization (AHR 1.74, 95% CI 1.04-2.91, p = 0.04) but not in those who did not (AHR 1.18, 95% CI 0.88-1.58, p = 0.27). Conclusions: The availability of and appropriate selection for revascularization may explain the increase in prostate cancer specific mortality before 1992. Men with cardiovascular disease in whom revascularization was not appropriate could consider active surveillance of prostate cancer because the increased risk of death was not associated with high grade prostate cancer. C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goldhaber, Samuel Z.] Harvard Univ, Brigham & Womens Hosp, Dept Med & Cardiovasc Div, Sch Med, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Dosoretz, Daniel; Katin, Michael; Salenius, Sharon; Ross, Rudi] 21st Century Oncol, Ft Myers, FL USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L 2 Level, Boston, MA 02115 USA. EM adamico@partners.org NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2011 VL 186 IS 3 BP 898 EP 902 DI 10.1016/j.juro.2011.04.076 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 804XL UT WOS:000293688300037 PM 21788044 ER PT J AU Wilen, CB Parrish, NF Pfaff, JM Decker, JM Henning, EA Haim, H Petersen, JE Wojcechowskyj, JA Sodroski, J Haynes, BF Montefiori, DC Tilton, JC Shaw, GM Hahn, BH Doms, RW AF Wilen, Craig B. Parrish, Nicholas F. Pfaff, Jennifer M. Decker, Julie M. Henning, Elizabeth A. Haim, Hillel Petersen, Josiah E. Wojcechowskyj, Jason A. Sodroski, Joseph Haynes, Barton F. Montefiori, David C. Tilton, John C. Shaw, George M. Hahn, Beatrice H. Doms, Robert W. TI Phenotypic and Immunologic Comparison of Clade B Transmitted/Founder and Chronic HIV-1 Envelope Glycoproteins SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; HUMAN MONOCLONAL-ANTIBODIES; CCR5 DELTA 32; HETEROSEXUAL TRANSMISSION; PRIMARY INFECTION; TYPE-1 INFECTION; NEUTRALIZING ANTIBODIES; BIOLOGICAL PHENOTYPE; SEXUAL TRANSMISSION AB Sexual transmission of human immunodeficiency virus type 1 (HIV-1) across mucosal barriers is responsible for the vast majority of new infections. This relatively inefficient process results in the transmission of a single transmitted/founder (T/F) virus, from a diverse viral swarm in the donor, in approximately 80% of cases. Here we compared the biological activities of 24 clade B T/F envelopes (Envs) with those from 17 chronic controls to determine whether the genetic bottleneck that occurs during transmission is linked to a particular Env phenotype. To maximize the likelihood of an intact mucosal barrier in the recipients and to enhance the sensitivity of detecting phenotypic differences, only T/F Envs from individuals infected with a single T/F variant were selected. Using pseudotyping to assess Env function in single-round infectivity assays, we compared coreceptor tropism, CCR5 utilization efficiencies, primary CD4(+) T cell subset tropism, dendritic cell trans-infections, fusion kinetics, and neutralization sensitivities. T/F and chronic Envs were phenotypically equivalent in most assays; however, T/F Envs were modestly more sensitive to CD4 binding site antibodies b12 and VRC01, as well as pooled human HIV Ig. This finding was independently validated with a panel of 14 additional chronic HIV-1 Env controls. Moreover, the enhanced neutralization sensitivity was associated with more efficient binding of b12 and VRC01 to T/F Env trimers. These data suggest that there are subtle but significant structural differences between T/F and chronic clade B Envs that may have implications for HIV-1 transmission and the design of effective vaccines. C1 [Wilen, Craig B.; Pfaff, Jennifer M.; Henning, Elizabeth A.; Petersen, Josiah E.; Wojcechowskyj, Jason A.; Doms, Robert W.] Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Parrish, Nicholas F.; Decker, Julie M.; Shaw, George M.; Hahn, Beatrice H.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Parrish, Nicholas F.; Decker, Julie M.; Shaw, George M.; Hahn, Beatrice H.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Haim, Hillel; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Haynes, Barton F.; Montefiori, David C.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Tilton, John C.] Case Western Reserve Univ, Sch Med, Ctr Prote, Dept Gen Med Sci, Cleveland, OH 44106 USA. RP Doms, RW (reprint author), Johnson Pavil 225A,3610 Hamilton Walk, Philadelphia, PA 19104 USA. EM bhahn@uab.edu; doms@upenn.edu OI Parrish, Nicholas/0000-0002-6971-8016; Wilen, Craig/0000-0003-2495-9403 FU Center for HIV/AIDS Vaccine Immunology, National Institutes of Health [AI67854, AI27767, AI40880]; Bill and Melinda Gates Foundation [37874, 38619]; International AIDS Vaccine Initiative; [T32 AI000632]; [T32 GM008361] FX This work was funded by the Center for HIV/AIDS Vaccine Immunology, National Institutes of Health grants (AI67854, AI27767, and AI40880), the Bill and Melinda Gates Foundation grants 37874 and 38619, and the International AIDS Vaccine Initiative. C. B. W. and N.F.P. were supported by grants T32 AI000632 and T32 GM008361, respectively. NR 79 TC 68 Z9 69 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2011 VL 85 IS 17 BP 8514 EP 8527 DI 10.1128/JVI.00736-11 PG 14 WC Virology SC Virology GA 804AO UT WOS:000293626100006 PM 21715507 ER PT J AU Tang, HL Robinson, JE Gnanakaran, S Li, M Rosenberg, ES Perez, LG Haynes, BF Liao, HX LaBranche, CC Korber, BT Montefiori, DC AF Tang, Haili Robinson, James E. Gnanakaran, S. Li, Ming Rosenberg, Eric S. Perez, Lautaro G. Haynes, Barton F. Liao, Hua-Xin LaBranche, Celia C. Korber, Bette T. Montefiori, David C. TI Epitopes Immediately below the Base of the V3 Loop of gp120 as Targets for the Initial Autologous Neutralizing Antibody Response in Two HIV-1 Subtype B-Infected Individuals SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN; TYPE-1 INFECTION; C INFECTION; CLADE-C; MOLECULAR-DYNAMICS; RECEPTOR-BINDING; RHESUS MACAQUES; VIREMIA CONTROL AB Epitopes that drive the initial autologous neutralizing antibody response in HIV-1-infected individuals could provide insights for vaccine design. Although highly strain specific, these epitopes are immunogenic, vulnerable to antibody attack on infectious virus, and could be involved in the ontogeny of broadly neutralizing antibody responses. To delineate such epitopes, we used site-directed mutagenesis, autologous plasma samples, and autologous monoclonal antibodies to map the amino acid changes that led to escape from the initial autologous neutralizing antibody response in two HIV-1 subtype B-infected individuals. Additional mapping of the epitopes was accomplished by using alanine scanning mutagenesis. Escape in the two individuals occurred by different pathways, but the responses in both cases appeared to be directed against the same region of gp120. In total, three amino acid positions were identified that were independently associated with autologous neutralization. Positions 295 and 332 are located immediately before and after the N- and C-terminal cysteines of the V3 loop, respectively, the latter of which affected an N-linked glycan that was critical to the neutralization epitope. Position 415 affected an N-linked glycan at position 413 in the C terminus of V4 that might mask epitopes near the base of V3. All three sites lie in close proximity on a four-stranded antiparallel sheet on the outer domain of gp120. We conclude that a region just below the base of the V3 loop, near the coreceptor binding domain of gp120, can be a target for autologous neutralization. C1 [Tang, Haili; Li, Ming; Perez, Lautaro G.; LaBranche, Celia C.; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Haynes, Barton F.; Liao, Hua-Xin] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70118 USA. [Gnanakaran, S.; Korber, Bette T.] Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM USA. [Rosenberg, Eric S.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Rosenberg, Eric S.] Harvard Univ, Sch Med, Boston, MA USA. RP Montefiori, DC (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2926, Durham, NC 27710 USA. EM monte@duke.edu OI Gnanakaran, S/0000-0002-9368-3044; Korber, Bette/0000-0002-2026-5757 FU National Institutes of Health, National Institutes of Allergy and Infectious Diseases, Division of AIDS, Center for HIV/AIDS Vaccine Immunology (CHAVI) [AI0678501] FX This work was funded by the National Institutes of Health, National Institutes of Allergy and Infectious Diseases, Division of AIDS, Center for HIV/AIDS Vaccine Immunology (CHAVI), grant AI0678501. NR 107 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2011 VL 85 IS 18 BP 9286 EP 9299 DI 10.1128/JVI.02286-10 PG 14 WC Virology SC Virology GA 808DM UT WOS:000293956400004 PM 21734041 ER PT J AU Berger, CT Frahm, N Price, DA Mothe, B Ghebremichael, M Hartman, KL Henry, LM Brenchley, JM Ruff, LE Venturi, V Pereyra, F Sidney, J Sette, A Douek, DC Walker, BD Kaufmann, DE Brander, C AF Berger, Christoph T. Frahm, Nicole Price, David A. Mothe, Beatriz Ghebremichael, Musie Hartman, Kari L. Henry, Leah M. Brenchley, Jason M. Ruff, Laura E. Venturi, Vanessa Pereyra, Florencia Sidney, John Sette, Alessandro Douek, Daniel C. Walker, Bruce D. Kaufmann, Daniel E. Brander, Christian TI High-Functional-Avidity Cytotoxic T Lymphocyte Responses to HLA-B-Restricted Gag-Derived Epitopes Associated with Relative HIV Control SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HEPATITIS-C VIRUS; CELL RESPONSES; INFECTED-CELLS; VIRAL LOAD; SELECTION PRESSURE; CONSERVED REGIONS; CROSS-RECOGNITION; PERIPHERAL-BLOOD AB Virus-specific cytotoxic T lymphocytes (CTL) with high levels of functional avidity have been associated with viral clearance in hepatitis C virus infection and with enhanced antiviral protective immunity in animal models. However, the role of functional avidity as a determinant of HIV-specific CTL efficacy remains to be assessed. Here we measured the functional avidities of HIV-specific CTL responses targeting 20 different, optimally defined CTL epitopes restricted by 13 different HLA class I alleles in a cohort comprising 44 HIV controllers and 68 HIV noncontrollers. Responses restricted by HLA-B alleles and responses targeting epitopes located in HIV Gag exhibited significantly higher functional avidities than responses restricted by HLA-A or HLA-C molecules (P = 0.0003) or responses targeting epitopes outside Gag (P < 0.0001). The functional avidities of Gag-specific and HLA-B-restricted responses were higher in HIV controllers than in noncontrollers (P = 0.014 and P = 0.018) and were not restored in HIV noncontrollers initiating antiretroviral therapy. T-cell receptor (TCR) analyses revealed narrower TCR repertoires in higher-avidity CTL populations, which were dominated by public TCR sequences in HIV controllers. Together, these data link the presence of high-avidity Gag-specific and HLA-B-restricted CTL responses with viral suppression in vivo and provide new insights into the immune parameters that mediate spontaneous control of HIV infection. C1 [Berger, Christoph T.; Ghebremichael, Musie; Hartman, Kari L.; Henry, Leah M.; Pereyra, Florencia; Walker, Bruce D.; Kaufmann, Daniel E.; Brander, Christian] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Berger, Christoph T.; Ghebremichael, Musie; Hartman, Kari L.; Henry, Leah M.; Pereyra, Florencia; Walker, Bruce D.; Kaufmann, Daniel E.; Brander, Christian] Harvard Univ, Boston, MA 02115 USA. [Frahm, Nicole] Fred Hutchinson Canc Res Ctr, NIAID HIV Vaccine Trials Network HVTN, Seattle, WA 98104 USA. [Price, David A.; Brenchley, Jason M.; Ruff, Laura E.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales. [Mothe, Beatriz] Univ Autonoma Badalona, Hosp Germans Trias & Pujol, Lluita Sida Fdn, Barcelona, Spain. [Mothe, Beatriz; Brander, Christian] Hosp Badalona Germans Trias & Pujol, IrsiCaixa AIDS Res Inst HIVACAT, Barcelona, Spain. [Ghebremichael, Musie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Venturi, Vanessa] Univ New S Wales, Ctr Vasc Res, Computat Biol Grp, Kensington, NSW 2033, Australia. [Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Brander, Christian] ICREA, Barcelona, Spain. RP Brander, C (reprint author), Hosp Badalona Germans Trias & Pujol, Fdn IrsiCaixa HIVACAT, AIDS Res Inst, Ctra Canyet S-N, Barcelona 08916, Catalonia, Spain. EM cbrander@irsicaixa.es RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Brander, Christian/0000-0002-0548-5778 FU National Institutes of Health [R01 067 077]; Spanish FIPSE [36-0737-09]; University of Basel, Basel, Switzerland; Janggen-Pohn Foundation, Switzerland; FIS, Madrid, Spain [CM08/00020] FX This work was funded by a National Institutes of Health grant to C. B. and D. E. K. (R01 067 077) and in part by the Spanish FIPSE grant 36-0737-09. C. T. B. is supported by a research grant from the University of Basel, Basel, Switzerland, and the Janggen-Pohn Foundation, Switzerland. D. A. P. is a Medical Research Council (United Kingdom) senior clinical fellow. B. M. holds a research fellowship grant from the FIS (Rio Hortega; CM08/00020), Madrid, Spain. C. B. is a senior ICREA research professor. NR 87 TC 64 Z9 65 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2011 VL 85 IS 18 BP 9334 EP 9345 DI 10.1128/JVI.00460-11 PG 12 WC Virology SC Virology GA 808DM UT WOS:000293956400008 PM 21752903 ER PT J AU Buzon, MJ Seiss, K Weiss, R Brass, AL Rosenberg, ES Pereyra, F Yu, XG Lichterfeld, M AF Buzon, Maria J. Seiss, Katherine Weiss, Robert Brass, Abraham L. Rosenberg, Eric S. Pereyra, Florencia Yu, Xu G. Lichterfeld, Mathias TI Inhibition of HIV-1 Integration in Ex Vivo-Infected CD4 T Cells from Elite Controllers SO JOURNAL OF VIROLOGY LA English DT Article ID DETERMINANTS AB Elite controllers spontaneously maintain undetectable levels of HIV-1 replication for reasons that remain unclear. Here, we show that in elite controllers, direct ex vivo infection of purified CD4 T cells without prior in vitro activation results in disproportionately low levels of integrated HIV-1 DNA relative to the quantity of reverse transcripts, while the levels of two-long terminal repeat (2-LTR) circles were excessively elevated relative to those of integrated HIV-1 DNA. This indicates that chromosomal HIV-1 integration is inhibited in ex vivo-infected CD4 T cells from elite controllers. This defect in HIV-1 integration was unrelated to p21, a host protein that can restrict early HIV-1 replication steps, and was not visible following infection of in vitro-activated CD4 T cells from elite controllers. These data contribute to increasing evidence that intrinsic inhibition of specific HIV-1 replication steps plays an important role in the ability of elite controllers to maintain undetectable viral loads. C1 [Buzon, Maria J.; Rosenberg, Eric S.; Lichterfeld, Mathias] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Buzon, Maria J.; Seiss, Katherine; Brass, Abraham L.; Pereyra, Florencia; Yu, Xu G.] Ragon Inst, Boston, MA USA. [Weiss, Robert] Univ Calif Davis, Div Nephrol, Davis, CA 95616 USA. [Pereyra, Florencia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Lichterfeld, M (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM mlichterfeld@partners.org RI Buzon, Maria J/G-8286-2015 OI Buzon, Maria J/0000-0003-4427-9413 FU U.S. National Institutes of Health [AI093203, AI078799, AI089339]; Doris Duke Clinical Scientist Development Award; European Molecular Biology Laboratory (EMBL); NIH [CA135401, DK082690]; Medical Service of the U.S. Department of Veterans Affairs FX This work was supported by the U.S. National Institutes of Health (AI093203 to M. L. and AI078799 and AI089339 to X.G.Y.). M. L. and X.G.Y. are both recipients of the Doris Duke Clinical Scientist Development Award. M.J.B. is supported by a Fellowship Award from the European Molecular Biology Laboratory (EMBL). R. W. is supported by the NIH (grants CA135401 and DK082690) and by the Medical Service of the U.S. Department of Veterans Affairs. NR 16 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2011 VL 85 IS 18 BP 9646 EP 9650 DI 10.1128/JVI.05327-11 PG 5 WC Virology SC Virology GA 808DM UT WOS:000293956400038 PM 21734042 ER PT J AU Chen, JL Hartono, JR John, R Bennett, M Zhou, XJ Wang, YX Wu, QQ Winterberg, PD Nagami, GT Lu, CY AF Chen, Jianlin Hartono, John R. John, Reji Bennett, Michael Zhou, Xin Jin Wang, Yanxia Wu, Qingqing Winterberg, Pamela D. Nagami, Glenn T. Lu, Christopher Y. TI Early interleukin 6 production by leukocytes during ischemic acute kidney injury is regulated by TLR4 SO KIDNEY INTERNATIONAL LA English DT Article DE acute kidney injury; acute renal failure; inflammation; ischemia-reperfusion; ischemic renal failure ID ACUTE-RENAL-FAILURE; TOLL-LIKE RECEPTOR-2; GROUP BOX-1 PROTEIN; REPERFUSION INJURY; INFLAMMATORY RESPONSE; C57BL/10SCCR MICE; IN-VIVO; ISCHEMIA/REPERFUSION INJURY; EPITHELIAL-CELLS; GENE-EXPRESSION AB Although leukocytes infiltrate the kidney during ischemic acute kidney injury (AKI) and release interleukin 6 (IL6), their mechanism of activation is unknown. Here, we tested whether Toll-like receptor 4 (TLR4) on leukocytes mediated this activation by interacting with high-mobility group protein B1 (HMGB1) released by renal cells as a consequence of ischemic kidney injury. We constructed radiation-induced bone marrow chimeras using C3H/HeJ and C57BL/10ScNJ strains of TLR4 (-/-) mice and their respective TLR4 (+/+) wild-type counterparts and studied them at 4 h after an ischemic insult. Leukocytes adopted from TLR4 (+/+) mice infiltrated the kidneys of TLR4 (-/-) mice, and TLR4 (-/-) leukocytes infiltrated the kidneys of TLR4 (+/+) mice but caused little functional renal impairment in each case. Maximal ischemic AKI required both radiosensitive leukocytes and radioresistant renal parenchymal and endothelial cells from TLR4 (+/+) mice. Only TLR4 (+/+) leukocytes produced IL6 in vivo and in response to HMGB1 in vitro. Thus, following infiltration of the injured kidney, leukocytes produce IL6 when their TLR4 receptors interact with HMGB1 released by injured renal cells. This underscores the importance of TLR4 in the pathogenesis of ischemic AKI. Kidney International (2011) 80, 504-515; doi:10.1038/ki.2011.140; published online 1 June 2011 C1 [Chen, Jianlin; Hartono, John R.; John, Reji; Wang, Yanxia; Wu, Qingqing; Lu, Christopher Y.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Nephrol, Dallas, TX 75390 USA. [Bennett, Michael; Zhou, Xin Jin] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Winterberg, Pamela D.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Lu, Christopher Y.] Univ Texas SW Med Ctr Dallas, Grad Program Immunol, Dallas, TX 75390 USA. [Nagami, Glenn T.] Vet Affairs Greater Los Angeles Healthcare Syst, Nephrol Sect, Med Serv, Los Angeles, CA USA. [Nagami, Glenn T.] Vet Affairs Greater Los Angeles Healthcare Syst, Nephrol Sect, Res Serv, Los Angeles, CA USA. RP Lu, CY (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Nephrol, Dallas, TX 75390 USA. EM christopher.lu@utsouthwestern.edu FU NIH [RO-1 DK069633, F32DK084701, T32DK07257]; Beecherl Foundation; NIH, UT Southwesterrn O'Brien Kidney Research Core Center [DK079328] FX This study was supported by NIH RO-1 DK069633 and a Beecherl Foundation Grant to CYL; NIH F32DK084701 and T32DK07257 to JRH; and the NIH DK079328 UT Southwesterrn O'Brien Kidney Research Core Center. We thank Thomas Carroll for the low-power photography and Kathy Trueman for assistance in preparing the manuscript and figures. NR 86 TC 27 Z9 31 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2011 VL 80 IS 5 BP 504 EP 515 DI 10.1038/ki.2011.140 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 806UX UT WOS:000293840800012 PM 21633411 ER PT J AU Leon, A Staropoli, JF Hernandez, JM Longtine, JA Kuo, FC Dal Cin, P AF Leon, Annette Staropoli, John F. Hernandez, Jesus M. Longtine, Janina A. Kuo, Frank C. Dal Cin, Paola TI Translocation t(1;9) is a recurrent cytogenetic abnormality associated with progression of essential thrombocythemia patients displaying the JAK2 V617F mutation SO LEUKEMIA RESEARCH LA English DT Article DE Translocation; Essential thrombocythemia; JAK2; Myeloproliferative neoplasm; Derivative chromosome ID CHRONIC MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA RUBRA VERA; PROGNOSTIC-SIGNIFICANCE; TRISOMY 1Q; MYELOFIBROSIS; CHROMOSOME; 9P; MALIGNANCIES; PHENOTYPE; KARYOTYPE AB A cohort of 338 patients diagnosed with myeloproliferative neoplasms was investigated by conventional cytogenetics and evaluated for the presence of the JAK2 V617F mutation. A t(1;9)(p10;q10) in addition to two extra der(1;9)(q10;p10) chromosomes was observed in two patients of essential thrombocythemia that transformed to acute myelogenous leukemia or to myelofibrosis. These findings suggest that the presence of extra derivative chromosomes der(1q;9p) in combination with the JAK2 V617F mutation may play a role in the progression of myeloproliferative neoplasms and supports the use of cytogenetics in the follow-up of the disease. Published by Elsevier Ltd. C1 [Leon, Annette] GenPath, BioReference Labs, Elmwood Pk, NJ USA. [Staropoli, John F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hernandez, Jesus M.] Univ Salamanca, Unidad Diagnost Mol & Celular Canc, IBMCC, Ctr Invest Canc,CSIC, E-37008 Salamanca, Spain. [Hernandez, Jesus M.] Hosp Univ Salamanca, Serv Hematol, Salamanca, Spain. [Longtine, Janina A.; Kuo, Frank C.; Dal Cin, Paola] Harvard Univ, Sch Med, Dept Pathol, Ctr Adv Mol Diagnost,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Leon, A (reprint author), GenPath, BioReference Labs, 481 Edward H Ross Dr, Elmwood Pk, NJ USA. EM ameredith@bioreference.com RI 2011, Secribsal/D-9425-2012; Hernandez-Rivas, Jesus Maria/B-5459-2017 OI Hernandez-Rivas, Jesus Maria/0000-0002-9661-9371 NR 36 TC 1 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD SEP PY 2011 VL 35 IS 9 BP 1188 EP 1192 DI 10.1016/j.leukres.2011.02.001 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 806BW UT WOS:000293778200029 PM 21376394 ER PT J AU Ratai, EM Annamalai, L Burdo, T Joo, CG Bombardier, JP Fell, R Hakimelahi, R He, JL Lentz, MR Campbell, J Curran, E Halpern, EF Masliah, E Westmoreland, SV Williams, KC Gonzalez, RG AF Ratai, Eva-Maria Annamalai, Lakshmanan Burdo, Tricia Joo, Chan-Gyu Bombardier, Jeffrey P. Fell, Robert Hakimelahi, Reza He, Julian Lentz, Margaret R. Campbell, Jennifer Curran, Elizabeth Halpern, Elkan F. Masliah, Eliezer Westmoreland, Susan V. Williams, Kenneth C. Gonzalez, R. Gilberto TI Brain Creatine Elevation and N-Acetylaspartate Reduction Indicates Neuronal Dysfunction in the Setting of Enhanced Glial Energy Metabolism in a Macaque Model of NeuroAIDS SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE HIV; SIV; macaques; MR spectroscopy; creatine; gliosis ID MAGNETIC-RESONANCE-SPECTROSCOPY; AIDS DEMENTIA COMPLEX; IMMUNODEFICIENCY-VIRUS-INFECTION; CENTRAL-NERVOUS-SYSTEM; NAIVE HIV PATIENTS; SIV INFECTION; ANTIRETROVIRAL THERAPY; MR SPECTROSCOPY; INJURY; REVEALS AB Proton magnetic resonance spectroscopy has emerged as one of the most informative neuroimaging modalities for studying the effect of HIV infection in the brain, providing surrogate markers by which to assess disease progression and monitor treatment. Reductions in the level of N-Acetylaspartate and N-Acetylaspartate/creatine are established markers of neuronal injury or loss. However, the biochemical basis of altered creatine levels in neuroAIDS is not well understood. This study used a rapid progression macaque model of neuroAIDS to elucidate the changes in creatine. As the disease progressed, proton magnetic resonance spectroscopy revealed a decrease in N-Acetylaspartate, indicative of neuronal injury, and an increase in creatine yet to be elucidated. Subsequently, immunohistochemistry and stereology measures of decreased synaptophysin, microtubule-associated protein 2, and neuronal density confirmed neuronal injury. Furthermore, increases in ionized calcium binding adaptor molecule 1 and ghat fibrillary acidic protein indicated microglial and astroglial activation, respectively. Given these data, elevated creatine may reflect enhanced high-energy phosphate turnover in highly metabolizing activated astrocytes and microglia. Magn Reson Med 66:625-634, 2011. (C)2011 Wiley-Liss, Inc. C1 [Ratai, Eva-Maria; Joo, Chan-Gyu; Bombardier, Jeffrey P.; Fell, Robert; Hakimelahi, Reza; He, Julian; Lentz, Margaret R.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Div, Charlestown, MA USA. [Ratai, Eva-Maria; Joo, Chan-Gyu; Bombardier, Jeffrey P.; Fell, Robert; Hakimelahi, Reza; He, Julian; Lentz, Margaret R.; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ratai, Eva-Maria; Annamalai, Lakshmanan; Joo, Chan-Gyu; Bombardier, Jeffrey P.; Fell, Robert; Hakimelahi, Reza; He, Julian; Lentz, Margaret R.; Curran, Elizabeth; Westmoreland, Susan V.; Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Boston, MA USA. [Annamalai, Lakshmanan; Curran, Elizabeth; Westmoreland, Susan V.] New England Primate Res Ctr, Div Comparat Pathol, Southborough, MA USA. [Burdo, Tricia; Campbell, Jennifer; Williams, Kenneth C.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. [Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA 02114 USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285, 55 Fruit St, Boston, MA 02114 USA. EM rggonzalez@partners.org RI ANNAMALAI, LAKSHMANAN/F-4220-2011 FU NIH [R21NS059331, R01NS050041, R01NS040237, R01NS37654, R01MH62962, HNRC MH59754, HNRC MH62512, NS051129]; NEPRC [RR00168]; National Center for Research Resources [P41RR14075]; NIH Nonhuman Primate Reagent Resource [R24 RR016001, N01 AI040101] FX Grant sponsor: NIH; Grant numbers: R21NS059331, R01NS050041, R01NS040237, R01NS37654, R01MH62962, HNRC MH59754, HNRC MH62512, NS051129; Grant sponsor: NEPRC; Grant number: RR00168; Grant sponsor: National Center for Research Resources; Grant number: P41RR14075We thank Drs. Joanne Morris and Elisabeth Moeller, Ms. Shannon Luboyeski and staff from the Center of Comparative Medicine at Massachusetts General Hospital, as well as Dr. Angela Carville from the New England Primate Research Center (NEPRC) for animal veterinary care. We also thank Michael O'Connell for pathology support for this study, Dr. Ronald Desrosier for providing us the inoculum, SIVmac251, Drs. Mike Piatak and Jeffrey Lifson for viral load analyses (SAIC Frederick, Inc.), and Dr. Keith Reimann for the depleting anti-CD8 (human recombinant, cM-807) antibodies. Reagents used in these studies were provided by the NIH Nonhuman Primate Reagent Resource (R24 RR016001, N01 AI040101). Finally, we thank Nichole Eusemann for editing this manuscript. This work was supported by NIH grants R21NS059331 (EMR), R01NS050041 (RGG), R01NS040237 (KW), R01NS37654 (KW), R01MH62962 (EM), HNRC MH59754 (EM), HNRC MH62512 (EM), NS051129 (MRL) and RR00168 (NEPRC Base Grant). NR 40 TC 20 Z9 20 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD SEP PY 2011 VL 66 IS 3 BP 625 EP 634 DI 10.1002/mrm.22821 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 808OJ UT WOS:000293988000003 PM 21381104 ER PT J AU Chang, A Chou, CL Teherani, A Hauer, KE AF Chang, Anna Chou, Calvin L. Teherani, Arianne Hauer, Karen E. TI Clinical skills-related learning goals of senior medical students after performance feedback SO MEDICAL EDUCATION LA English DT Article ID SELF-ASSESSMENT; REMEDIATION; EDUCATION; ACCURACY; MOTIVATION AB CONTEXT Lifelong learning is essential for doctors to maintain competence in clinical skills. With performance feedback, learners should be able to formulate specific and achievable learning goals in areas of need. OBJECTIVES We aimed to determine: (i) the type and specificity of medical student learning goals after a required clinical performance examination; (ii) differences in goal setting among low, average and high performers, and (iii) whether low performers articulate learning goals that are concordant with their learning needs. METHODS We conducted a single-site, multi-year, descriptive comparison study. Senior medical students were given performance benchmarks, individual feedback and guidelines on learning goals; each student was subsequently instructed to write two clinical skills learning goals. Investigators coded the learning goals for specificity, categorised the goals, and performed statistical analyses to determine their concordance with student performance level (low, average or high) in data gathering (history taking and physical examination) or communication skills. RESULTS All 208 students each wrote two learning goals and most (n = 200, 96%) wrote two specific learning goals. Nearly two-thirds of low performers in data gathering wrote at least one learning goal that referred to history taking or physical examination; one-third wrote learning goals pertaining to the organisation of the encounter. High performers in data gathering wrote significantly more patient education goals and significantly fewer history-taking goals than average or low performers. Only 50% of low performers in communication wrote learning goals related to communication skills. Low performers in communication were significantly more likely than average or high performers to identify learning goals related to improving performance in future examinations. CONCLUSIONS The provision of performance benchmarking, individual feedback and brief written guidelines helped most senior medical students in our study to write specific clinical skills learning goals. Many low-performing students did not write learning goals concordant with their areas of weakness. Future work might focus on enhancing low performers' continued learning in areas of performance deficits. C1 [Chang, Anna] Univ Calif San Francisco, Div Geriatr, Dept Med, Sch Med, San Francisco, CA 94121 USA. [Chang, Anna; Chou, Calvin L.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. RP Chang, A (reprint author), Univ Calif San Francisco, Div Geriatr, Dept Med, Sch Med, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM Anna.Chang2@va.gov NR 34 TC 10 Z9 11 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0308-0110 J9 MED EDUC JI Med. Educ. PD SEP PY 2011 VL 45 IS 9 BP 878 EP 885 DI 10.1111/j.1365-2923.2011.04015.x PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 808XF UT WOS:000294014600005 PM 21848715 ER PT J AU Deshane, J Zmijewski, JW Luther, R Gaggar, A Deshane, R Lai, JF Xu, X Spell, M Estell, K Weaver, CT Abraham, E Schwiebert, LM Chaplin, DD AF Deshane, J. Zmijewski, J. W. Luther, R. Gaggar, A. Deshane, R. Lai, J-F Xu, X. Spell, M. Estell, K. Weaver, C. T. Abraham, E. Schwiebert, L. M. Chaplin, D. D. TI Free radical-producing myeloid-derived regulatory cells: potent activators and suppressors of lung inflammation and airway hyperresponsiveness SO MUCOSAL IMMUNOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; TUMOR-BEARING MICE; T-CELLS; ALVEOLAR MACROPHAGES; REACTIVE OXYGEN; MURINE MODEL; MILD ASTHMA; ARGINASE-I; SUPEROXIDE; INHIBITION AB Levels of reactive free radicals are elevated in the airway during asthmatic exacerbations, but their roles in the pathophysiology of asthma remain unclear. We have identified subsets of myeloid-derived suppressor-like cells as key sources of nitric oxide and superoxide in the lungs of mice with evolving experimental allergic airway inflammation and established these cells as master regulators of the airway inflammatory response. The profiles of free radicals they produced depended on expression of inducible nitric oxide synthase (iNOS), arginase, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. These radicals controlled the pro-and anti-inflammatory potential of these cells, and also regulated the reciprocal pattern of their infiltration into the lung. The nitric oxide-producing cells were Ly-6C(+)Ly-6G(-) and they downmodulated T-cell activation, recruited T(reg) cells, and dramatically downregulated antigen-induced airway hyperresponsiveness. The superoxide-producing cells were Ly-6C(-)Ly-6G(+) and they expressed proinflammatory activities, exacerbating airway hyperresponsiveness in a superoxide-dependent fashion. A smaller population of Ly-6C(+)Ly-6G(+) cells also suppressed T-cell responses, but in an iNOS- and arginase-independent fashion. These regulatory myeloid cells represent important targets for asthma therapy. C1 [Deshane, J.; Luther, R.; Deshane, R.; Lai, J-F; Chaplin, D. D.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Deshane, J.; Zmijewski, J. W.; Gaggar, A.; Xu, X.; Spell, M.; Abraham, E.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Deshane, J.; Zmijewski, J. W.; Abraham, E.; Schwiebert, L. M.; Chaplin, D. D.] Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Gaggar, A.] Birmingham VA Med Ctr, Birmingham, AL USA. [Spell, M.] Univ Alabama, Ctr AIDS Res, Birmingham, AL 35294 USA. [Estell, K.; Schwiebert, L. M.] Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. [Weaver, C. T.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Chaplin, D. D.] Univ Alabama, Comprehens Arthrit Musculoskeletal & Autoimmun Ct, Birmingham, AL 35294 USA. RP Chaplin, DD (reprint author), Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. EM dchaplin@uab.edu OI Weaver, Casey/0000-0002-2180-1793; Chaplin, David/0000-0002-1354-3069 FU NIH [5T32HL007553, 5T32AI007051, 1F32HL095341, 5P01HL073907, 5R01HL075465, 5R01HL062221, 1R01GM087748, 2R01HL076206] FX We thank Meiqin Zeng for expert technical assistance and Kathy May for management of the animal colony used to support this work. We gratefully acknowledge Hubert Tse for providing p47m mice to carry out adoptive transfer experiments. We also acknowledge helpful comments from Jack Lancaster, Carlene Zindl, Kelly M. McNagny, and Jillian Wohler. Support for these studies was provided by the NIH grants 5T32HL007553 (J.D.), 5T32AI007051 (J.D.), 1F32HL095341 (J.D.), 5P01HL073907 (D.D.C.), 5R01HL075465 (L.M.S.), 5R01HL062221 (E.A.), 1R01GM087748 (E.A.), and 2R01HL076206 (E.A.). NR 54 TC 35 Z9 39 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2011 VL 4 IS 5 BP 503 EP 518 DI 10.1038/mi.2011.16 PG 16 WC Immunology SC Immunology GA 809HC UT WOS:000294041400004 PM 21471960 ER PT J AU Hershcovici, T Mashimo, H Fass, R AF Hershcovici, T. Mashimo, H. Fass, R. TI The lower esophageal sphincter SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Review DE gamma-aminobutyric acid B (GABA(B)) receptor agonists; gastroesophageal reflux disorder; lower esophageal sphincter; TLESR reducers; transient lower esophageal sphincter relaxation ID GASTROESOPHAGEAL-REFLUX DISEASE; MULTICHANNEL INTRALUMINAL IMPEDANCE; RADIOFREQUENCY ENERGY DELIVERY; GASTRIC DISTENSION; ESOPHAGOGASTRIC JUNCTION; AGONIST BACLOFEN; SENSORY NEURONS; ACID EXPOSURE; FLAP VALVE; GAS REFLUX AB The lower esophageal sphincters (LES) together with the crural diaphragm are the major antireflux barriers protecting the esophagus from reflux of gastric content. However, reflux of gastric contents into the esophagus is a normal phenomenon in healthy individuals occurring primarily during episodes of transient lower esophageal sphincter relaxation (TLESR), defined as LES relaxation in the absence of a swallow. Transient lower esophageal sphincter relaxation is also the dominant mechanism of pathologic reflux in gastroesophageal reflux disorder (GERD) patients. Frequency of TLESR does not differ significantly between healthy individuals and those with GERD, but TLESRs are more likely to be associated with acid reflux in GERD patients. Understanding the mechanisms responsible for elicitation of a TLESR, using recently introduced novel technology is an area of intense interest. Pharmacologic and non-pharmacologic manipulation of receptors involved in the control of TLESR has recently emerged as a potential target for GERD therapy. C1 [Hershcovici, T.; Fass, R.] Univ Arizona, Neuroenter Clin Res Grp, So Arizona VA Hlth Care Syst, Hlth Sci Ctr, Tucson, AZ 85723 USA. [Mashimo, H.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Ctr Swallowing & Motil Disorders, Boston, MA USA. RP Fass, R (reprint author), Univ Arizona, Neuroenter Clin Res Grp, So Arizona VA Hlth Care Syst, Hlth Sci Ctr, 3601 S 6th Ave,1-111-GI, Tucson, AZ 85723 USA. EM Ronnie.Fass@va.gov FU Takeda; Wyeth; AstraZeneca FX Ronnie Fass, research support from Takeda, Wyeth, and AstraZeneca. Consultant for XenoPort, Vecta, GSK, and Reckitt Benckiser; Tiberiu Hershcovici, None; Hiroshi Mashimo, None. NR 63 TC 33 Z9 34 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD SEP PY 2011 VL 23 IS 9 BP 819 EP 830 DI 10.1111/j.1365-2982.2011.01738.x PG 12 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 807RN UT WOS:000293917500007 PM 21711416 ER PT J AU Sundaram, M Rosenthal, DI Hodler, J AF Sundaram, Murali Rosenthal, Daniel I. Hodler, Juerg TI Skeletal Radiology turns 40 SO SKELETAL RADIOLOGY LA English DT Editorial Material C1 [Sundaram, Murali] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Rosenthal, Daniel I.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Hodler, Juerg] Univ Zurich Hosp, CH-8091 Zurich, Switzerland. RP Sundaram, M (reprint author), Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. EM sundarm@ccf.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD SEP PY 2011 VL 40 IS 9 BP 1131 EP 1131 DI 10.1007/s00256-011-1221-4 PG 1 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 808KG UT WOS:000293976000001 PM 21847743 ER PT J AU Rosenthal, DI AF Rosenthal, Daniel I. TI The future of MSK interventions SO SKELETAL RADIOLOGY LA English DT Editorial Material ID BONE MORPHOGENETIC PROTEIN-2; RADIOFREQUENCY ABLATION C1 Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Rosenthal, DI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM dirosenthal@partners.org NR 20 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD SEP PY 2011 VL 40 IS 9 BP 1133 EP 1136 DI 10.1007/s00256-011-1225-0 PG 4 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 808KG UT WOS:000293976000002 PM 21847744 ER PT J AU Springfield, D AF Springfield, Dempsey TI Surgery for MSK tumors: 1971-2011 SO SKELETAL RADIOLOGY LA English DT Article DE Musculoskeletal neoplasia; Surgical resection; Limb salvage surgery ID PROSTHETIC BONE-REPLACEMENT; EN-BLOC RESECTION; OSTEOGENIC-SARCOMA; CHEMOTHERAPY; EXTREMITY; GRAFTS; FEMUR AB Since 1971 surgical management of musculoskeletal tumors has changed dramatically. In 1971 less than one-fourth of patients with a malignant tumor had limb salvage surgery, the remainder having an amputation. Amputations were also sometimes done for recurrent benign tumors. Since then amputation has become unusual for malignant disease and is virtually never done for benign tumors. The changes have been made possible because of advances in anesthesiology, surgery, radiology, medical oncology, and radiation oncology. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Springfield, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dspringfield@partners.org NR 22 TC 2 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD SEP PY 2011 VL 40 IS 9 BP 1233 EP 1237 DI 10.1007/s00256-011-1250-z PG 5 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 808KG UT WOS:000293976000010 PM 21826612 ER PT J AU Radley, JJ Kabbaj, M Jacobson, L Heydendael, W Yehuda, R Herman, JP AF Radley, Jason J. Kabbaj, Mohamed Jacobson, Lauren Heydendael, Willem Yehuda, Rachel Herman, James P. TI Stress risk factors and stress-related pathology: Neuroplasticity, epigenetics and endophenotypes SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Review DE Antidepressants; post-traumatic stress disorder; depression; glucocorticoids; hippocampus; individual differences ID MEDIAL PREFRONTAL CORTEX; PITUITARY-ADRENOCORTICAL AXIS; NOVELTY-SEEKING BEHAVIOR; TRANSCRIPTIONAL COACTIVATORS P300; CORTICOTROPIN-RELEASING HORMONE; RECEPTOR GENE-EXPRESSION; MESSENGER-RNA LEVELS; MALE C57BL/6 MICE; MAJOR DEPRESSION; INDIVIDUAL-DIFFERENCES AB This paper highlights a symposium on stress risk factors and stress susceptibility, presented at the Neurobiology of Stress workshop in Boulder, CO, in June 2010. This symposium addressed factors linking stress plasticity and reactivity to stress pathology in animal models and in humans. Dr. J. Radley discussed studies demonstrating prefrontal cortical neuroplasticity and prefrontal control of hypothalamo-pituitary-adrenocortical axis function in rats, highlighting the emerging evidence of the critical role that this region plays in normal and pathological stress integration. Dr. M. Kabbaj summarized his studies of possible epigenetic mechanisms underlying behavioral differences in rat populations bred for differential stress reactivity. Dr. L. Jacobson described studies using a mouse model to explore the diverse actions of antidepressants in brain, suggesting mechanisms whereby antidepressants may be differentially effective in treating specific depression endophenotypes. Dr. R. Yehuda discussed the role of glucocorticoids in post-traumatic stress disorder (PTSD), indicating that low cortisol level may be a trait that predisposes the individual to development of the disorder. Furthermore, she presented evidence indicating that traumatic events can have transgenerational impact on cortisol reactivity and development of PTSD symptoms. Together, the symposium highlighted emerging themes regarding the role of brain reorganization, individual differences, and epigenetics in determining stress plasticity and pathology. C1 [Herman, James P.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45237 USA. [Radley, Jason J.] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Kabbaj, Mohamed] Florida State Univ, Dept Biomed Sci, Program Neurosci, Tallahassee, FL 32306 USA. [Jacobson, Lauren; Heydendael, Willem] Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA. [Yehuda, Rachel] James J Peters VA Med Ctr, Bronx, NY USA. [Yehuda, Rachel] Mt Sinai Sch Med, Bronx, NY USA. RP Herman, JP (reprint author), Univ Cincinnati, Dept Psychiat, Psychiat N,Bldg E,2nd Floor,2170 E Galbraith Rd, Cincinnati, OH 45237 USA. EM james.herman@uc.edu RI Kabbaj, Mohamed/M-9240-2016; Herman, James/D-4960-2015 OI Herman, James/0000-0003-3571-2406 FU NIH [R13MH090623, R01MH087583, R21MH081046, R21MH 083128, R01MH080394]; NARSAD; Anxiety Disorders Association of America; VISN3 MIRECC, DOD [W81XWH-06-2-0032]; NIH ARRA [RC1MH088101]; Lightfighter Trust FX The 2010 Neurobiology of Stress Workshop was supported by NIH grant R13MH090623 (JPH). Research reported in this review was supported by NARSAD and Anxiety Disorders Association of America Young Investigator Awards (JJR); NIH grants R01MH087583, R21MH081046, and R21MH 083128 (MK); NIH grant R01MH080394 (LJ); and VISN3 MIRECC, DOD award # W81XWH-06-2-0032, NIH ARRA grant RC1MH088101, and the Lightfighter Trust (RY). NR 147 TC 43 Z9 46 U1 7 U2 40 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1025-3890 J9 STRESS JI Stress PD SEP PY 2011 VL 14 IS 5 BP 481 EP 497 DI 10.3109/10253890.2011.604751 PG 17 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA 808VC UT WOS:000294008400004 PM 21848436 ER PT J AU Agricola, E Arbelot, C Blaivas, M Bouhemad, B Copetti, R Dean, A Dulchavsky, S Elbarbary, M Gargani, L Hoppmann, R Kirkpatrick, AW Lichtenstein, D Liteplo, A Mathis, G Melniker, L Neri, L Noble, VE Petrovic, T Reissig, A Rouby, JJ Seibel, A Soldati, G Storti, E Tsung, JW Via, G Volpicelli, G AF Agricola, Eustachio Arbelot, Charlotte Blaivas, Michael Bouhemad, Belaid Copetti, Roberto Dean, Anthony Dulchavsky, Scott Elbarbary, Mahmoud Gargani, Luna Hoppmann, Richard Kirkpatrick, Andrew W. Lichtenstein, Daniel Liteplo, Andrew Mathis, Gebhard Melniker, Lawrence Neri, Luca Noble, Vicki E. Petrovic, Tomislav Reissig, Angelika Rouby, Jean Jacques Seibel, Armin Soldati, Gino Storti, Enrico Tsung, James W. Via, Gabriele Volpicelli, Giovanni TI Ultrasound performs better than radiographs SO THORAX LA English DT Letter ID TRAUMATIC PNEUMOTHORAX C1 [Kirkpatrick, Andrew W.] Univ Calgary, Foothills Med Ctr, Reg Trauma Serv, Calgary, AB T2N 2T9, Canada. [Agricola, Eustachio] Hosp San Raffaele, I-20132 Milan, Italy. [Arbelot, Charlotte; Bouhemad, Belaid; Rouby, Jean Jacques] Univ Paris 06, Pitie Salpetriere Hosp, F-75252 Paris 05, France. [Blaivas, Michael] Northside Hosp Forsyth, Cumming, GA USA. [Via, Gabriele] Fdn IRCCS Policlin San Matteo, Policlin San Matteo, Pavia, Italy. [Dean, Anthony] Univ Penn, Philadelphia, PA USA. [Dulchavsky, Scott] Henry Ford Hosp, Detroit, MI 48202 USA. [Elbarbary, Mahmoud] King Saud Univ Hlth Sci, Riyadh, Saudi Arabia. [Gargani, Luna] CNR, Pisa, Italy. [Hoppmann, Richard] Univ S Carolina, Columbia, SC 29208 USA. [Lichtenstein, Daniel] Paris Ouest Univ, Paris, France. [Liteplo, Andrew; Noble, Vicki E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mathis, Gebhard] Univ Innsbruck, Rankweil, Austria. [Melniker, Lawrence] New York Methodist Hosp, Brooklyn, NY USA. [Neri, Luca; Storti, Enrico] Osped Niguarda Ca Granda, Milan, Italy. [Petrovic, Tomislav] Univ Paris 13, Paris, France. [Reissig, Angelika] Univ Jena, Jena, Germany. [Seibel, Armin] Diakonie Klinikum, Jung Stilling, Germany. [Soldati, Gino] Valle Serchio Gen Hosp, Lucca, Italy. [Tsung, James W.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Volpicelli, Giovanni] San Luigi Gonzaga Univ Hosp, Turin, Italy. RP Kirkpatrick, AW (reprint author), Univ Calgary, Foothills Med Ctr, Reg Trauma Serv, 1403 29 St NW, Calgary, AB T2N 2T9, Canada. EM andrew.kirkpatrick@albertahealthservices.ca RI Gargani, Luna/C-6187-2015 OI Tsung, James/0000-0002-4718-8325; Gargani, Luna/0000-0002-0716-453X NR 5 TC 14 Z9 14 U1 2 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD SEP PY 2011 VL 66 IS 9 BP 828 EP 829 DI 10.1136/thx.2010.153239 PG 4 WC Respiratory System SC Respiratory System GA 808FM UT WOS:000293962600027 PM 21193568 ER PT J AU Gordon, CR Zor, F Cetrulo, C Brandacher, G Sacks, J Lee, WPA AF Gordon, Chad R. Zor, Fatih Cetrulo, Curtis, Jr. Brandacher, Gerald Sacks, Justin Lee, W. P. Andrew TI Concomitant Face and Hand Transplantation Perfect Solution or Perfect Storm? SO ANNALS OF PLASTIC SURGERY LA English DT Article DE concomitant face hand transplantation; composite tissue allotransplantation; facial allograft; hand allograft; upper extremity allotransplant; composite tissue allograft; Gordon classification ID COMPOSITE TISSUE ALLOTRANSPLANTATION; BLOOD-TRANSFUSION; TACTILE ACUITY; RECOMMENDATIONS; CHALLENGES; CHIMERISM; REJECTION; BLINDNESS; SURVIVAL; BARRIER AB Face and hand composite tissue allotransplantations have evolved into a promising subset of reconstructive transplant surgery due to recent advances in immunotherapy. Concomitant composite tissue allotransplantation, which involves a variable combination of facial (myocutaneous versus osteomyocutaneous) and upper extremity (ie, various levels) composite subtypes, has been performed infrequently at this time. In this review, we will describe many reasons as to why this field remains unexplored. Undoubtedly, future investigation is warranted to investigate the potential advantages and disadvantages of using this approach versus a staged manner for alloreconstruction and to identify the complexities of cortical reorganization and rehabilitation in this setting. C1 [Gordon, Chad R.; Cetrulo, Curtis, Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg,Dept Surg, Boston, MA 02114 USA. [Gordon, Chad R.; Zor, Fatih] Cleveland Clin, Dept Plast Surg, Cleveland, OH 44106 USA. [Gordon, Chad R.; Brandacher, Gerald; Sacks, Justin; Lee, W. P. Andrew] Johns Hopkins Univ, Sch Med, Dept Plast & Reconstruct Surg, Baltimore, MD USA. RP Gordon, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg,Dept Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM cgordon5@partners.org RI Brandacher, Gerald/L-7540-2016; OI Zor, Fatih/0000-0002-5851-0711 NR 44 TC 9 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD SEP PY 2011 VL 67 IS 3 BP 309 EP 314 DI 10.1097/SAP.0b013e31822a2c8f PG 6 WC Surgery SC Surgery GA 806QW UT WOS:000293826100023 PM 21836456 ER PT J AU Bilal, S Haworth, O Wu, LJ Weylandt, KH Levy, BD Kang, JX AF Bilal, Sueleyman Haworth, Oliver Wu, Lijun Weylandt, Karsten H. Levy, Bruce D. Kang, Jing X. TI Fat-1 transgenic mice with elevated omega-3 fatty acids are protected from allergic airway responses SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Omega-3; Resolvins; Protectins; Inflammation; Asthma; Fat-1 mice ID N-3 FATTY-ACIDS; CHRONIC DISEASES; RESOLVIN E1; ASTHMA; INFLAMMATION; RESOLUTION; EOSINOPHIL; MOUSE AB Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been implicated in the alleviation of asthma. Recent studies have demonstrated that the n-3 PUFA derived lipid mediators, protectin D1 and resolvin El, may act as potent resolution agonists in airway inflammation. The effects of the n-3 PUFA tissue status itself on asthma pathogenesis remains to be further investigated. In this study allergic airway inflammation induced by allergen sensitization and aerosol challenge in Fat-1 and wild-type mice was investigated. Fat-1 transgenic mice displayed increased endogenous lung n-3 PUFA. When allergen-sensitized and aerosol-challenged, these animals had decreased airway inflammation with decreased leukocyte accumulation in bronchoalveolar lavage fluid and lung parenchyma. The Fat-1 mice had a shift to the right in the dose-response relationship for methacholine induced bronchoconstriction with a significant increase in the log ED200. The Fat-1 mice had lower BALF concentrations of the pro-inflammatory cytokines IL-1 alpha, IL-2, IL-5, IL-9, IL-13, G-CSF, KC and RANTES. Furthermore, increased lung tissue amounts of the counter-regulatory mediators protectin D1 and resolvin El were found in Fat-1 mice after bronchoprovocative challenge. These results therefore demonstrate a direct protective role for lung n-3 PUFA in allergic airway responses and an increased generation of protectin D1 and resolvin E1 in this context. (C) 2011 Elsevier B.V. All rights reserved. C1 [Bilal, Sueleyman; Weylandt, Karsten H.; Kang, Jing X.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Bilal, Sueleyman; Weylandt, Karsten H.; Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Haworth, Oliver; Levy, Bruce D.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Haworth, Oliver; Levy, Bruce D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bilal, Sueleyman; Weylandt, Karsten H.] Charite, Dept Gastroenterol, D-13353 Berlin, Germany. [Wu, Lijun] Resolvyx Pharmaceut Inc, Bedford, MA 01730 USA. RP Weylandt, KH (reprint author), Massachusetts Gen Hosp, 149-13th St,Room 4433, Charlestown, MA 02129 USA. EM karsten.weylandt@charite.de; blevy@partners.org; jxkang@partners.org OI Bilal, Sueleyman/0000-0002-6390-5451 FU NIH [NIH R01 113605, AI068084]; Boehringer Ingelheim Fonds FX This work was supported by the NIH (NIH R01 113605 to J.X.K. and AI068084 to B.D.L.), and a Boehringer Ingelheim Fonds Travel Grant to S.B. NR 28 TC 45 Z9 47 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD SEP PY 2011 VL 1812 IS 9 BP 1164 EP 1169 DI 10.1016/j.bbadis.2011.05.002 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 805HP UT WOS:000293717800012 PM 21616147 ER PT J AU Espinosa, PS Perez, DL Abner, E Ryan, M AF Espinosa, Patricio S. Perez, David L. Abner, Erin Ryan, Melody TI Association of antiepileptic drugs, vitamin D, and calcium supplementation with bone fracture occurrence in epilepsy patients SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE Antiepileptic drug; Fracture; Seizure; Calcium; Vitamin D; Phenytoin; Lamotrigine ID TERM ANTICONVULSANT THERAPY; MINERAL DENSITY; RISK; OSTEOMALACIA; WOMEN; MONOTHERAPY; METABOLISM; CARBAMAZEPINE; OSTEOPOROSIS; POPULATION AB The aim of this study is to determine whether calcium and vitamin D supplementation reduces the risk of bone fractures in adult epilepsy patients. Records were obtained on 7716 patients with epilepsy prescribed antiepileptic drugs (AED) from the Veteran Affairs Hospital in Lexington, Kentucky. We performed a single center, retrospective cohort study to examine the proportion of fractures in 3303 patients on AED who took supplements compared to patients on AED not taking supplements. Patients prescribed long-term AEDs taking calcium and vitamin D were as likely to have fractures as those who did not take these supplements (11.7% vs. 9.9%, chi(2) = 0.59, p = 0.44). Phenytoin use was associated with a statistically significant increased risk of fractures OR = 1.55 (1.10-2.24). Thus, in this group of patients with epilepsy on AED, bone fractures were not prevented in individuals taking calcium and vitamin D supplementation. (C) 2011 Elsevier B.V. All rights reserved. C1 [Espinosa, Patricio S.] Ctr Int Neurociencias, Mandeville, LA 70471 USA. [Perez, David L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Perez, David L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Abner, Erin] Univ Kentucky, Ctr Aging, Lexington, KY 40506 USA. [Ryan, Melody] Univ Kentucky, Dept Neurol, Lexington, KY 40506 USA. [Ryan, Melody] Univ Kentucky, Coll Pharm, Lexington, KY 40506 USA. RP Espinosa, PS (reprint author), Ctr Int Neurociencias, 5 Finch, Mandeville, LA 70471 USA. EM ps.espinosa@cien-ecuador.org NR 38 TC 8 Z9 8 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 EI 1872-6968 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD SEP PY 2011 VL 113 IS 7 BP 548 EP 551 DI 10.1016/j.clineuro.2011.03.011 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 805KJ UT WOS:000293725000006 PM 21507568 ER PT J AU Power, MC Weuve, J Gagne, JJ McQueen, MB Viswanathan, A Blacker, D AF Power, Melinda C. Weuve, Jennifer Gagne, Joshua J. McQueen, Matthew B. Viswanathan, Anand Blacker, Deborah TI The Association Between Blood Pressure and Incident Alzheimer Disease A Systematic Review and Meta-analysis SO EPIDEMIOLOGY LA English DT Review ID AMYLOID PRECURSOR PROTEIN; VASCULAR RISK-FACTORS; WHITE-MATTER LESIONS; COGNITIVE IMPAIRMENT; METABOLIC SYNDROME; NEUROFIBRILLARY TANGLES; CEREBROVASCULAR-DISEASE; CARDIOVASCULAR-HEALTH; PROSPECTIVE COHORT; BRAIN INFARCTION AB Background: Many epidemiologic studies have considered the association between blood pressure (BP) and Alzheimer disease, yet the relationship remains poorly understood. Methods: In parallel with work on the AlzRisk online database (www.alzrisk.org), we conducted a systematic review to identify all epidemiologic studies meeting prespecified criteria reporting on the association between hypertension, systolic BP, or diastolic BP and incident Alzheimer disease. When possible, we computed summary measures using random-effects models and explored potential heterogeneity related to age at BP assessment. Results: Eighteen studies reporting on 19 populations met the eligibility criteria. We computed summary relative risks (RR(Sigma)) for 3 measures of BP: hypertension (RR(Sigma) = 0.97 [95% confidence interval = 0.80-1.16]); a 10-mm Hg increase in systolic BP (RR(Sigma) = 0.95 [0.91-1.00]); and a 10-mm Hg increase in diastolic BP (RR(Sigma) = 0.94 [0.85-1.04]). We were unable to compute summary estimates for the association between categories of systolic or diastolic BP and Alzheimer disease; however, there did not appear to be a consistent pattern across studies. After stratifying on age at BP assessment, we found a suggestion of an inverse association between late-life hypertension and Alzheimer disease and a suggestion of an adverse association between midlife diastolic hypertension and Alzheimer disease. Conclusions: Based on existing epidemiologic research, we cannot determine whether there is a causal association between BP and Alzheimer disease. Selection bias and reverse causation may account for the suggested inverse association between late-life hypertension on Alzheimer disease, but, given the expected direction of these biases, they are less likely to account for the suggestion that midlife hypertension increases risk. We advocate continuing systematic review; the AlzRisk database entry on this topic (www.alzrisk.org), which was completed in parallel with this work, will be updated as new studies are published. (Epidemiology 2011; 22: 646-659) C1 [Power, Melinda C.] Harvard Univ, Sch Publ Hlth, Landmark Ctr, Dept Epidemiol, Boston, MA 02215 USA. [Power, Melinda C.; Weuve, Jennifer] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. [Weuve, Jennifer] Rush Univ, Inst Healthy Aging, Med Ctr, Chicago, IL 60612 USA. [Weuve, Jennifer] Rush Univ, Dept Internal Med, Med Ctr, Chicago, IL 60612 USA. [Gagne, Joshua J.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Gagne, Joshua J.] Harvard Univ, Sch Med, Boston, MA USA. [McQueen, Matthew B.] Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. [McQueen, Matthew B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Viswanathan, Anand] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Hemorrhag Stroke Res Progr, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Gerontol Res Unit, Boston, MA 02115 USA. RP Power, MC (reprint author), Harvard Univ, Sch Publ Hlth, Landmark Ctr, Dept Epidemiol, 3rd Floor E,POB 15697, Boston, MA 02215 USA. EM mcpower@hsph.harvard.edu FU National Institute of Environmental Health Sciences [T32 ES007069] FX Supported by a grant from an anonymous foundation. Supported by a National Institute of Environmental Health Sciences training grant (T32 ES007069) (to M.C.P.). NR 103 TC 67 Z9 71 U1 4 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2011 VL 22 IS 5 BP 646 EP 659 DI 10.1097/EDE.0b013e31822708b5 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 801NT UT WOS:000293447500010 PM 21705906 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Clinical Efforts to Reduce Myocardial Infarct Size-The Next Step SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article; Proceedings Paper CT Workshop on New Horizons in Cardioprotection CY SEP 20-21, 2010 CL Rockville, MD DE reperfusion; myocardial infarction; ischemic injury; mitochondria ID CORONARY-ARTERY REPERFUSION; NO-REFLOW PHENOMENON; PRECONDITIONING PROTECTS; CONTROLLED-TRIAL; CARDIAC-SURGERY; OCCLUSION; ISCHEMIA; THERAPY; INJURY; HEART AB Prompt myocardial reperfusion reduces infarct size in patients experiencing coronary occlusion. However, its clinical value is limited because reperfusion also causes ischemic myocardial reperfusion injury (IMRI). Considerable research to reduce IMRI has been conducted. Three interventions appear to be promising: 1) myocardial conditioning, which consists of repetitive occlusions of coronary or other arteries prior to or at the time of myocardial reperfusion; 2) the administration of cyclosporine A; and 3) the administration of adenosine. A plan for the testing of these interventions in patients with acute myocardial infarction is described. C1 [Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Dept Med, Div Cardiovasc, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 35 TC 13 Z9 14 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD SEP-DEC PY 2011 VL 16 IS 3-4 BP 349 EP 353 DI 10.1177/1074248411407637 PG 5 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 803QJ UT WOS:000293595500020 PM 21821538 ER PT J AU Jalili, A Moser, A Pashenkov, M Wagner, C Pathria, G Borgdorff, V Gschaider, M Stingl, G Ramaswamy, S Wagner, SN AF Jalili, Ahmad Moser, Anna Pashenkov, Mikhail Wagner, Christine Pathria, Gaurav Borgdorff, Viola Gschaider, Melanie Stingl, Georg Ramaswamy, Sridhar Wagner, Stephan N. TI Polo-Like Kinase 1 Is a Potential Therapeutic Target in Human Melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CELL-CYCLE ARREST; MITOTIC CATASTROPHE; CLINICAL-USE; BI 2536; CANCER; EXPRESSION; PLK1; INHIBITOR; APOPTOSIS; IDENTIFICATION AB Exploration of the human melanoma cell-cycle pathway can lead to identification of new therapeutic targets. By gene set enrichment analysis, we identified the cell-cycle pathway and its member polo-like kinase 1 (Plk-1) to be significantly overexpressed in primary melanomas and in melanoma metastases. In vitro expression of Plk-1 was peaked at the G2/M phase of the cell cycle. Plk-1 knockdown/inhibition led to induction of apoptosis, which was caspase-3/8-dependent and p53-independent, and involved BID and Bcl-2 proteins. Comparative genomic hybridization/single-nucleotide polymorphism arrays showed no genetic alteration in the Plk-1 locus. Previous suggestions and significant enrichment of the mitogen-activated protein kinase (MAPK) signaling pathway pointed to potential regulation of Plk-1 by MAPK signaling. Inhibition of this pathway resulted in decreased Plk-1 expression as a consequence of G1 cell-cycle arrest rather than direct regulation of Plk-1. Inhibition of MAPK and Plk-1 had an additive effect on reduced cell viability. This study shows that in human melanoma, Plk-1 expression is dynamically regulated during the cell cycle, knockdown of Plk-1 leads to apoptotic cell death, and that a combination of Plk-1 and MAPK inhibition has an additive effect on melanoma cell viability. We conclude that combined inhibition of Plk-1 and MAPK could be a potentially attractive strategy in melanoma therapy. C1 [Jalili, Ahmad; Moser, Anna; Pashenkov, Mikhail; Wagner, Christine; Pathria, Gaurav; Borgdorff, Viola; Gschaider, Melanie; Stingl, Georg; Wagner, Stephan N.] Med Univ Vienna, DIAID, Dept Dermatol, A-1090 Vienna, Austria. [Borgdorff, Viola; Wagner, Stephan N.] Austrian Acad Sci, Ctr Mol Med, A-1010 Vienna, Austria. [Ramaswamy, Sridhar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Jalili, A (reprint author), Med Univ Vienna, DIAID, Dept Dermatol, Allgemeines Krankenhaus, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM ahmad.jalili@meduniwien.ac.at OI Wagner, Stephan/0000-0003-4941-7029 FU FWF Austrian Science Fund [L590.B12]; Fund of the City of Vienna FX This work was supported by a FWF Austrian Science Fund grant (L590.B12) to Stephan N Wagner and by the Fund of the City of Vienna for innovative interdisciplinary cancer research to Ahmad Jalili. NR 43 TC 17 Z9 17 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2011 VL 131 IS 9 BP 1886 EP 1895 DI 10.1038/jid.2011.136 PG 10 WC Dermatology SC Dermatology GA 808BO UT WOS:000293948600017 PM 21654832 ER PT J AU Hirsch, J Tarr, R Duckwiler, G Prestigiacomo, CJ AF Hirsch, Joshua Tarr, Robert Duckwiler, Gary Prestigiacomo, Charles J. TI Our specialty's heritage SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material C1 [Tarr, Robert] Univ Hosp Case Med Ctr, Dept Radiol, Cleveland, OH 44106 USA. [Hirsch, Joshua] Massachusetts Gen Hosp, Dept Neurointervent Radiol, Boston, MA 02114 USA. [Duckwiler, Gary] Univ Calif Los Angeles, Med Ctr, Los Angele, CA USA. [Prestigiacomo, Charles J.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol Surg, Newark, NJ 07103 USA. RP Tarr, R (reprint author), Univ Hosp Case Med Ctr, Dept Radiol, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM robert.tarr@uhhospitals.org NR 1 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 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD SEP PY 2011 VL 3 IS 3 BP 212 EP 212 DI 10.1136/neurintsurg-2011-010085 PG 1 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 804YJ UT WOS:000293691300002 PM 21990825 ER PT J AU Pisapia, JM Walcott, BP Nahed, BV Kahle, KT Ogilvy, CS AF Pisapia, Jared M. Walcott, Brian P. Nahed, Brian V. Kahle, Kristopher T. Ogilvy, Christopher S. TI Cerebral revascularization for the treatment of complex intracranial aneurysms of the posterior circulation: microsurgical anatomy, techniques and outcomes SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID INFERIOR CEREBELLAR ARTERY; PIPELINE EMBOLIZATION DEVICE; VEIN BYPASS GRAFTS; EC-IC BYPASS; VERTEBRAL ARTERY; SURGICAL-TREATMENT; ARTERIOVENOUS MALFORMATION; SUBARACHNOID HEMORRHAGE; ENDOVASCULAR TREATMENT; DISSECTING ANEURYSMS AB While the trend for endovascular therapy of posterior circulation aneurysms is permeating, cerebrovascular bypass remains essential in the armamentarium for complex lesions not amendable to these techniques. This review discusses the microsurgical anatomy of the posterior fossa intracranial circulation, as well as the techniques and outcomes related to cerebrovascular bypass. C1 [Pisapia, Jared M.] Univ Penn, Dept Neurol Surg, Philadelphia, PA 19104 USA. [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.; Ogilvy, Christopher S.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. [Walcott, Brian P.; Nahed, Brian V.; Kahle, Kristopher T.; Ogilvy, Christopher S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Walcott, BP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM bwalcott@partners.org NR 69 TC 3 Z9 4 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD SEP PY 2011 VL 3 IS 3 BP 249 EP 254 DI 10.1136/jnis.2010.004176 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 804YJ UT WOS:000293691300013 PM 21990836 ER PT J AU Miguel, K Hirsch, JA Sheridan, RM AF Miguel, Karen Hirsch, Joshua A. Sheridan, Robert M. TI Team training: a safer future for neurointerventional practice SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article AB As medical errors and patient harm mount in today's healthcare arena, healthcare administrators have turned to high efficiency, high reliability, and high risk industries for strategies and guidance. By adopting elements of Crew Resource Management (CRM), healthcare teams have been shown to work more effectively together, allowing for earlier recognition of medical errors and catching them before they cause serious patient harm. C1 [Miguel, Karen; Hirsch, Joshua A.; Sheridan, Robert M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Miguel, K (reprint author), Massachusetts Gen Hosp, 175 Cambridge St, Boston, MA 02114 USA. EM kmiguel@partners.org NR 10 TC 4 Z9 4 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD SEP PY 2011 VL 3 IS 3 BP 285 EP 287 DI 10.1136/jnis.2010.003590 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 804YJ UT WOS:000293691300020 PM 21990843 ER PT J AU Ammirati, M Spiliopoulos, K Epstein, CR Gabriel, J Bourekas, EC AF Ammirati, Mario Spiliopoulos, Konstantinos Epstein, Clara Raquel Gabriel, Josue Bourekas, Eric C. TI Preoperative direct percutaneous embolization of spinal metastasis from renal cell carcinoma SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article AB Preoperative direct percutaneous embolization has been very rarely used in hypervascular metastatic spinal tumors to decrease blood loss during the surgery. A patient is presented with solitary spinal metastasis due to renal cell carcinoma who underwent a two-stage spondylectomy. Transarterial tumor embolization with polyvinyl alcohol (PVA) particles and liquid coil placement, and percutaneous tumor embolization with PVA particles were used before the first and the second stage, respectively. C1 [Bourekas, Eric C.] Ohio State Univ, Med Ctr, Dept Radiol, Sect Diagnost & Intervent Neuroradiol,Coll Med, Columbus, OH 43210 USA. [Ammirati, Mario; Epstein, Clara Raquel; Bourekas, Eric C.] Ohio State Univ, Coll Med, Dept Neurol Surg, Columbus, OH 43210 USA. [Spiliopoulos, Konstantinos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Gabriel, Josue] Ohio State Univ, Coll Med, Dept Orthoped, Columbus, OH 43210 USA. RP Bourekas, EC (reprint author), Ohio State Univ, Med Ctr, Dept Radiol, Sect Diagnost & Intervent Neuroradiol,Coll Med, 395 W 12th Ave,Rm 468, Columbus, OH 43210 USA. EM eric.bourekas@osumc.edu NR 8 TC 2 Z9 2 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD SEP PY 2011 VL 3 IS 3 BP 297 EP 299 DI 10.1136/jnis.2010.003699 PG 3 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 804YJ UT WOS:000293691300024 PM 21990847 ER PT J AU Babu, MA Coumans, JVC Carter, BS Taylor, WR Kasper, EM Roitberg, BZ Krauss, WE Chen, CC AF Babu, Maya A. Coumans, Jean-Valery C. Carter, Bob S. Taylor, William R. Kasper, Ekkehard M. Roitberg, Ben Z. Krauss, William E. Chen, Clark C. TI A review of lumbar spinal instrumentation: evidence and controversy SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Review ID PEDICLE SCREW INSTRUMENTATION; FUSION; STENOSIS; SURGERY; TRENDS; SPONDYLOLISTHESIS; COMPLICATIONS; MANAGEMENT; TRAUMA; ADULTS AB Disability secondary to disorders of the spine is a significant problem worldwide. In the USA, there has been a recent surge in the costs associated with caring for spinal pathology; from 1997 to 2005, there was a growth of 65% in healthcare expenditures on spinal disease, totalling $86 billion in 2005. Increasingly, there has been media and public scrutiny over the rapid rise in the volume of procedures with spinal instrumentation; some have suggested that this rise has been fuelled by non-medical drivers such as the financial incentives involved with the use of instrumentation; others suggest that innovation in spine technology and devices has led to improved options for the treatment of spine pathology. In this context, we conducted a review of the literature to assess the use of instrumentation in lumbar procedures and its relationship to successful fusion and patient outcome. Our review suggests that there is data supporting the thesis that lumbar instrumentation improves rates of fusion. However, there is no consistent correlation between increased rates of fusion and improved patient outcomes. C1 [Chen, Clark C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Neurosurg,Beth Israel Deaconess Hosp, Boston, MA 02115 USA. [Babu, Maya A.; Krauss, William E.] Mayo Clin, Dept Neurol Surg, Rochester, MN USA. [Coumans, Jean-Valery C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Carter, Bob S.; Taylor, William R.] Univ Calif San Diego, Div Neurosurg, San Diego, CA 92103 USA. [Roitberg, Ben Z.] Univ Chicago, Neurosurg Sect, Chicago, IL 60637 USA. RP Chen, CC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Neurosurg,Beth Israel Deaconess Hosp, Jimmy Fund 620A,44 Binney St, Boston, MA 02115 USA. EM cchen1@partners.org NR 23 TC 7 Z9 7 U1 0 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 SEP PY 2011 VL 82 IS 9 BP 948 EP 951 DI 10.1136/jnnp.2010.231860 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 803PN UT WOS:000293593300032 PM 21602520 ER PT J AU D'Amore, MM Cheng, DM Kressin, NR Jones, J Samet, JH Winter, M Kim, TW Saitz, R AF D'Amore, Meredith M. Cheng, Debbie M. Kressin, Nancy R. Jones, Judith Samet, Jeffrey H. Winter, Michael Kim, Theresa W. Saitz, Richard TI Oral health of substance-dependent individuals: Impact of specific substances SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Oral health; Substance dependence; Dental care ID PERIODONTAL-DISEASE; DENTAL-HEALTH; DRUG-USERS; ADDICTION; ABUSE; DENTISTRY; VETERANS; BEHAVIOR; CARIES; RISK AB Little is known about how different types of substances affect oral health. Our objective was to examine the respective effects of alcohol, stimulants, opioids, and marijuana on oral health in substance-dependent persons. Using self-reported data from 563 substance-dependent individuals, we found that most reported unsatisfactory oral health, with their most recent dental visit more than I year ago. In multivariable logistic regressions, none of the substance types were significantly associated with oral health status. However, opioid use was significantly related to a worse overall oral health rating compared to I year ago. These findings highlight the poor oral health of individuals with substance dependence and the need to address declining oral health among opioid users. General health and specialty addiction care providers should be aware of oral health problems among these patients. In addition, engagement into addiction and medical care may be facilitated by addressing oral health concerns. (C) 2011 Elsevier Inc. All rights reserved. C1 [D'Amore, Meredith M.; Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Hlth Care Dispar Res Program,Boston Med Ctr, Boston, MA 02118 USA. [Cheng, Debbie M.; Samet, Jeffrey H.; Kim, Theresa W.; Saitz, Richard] Boston Univ, Sch Med, Gen Internal Med Sect, Clin Addict Res & Educ CARE Unit, Boston, MA 02118 USA. [Cheng, Debbie M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Kressin, Nancy R.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. [Jones, Judith] Boston Univ, Henry M Goldman Sch Dent Med, Boston, MA 02118 USA. [Samet, Jeffrey H.] Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA 02118 USA. [Winter, Michael] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Saitz, Richard] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP D'Amore, MM (reprint author), 801 Massachusetts Ave,2098, Boston, MA 02113 USA. EM meredith.damore@bmc.org OI Samet, Jeffrey/0000-0002-0897-3400; Kressin, Nancy/0000-0003-2767-4286; Jones, Judith/0000-0002-0126-0790; Kim, Theresa/0000-0001-6043-0721; /0000-0002-2535-1427 FU NCRR NIH HHS [UL1 RR025771]; NIAAA NIH HHS [R01 AA010870]; NIDA NIH HHS [R01 DA010019]; NIDCR NIH HHS [K24 DE018211] NR 54 TC 8 Z9 9 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD SEP PY 2011 VL 41 IS 2 BP 179 EP 185 DI 10.1016/j.jsat.2011.02.005 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 803TF UT WOS:000293603500008 PM 21474269 ER PT J AU Perkins, AC Cheng, CE Hillebrand, GG Miyamoto, K Kimball, AB AF Perkins, A. C. Cheng, C. E. Hillebrand, G. G. Miyamoto, K. Kimball, A. B. TI Comparison of the epidemiology of acne vulgaris among Caucasian, Asian, Continental Indian and African American women SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Article DE acne sequelae; acne vulgaris; epidemiology; ethnicity; race ID CUTANEOUS DISEASES; FACIAL ACNE; ETHNIC SKIN; COLOR; PREVALENCE AB Background Acne vulgaris is a common skin disease with a large quality of life impact, characterized by comedones, inflammatory lesions, secondary dyspigmentation and scarring. There are few large objective studies comparing acne epidemiology between racial and ethnic groups. Objective This study aimed to define the prevalence and subtypes of acne in women of different racial groups from four ethnicities. Methods The sample consisted of 2895 (384 African American, 520 Asian, 1295 Caucasian, 258 Hispanic and 438 Continental Indian) women ranging in age from 10 to 70 years. Photographs of subjects were graded for acne lesions, scars, dyspigmentation, and measurements taken of sebum excretion and pore size. Results Clinical acne was more prevalent in African American and Hispanic women (37%, 32% respectively) than in Continental Indian, Caucasian and Asian (23%, 24%, 30% respectively) women. All racial groups displayed equal prevalence of both subtypes of acne with the exception of Asians, for whom inflammatory acne was more prevalent than comedonal (20% vs. 10%) acne, and in Caucasians, for whom comedonal acne was more prevalent than inflammatory (14% vs. 10%) acne. Hyperpigmentation was more prevalent in African American and Hispanic (65%, 48% respectively) than in Asian, Continental Indian and Caucasian (18%, 10%, 25% respectively) women. Dyspigmentation and atrophic scarring were more common in African American and Hispanic women than in all other ethnicities. There was a negative correlation between pore size and skin lightness for all ethnicities. Sebum production was positively correlated with acne severity in African American, Asian and Hispanic women, and pore size was positively correlated with acne in African American, Asian and Continental Indian women, (for all above results, P < 0.05). Limitations Only female participants were recruited. Data collection was restricted to four cities, with some ethnicities from single cities. Acne was evaluated only on the left side of the face and the two-dimensional nature of photography may not capture all skin surface changes. Conclusion Acne prevalence and sequelae were more common in those with darker skin types, suggesting that acne is a more heterogeneous condition than previously described and highlight the importance of skin-colour tailored treatment. C1 [Perkins, A. C.; Cheng, C. E.; Kimball, A. B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Hillebrand, G. G.; Miyamoto, K.] Procter & Gamble, Cincinnati, OH USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Procter Gamble; Doris Duke Clinical Research Foundation FX This study was funded in part by an unrestricted grant from Procter & Gamble. Alexis Perkins received fellowship funding from the Doris Duke Clinical Research Foundation. NR 26 TC 27 Z9 27 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0926-9959 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD SEP PY 2011 VL 25 IS 9 BP 1054 EP 1060 DI 10.1111/j.1468-3083.2010.03919.x PG 7 WC Dermatology SC Dermatology GA 803BZ UT WOS:000293556400009 PM 21108671 ER PT J AU Funalot, B Topilko, P Arroyo, MAR Sefiani, A Hedley-Whyte, ET Yoldi, ME Richard, L Cros, D Magdelaine, C Sturtz, FG Urtizberea, JA Charnay, P Bragado, FG Vallat, JM AF Funalot, B. Topilko, P. Arroyo, M. A. R. Sefiani, A. Hedley-Whyte, E. T. Yoldi, M. E. Richard, L. Cros, D. Magdelaine, C. Sturtz, F. G. Urtizberea, J. A. Charnay, P. Bragado, F. G. Vallat, J-M TI HOMOZYGOUS DELETION OF AN EGR2 TRANSCRIPTIONAL ENHANCER IN A PATIENT WITH CONGENITAL AMYELINATING NEUROPATHY SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Meeting of the Peripheral-Nerve-Society CY JUN 25-29, 2011 CL Potomac, MD SP Peripheral Nerve Soc C1 [Funalot, B.; Vallat, J-M] Ctr Hosp Univ Limoges, Ctr Reference Neuropathies Peripher Rares, Limoges, France. [Funalot, B.; Richard, L.; Vallat, J-M] Ctr Hosp Univ Limoges, Serv & Lab Neurol, Limoges, France. [Funalot, B.; Magdelaine, C.; Sturtz, F. G.] Ctr Hosp Univ Limoges, Serv Biochim & Genet Mol, Limoges, France. [Funalot, B.; Richard, L.; Magdelaine, C.; Sturtz, F. G.; Vallat, J-M] Univ Limoges, Fac Med, Equipe Accueil 4021, Limoges, France. [Topilko, P.] Ecole Normale Super, CNRS, INSERM, IBENS,UMR 8197,U1024, Paris, France. [Arroyo, M. A. R.] Hosp Virgen Camino, Serv Navarro Salud Osasunbidea, Serv Genet Med, Pamplona, Spain. [Sefiani, A.] Univ Mohamed V Souissi, Fac Med & Pharm, Ctr Genom Humaine, Rabat, Morocco. [Hedley-Whyte, E. T.] Massachusetts Gen Hosp, Neuropathol Lab, CS Kubik, Boston, MA 02114 USA. [Hedley-Whyte, E. T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Yoldi, M. E.] Hosp Virgen Camino, Serv Navarro Salud Osasunbidea, Serv Pediatr11a, Pamplona, Spain. [Cros, D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Urtizberea, J. A.] Hop Marin Assistance Publ Hop Paris, Hendaye, France. [Bragado, F. G.] Hosp Virgen Camino, Serv Navarro Salud Osasunbidea, Serv Anat Patol, Pamplona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD SEP PY 2011 VL 16 SU 3 BP S43 EP S44 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 802KS UT WOS:000293510300095 ER PT J AU Laura, M Eichler, FS Hornemann, T Polke, J Davis, M Bull, K Houlden, H Reilly, MM AF Laura, M. Eichler, F. S. Hornemann, T. Polke, J. Davis, M. Bull, K. Houlden, H. Reilly, M. M. TI HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY TYPE 1: CORRELATION OF SEVERITY AND PLASMA ATYPICAL DEOXY-SPHYNGOID BASES SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Meeting of the Peripheral-Nerve-Society CY JUN 25-29, 2011 CL Potomac, MD SP Peripheral Nerve Soc C1 [Laura, M.; Bull, K.; Houlden, H.; Reilly, M. M.] UCL Inst Neurol, Ctr Neuromuscular Dis, London, England. [Eichler, F. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hornemann, T.] Univ Zurich Hosp, Inst Clin Chem, CH-8091 Zurich, Switzerland. [Polke, J.; Davis, M.] Natl Hosp Neurol & Neurosurg, Neurogenet Unit, London WC1N 3BG, England. RI Reilly, Mary/C-8482-2013; Houlden, Henry/C-1532-2008 OI Houlden, Henry/0000-0002-2866-7777 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD SEP PY 2011 VL 16 SU 3 BP S72 EP S73 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 802KS UT WOS:000293510300159 ER PT J AU Oaklander, AL Klein, MM AF Oaklander, A. L. Klein, M. M. TI JUVENILE-ONSET SMALL-FIBER POLYNEUROPATHY: A TREATABLE CAUSE OF CHRONIC PAIN AND MULTI-SOMATIC COMPLAINTS IN THE YOUNG SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Meeting of the Peripheral-Nerve-Society CY JUN 25-29, 2011 CL Potomac, MD SP Peripheral Nerve Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD SEP PY 2011 VL 16 SU 3 BP S100 EP S101 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 802KS UT WOS:000293510300218 ER PT J AU Dransfield, MT Cockcroft, JR Townsend, RR Coxson, HO Sharma, SS Rubin, DB Emmett, AH Cicale, MJ Crater, GD Martinez, FJ AF Dransfield, Mark T. Cockcroft, John R. Townsend, Raymond R. Coxson, Harvey O. Sharma, Sanjay S. Rubin, David B. Emmett, Amanda H. Cicale, Michael J. Crater, Glenn D. Martinez, Fernando J. TI Effect of fluticasone propionate/salmeterol on arterial stiffness in patients with COPD SO RESPIRATORY MEDICINE LA English DT Article DE Augmentation index; Computed tomography scanning; Emphysema; Aortic pulse wave velocity ID OBSTRUCTIVE PULMONARY-DISEASE; PULSE-WAVE VELOCITY; LUNG-FUNCTION; CARDIOVASCULAR EVENTS; AUGMENTATION INDEX; RISK; INFLAMMATION; EMPHYSEMA; CORTICOSTEROIDS; MORTALITY AB Background: COPD is associated with increased arterial stiffness which may in part explain the cardiovascular morbidity observed in the disease. A causal relationship between arterial stiffness and cardiovascular events has not been established, though their strong association raises the possibility that therapies that reduce arterial stiffness may improve cardiovascular outcomes. Prior studies suggest that fluticasone propionate/salmeterol (FSC) may improve cardiovascular outcomes in COPD and we hypothesized that FSC would reduce arterial stiffness in these patients. Methods: This multicenter, randomized, double-blind, placebo-controlled study compared the effects of FSC 250/50 mu g twice-daily and placebo on aortic pulse wave velocity (aPWV) as determined by ECG-gated carotid and femoral artery waveforms. The primary endpoint was aPWV change from baseline at 12-weeks (last measure for each patient). Results: 249 patients were randomized; the mean FEV(1) in each group was similar (55% predicted) and 60% of patients reported a cardiovascular disorder. At 12-weeks, aPWV between FSC and placebo was -0.42 m/s (95%CI -0.88, 0.03; p = 0.065). A statistically significant reduction in aPWV between FSC and placebo was observed in those who remained on study drug throughout the treatment period [-0.49 m/s (95%CI 0.98, -0.01; p = 0.045)]. A post hoc analysis suggested the effect of FSC was greater in patients with higher baseline aPWV. Conclusion: FSC does not reduce aPWV in all patients with moderate to severe COPD, but may have effects in those with elevated arterial stiffness. Additional studies are required to determine if aPWV could serve as a surrogate for cardiovascular events in COPD. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Dransfield, Mark T.] Univ Alabama, Univ Alabama Birmingham Lung Hlth Ctr, Birmingham VA Med Ctr, Birmingham, AL USA. [Cockcroft, John R.] Univ Hosp, Wales Heart Res Inst, Dept Cardiol, Cardiff CF14 4XN, S Glam, Wales. [Townsend, Raymond R.] Univ Penn, Sch Med, Dept Med, Hypertens Program, Philadelphia, PA 19104 USA. [Coxson, Harvey O.] Univ British Columbia, Vancouver Gen Hosp, Dept Radiol, Vancouver, BC V5Z 1M9, Canada. [Coxson, Harvey O.] Univ British Columbia, Vancouver Gen Hosp, UBC James Hogg Res Ctr, Vancouver, BC V5Z 1M9, Canada. [Sharma, Sanjay S.; Rubin, David B.; Emmett, Amanda H.; Cicale, Michael J.; Crater, Glenn D.] GlaxoSmithKline Inc, Resp & Immunoinflammat Med Dev Ctr, Res Triangle Pk, NC USA. [Martinez, Fernando J.] Univ Michigan Hlth Syst, Div Pulm & Crit Care Med, Ann Arbor, MI USA. RP Dransfield, MT (reprint author), Univ Alabama, Univ Alabama Birmingham Lung Hlth Ctr, Birmingham VA Med Ctr, Birmingham, AL USA. EM mdransfield99@msn.com RI Coxson, Harvey/A-9861-2017; OI Coxson, Harvey/0000-0001-5750-9711; Crater, Glenn/0000-0002-1159-1323 FU GlaxoSmithKline, Research Triangle Park, NC [NCT00857766]; NHLBI; Aeris; Altana/Nycomed/Forest; AstraZeneca; Boehringer Ingelheim; Novartis; Pfizer; Roche; UpToDate; Associates in Medical Marketin; Castle Connolly FX This study (NCT00857766) was funded by GlaxoSmithKline, Research Triangle Park, NC. All authors were involved with the initial concept of the paper, were extensively involved with the writing, and retained full editorial control throughout the development of the manuscript. Final approval was solely endorsed by the authors. All authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. The authors did not receive any money for writing the manuscript. MTD has received COPD-related research funding from the NHLBI as well as Aeris, Altana/Nycomed/Forest, AstraZeneca, Boehringer Ingelheim, GSK, Novartis, Pfizer, and Roche. He has served on an advisory board for GSK and BI and has received speakers' honoraria from GSK and BI for COPD-related talks. JRC is a PI for the ARCADE Study and a member of GSK advisory board for GSK UK. RRT serves as a consultant to GlaxoSmithKline, Merck and Novartis and receives royalties from UpToDate. HOC has received an honorarium for serving on the steering committee for the ECLIPSE project for GSK. In addition he was the co-investigator on two multi-center studies sponsored by GSK and has received travel expenses to attend meetings related to the project. He has a contract service agreement with GSK to quantify the CT scans in subjects with COPD and a service agreement with Spiration Inc to measure changes in lung volume in subjects with severe emphysema. He has received a fee for speaking at a conference and related travel expenses from AstraZeneca (Australia). FJM has served on Advisory Boards relating to COPD related topics for GSK, MedImmune/AstraZeneca, Ikaria, Merck, Pearl, Novartis, UBC, Forest/Almirall. He has consulted for Boehringer Ingelheim, Nycomed/Forest, Roche, Bayer, Schering, HLS, Talecris, Comgenix, fb Communications, Boom Comm and Actelion. He has served on Speaker's Bureaus for GSK, NACE, Med Ed, Potomac, Pfizer, Boehringer Ingelheim, Schering, Vox Medic, American Lung Association, WebMD, ePocrates, AstraZeneca, France Foundation and Altana /Nycomed. His institution has received funds from Boehringer Ingelheim for a clinical trial. He has received royalties from Associates in Medical Marketin and Castle Connolly. He has developed educational materials for the France Foudation, HIT Global and ePocrates. He has served on Steering Committees for clinical trials supported by GSK, Nycomed, and Actelion. MJC was an employee of GlaxoSmithKline at the time the manuscript was written. SSS, GDC, DBR, and AHE are all employees of GlaxoSmithKline and own stock in the company. NR 34 TC 16 Z9 16 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD SEP PY 2011 VL 105 IS 9 BP 1322 EP 1330 DI 10.1016/j.rmed.2011.05.016 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 805JX UT WOS:000293723800009 PM 21696934 ER PT J AU Ivanovic, T Boulant, S Ehrlich, M Demidenko, AA Arnold, MM Kirchhausen, T Nibert, ML AF Ivanovic, Tijana Boulant, Steeve Ehrlich, Marcelo Demidenko, Aleksander A. Arnold, Michelle M. Kirchhausen, Tomas Nibert, Max L. TI Recruitment of Cellular Clathrin to Viral Factories and Disruption of Clathrin-Dependent Trafficking SO TRAFFIC LA English DT Article DE adaptor; clathrin; membrane trafficking; reovirus; viral factories ID PROTEIN MU-NS; REOVIRUS SIGMA-NS; MAMMALIAN REOVIRUSES; MITOTIC SPINDLE; CORE PARTICLES; BETA-PROPELLER; RNA-SYNTHESIS; COATED PITS; CELLS; ENDOCYTOSIS AB The viral factories of mammalian reovirus ( MRV) are cytoplasmic structures that serve as sites of viral genome replication and particle assembly. A 721-aa MRV nonstructural protein, mu NS, forms the factory matrix and recruits other viral proteins to these structures. In this report, we show that mu NS contains a conserved C-proximal sequence (711-LIDFS-715) that is similar to known clathrin-box motifs and is required for recruitment of clathrin to viral factories. Clathrin recruitment by mu NS occurs independently of infecting MRV particles or other MRV proteins. Ala substitution for a single Leu residue ( mutation L711A) within the putative clathrin-binding motif of mu NS inhibits clathrin recruitment, but does not prevent formation or expansion of viral factories. Notably, clathrin-dependent cellular functions, including both endocytosis and secretion, are disrupted in cells infected with MRV expressing wild-type, but not L711A, mu NS. These results identify mu NS as a novel adaptor-like protein that recruits cellular clathrin to viral factories, disrupting normal functions of clathrin in cellular membrane trafficking. To our knowledge, this is the only viral or bacterial protein yet shown to interfere with clathrin functions in this manner. The results additionally establish a new approach for studies of clathrin functions, based on mu NS-mediated sequestration. C1 [Boulant, Steeve; Ehrlich, Marcelo; Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Ivanovic, Tijana; Boulant, Steeve; Demidenko, Aleksander A.; Arnold, Michelle M.; Nibert, Max L.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Ivanovic, Tijana] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ivanovic, Tijana; Arnold, Michelle M.; Nibert, Max L.] Harvard Univ, Div Med Sci, Program Virol, Boston, MA 02115 USA. [Boulant, Steeve; Ehrlich, Marcelo; Kirchhausen, Tomas] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu; mnibert@hms.harvard.edu FU NIH [R01 GM36548, R01 AI47904, R56 AI067445, T32 AI07245] FX We thank Elaine Freimont for technical support; other lab members for discussions; and Melina Agosto, Cathy Eichwald, Cathy Miller and John Parker for comments on an early manuscript. We also thank Jim Chappell, Terry Dermody and Takeshi Kobayashi (Vanderbilt University) for reagents and advice for plasmid-based rescue of MRV and Megan Stanifer for assistance in generating Figure S2. This research was supported by NIH grants R01 GM36548 to T. K. and R01 AI47904 and R56 AI067445 to M. L. N. Support was also provided by the Bill and Melinda Gates Foundation through a Collaboration for AIDS Vaccine Discovery grant to a Vaccine Discovery Consortium (including M. L. N.) headed by the International AIDS Vaccine Initiative. T. I. and M. M. A. received initial support from NIH training grant T32 AI07245, and M. E. was additionally supported by a Dorit fellowship from Harvard Medical School. NR 60 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD SEP PY 2011 VL 12 IS 9 BP 1179 EP 1195 DI 10.1111/j.1600-0854.2011.01233.x PG 17 WC Cell Biology SC Cell Biology GA 806HP UT WOS:000293797200008 PM 21736684 ER PT J AU Weiser, TG Semel, ME Simon, AE Lipsitz, SR Haynes, AB Funk, LM Berry, WR Gawande, AA AF Weiser, Thomas G. Semel, Marcus E. Simon, Alan E. Lipsitz, Stuart R. Haynes, Alex B. Funk, Luke M. Berry, William R. Gawande, Atul A. TI In-hospital Death following Inpatient Surgical Procedures in the United States, 1996-2006 SO WORLD JOURNAL OF SURGERY LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; SURGERY; MORTALITY; SAFETY; RISK AB Over the past decade, improvements in perioperative care have been widely introduced throughout the United States, yet there is no clear indication that the death rate following surgery has improved. We sought to evaluate the number of deaths after surgery in the United States over a 10-year period and to evaluate trends in postoperative mortality. Using the National Hospital Discharge Survey, we identified patients who underwent a surgical procedure and subsequently died in the hospital within 30 days of admission. In 1996 there were 12,250,000 hospitalizations involving surgery, rising to 13,668,000 in 2006. Postoperative deaths, however, declined during this same period, from 201,000 to 156,000 (P < 0.01), giving a postoperative in-hospital death ratio (death per hospitalization) of 1.64 and 1.14% (P < 0.001), respectively, for the two time frames. The death rate following surgery is substantial but appears to have improved. Such mortality statistics provide an essential measure of the public health impact of surgical care. Incorporating mortality statistics following therapeutic intervention is an essential strategy for regional and national surveillance of care delivery. C1 [Weiser, Thomas G.; Semel, Marcus E.; Funk, Luke M.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Semel, Marcus E.; Funk, Luke M.; Berry, William R.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Simon, Alan E.] Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Lipsitz, Stuart R.; Berry, William R.; Gawande, Atul A.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Haynes, Alex B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Gawande, AA (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM safesurgery@hsph.harvard.edu RI Haynes, Alex/K-1446-2013; OI Haynes, Alex/0000-0002-5731-329X; Gawande, Atul/0000-0002-1824-9176 NR 26 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD SEP PY 2011 VL 35 IS 9 BP 1950 EP 1956 DI 10.1007/s00268-011-1169-5 PG 7 WC Surgery SC Surgery GA 805DB UT WOS:000293705500002 PM 21732207 ER PT J AU Yehuda, R AF Yehuda, Rachel TI Are Different Biological Mechanisms Involved in the Transmission of Maternal Versus Paternal Stress-Induced Vulnerability to Offspring? SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID HOLOCAUST SURVIVORS; EXPOSURE C1 [Yehuda, Rachel] Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Yehuda, Rachel] Mt Sinai Sch Med, Traumat Stress Studies Div, Dept Psychiat, Bronx, NY 10468 USA. RP Yehuda, R (reprint author), Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, 526 OOMH PTSD 116-A,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov FU NIMH NIH HHS [5RC1MH088101-02] NR 11 TC 7 Z9 7 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2011 VL 70 IS 5 BP 402 EP 403 DI 10.1016/j.biopsych.2011.07.001 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 803JE UT WOS:000293576800007 PM 21820529 ER PT J AU Kramer, DB Zimetbaum, PJ AF Kramer, Daniel B. Zimetbaum, Peter J. TI Long-QT Syndrome SO CARDIOLOGY IN REVIEW LA English DT Review DE long QT syndrome; sudden cardiac death ID TORSADE-DE-POINTES; GENOTYPE-PHENOTYPE CORRELATION; CARDIAC-ARRHYTHMIAS; MENSTRUAL-CYCLE; MOLECULAR-BASIS; LQT2 FORMS; HEART-RATE; EXERCISE; INTERVAL; RISK AB Acquired and hereditary long-QT syndromes are important causes of sudden cardiac death. Both categories are characterized by abnormally prolonged cardiac repolarization arising from a complex interaction between genetic and environmental factors. This produces a potentially dangerous substrate for polymorphic ventricular tachycardia and sudden cardiac death. In this review, the pathophysiologic, diagnostic, and prognostic features of long-QT syndromes, as well as recommendations regarding therapy, are reviewed. C1 [Kramer, Daniel B.; Zimetbaum, Peter J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Sch Med,Dept Med, Boston, MA 02215 USA. RP Kramer, DB (reprint author), BIDMC W Campus Baker 4,185 Pilgrim Rd, Boston, MA 02215 USA. EM dkramer@bidmc.harvard.edu NR 52 TC 21 Z9 21 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1061-5377 J9 CARDIOL REV JI Cardiol. Rev. PD SEP-OCT PY 2011 VL 19 IS 5 BP 217 EP 225 DI 10.1097/CRD.0b013e3182203504 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 800TY UT WOS:000293391500001 PM 21808164 ER PT J AU Aronis, KN Diakopoulos, KN Fiorenza, CG Chamberland, JP Mantzoros, CS AF Aronis, K. N. Diakopoulos, K. N. Fiorenza, C. G. Chamberland, J. P. Mantzoros, C. S. TI Leptin administered in physiological or pharmacological doses does not regulate circulating angiogenesis factors in humans SO DIABETOLOGIA LA English DT Article DE Angiogenesis; Angiogenin; Angiopoietin-1; Humans; Leptin; MMP9 ID ENDOTHELIAL-CELL PROLIFERATION; METHIONYL HUMAN LEPTIN; DIABETIC OB/OB MICE; HYPOTHALAMIC AMENORRHEA; NONALCOHOLIC STEATOHEPATITIS; INTIMAL NEOVASCULARIZATION; POTENTIAL ROLE; IN-VITRO; GROWTH; EXPRESSION AB Leptin has been shown to regulate angiogenesis in animal and in vitro studies by upregulating the production of several pro-angiogenic factors, but its role in regulating angiogenesis has never been studied in humans. The potential angiogenic effect of two doses of metreleptin (50 and 100 ng/ml) was evaluated in vitro, using a novel three-dimensional angiogenesis assay. Fifteen healthy, normoleptinaemic volunteers were administered both a physiological (0.1 mg/kg) and a pharmacological (0.3 mg/kg) single dose of metreleptin, in vivo, on two different inpatient admissions separated by 1-12 weeks. Serum was collected at 0, 6, 12 and 24 h after metreleptin administration. Twenty lean women, with leptin levels < 5 ng/ml, were randomised in a 1:1 fashion to receive either physiological replacement doses of metreleptin (0.04-0.12 mg/kg q.d.) or placebo for 32 weeks. Serum was collected at 0, 8, 20 and 32 weeks after randomisation. Proteomic angiogenesis array analysis was performed to screen for angiogenic factors. Circulating concentrations of angiogenin, angiopoietin-1, platelet derived endothelial factor (PDGF)-AA, matrix metalloproteinase (MMP) 8 and 9, endothelial growth factor (EGF) and vascular EGF (VEGF) were also measured. Both metreleptin doses failed to induce angiogenesis in the in vitro model. Although leptin levels increased significantly in response to both short-term and long-term metreleptin administration, circulating concentrations of angiogenesis markers did not change significantly in vivo. This is the first study that examines the effect of metreleptin administration in angiogenesis in humans. Metreleptin administration does not regulate circulating angiogenesis related factors in humans. ClinicalTrials.gov NCT00140205 and NCT00130117. This study was supported by National Institutes of Health-National Center for Research Resources grant M01-RR-01032 (Harvard Clinical and Translational Science Center) and grant number UL1 RR025758. Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785, 79929 and 81913, and AG032030. C1 [Mantzoros, C. S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Aronis, K. N.; Diakopoulos, K. N.; Fiorenza, C. G.; Chamberland, J. P.; Mantzoros, C. S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Mantzoros, C. S.] Harvard Univ, Boston VA Healthcare Syst, Endocrinol Sect, Sch Med, Boston, MA 02215 USA. RP Mantzoros, CS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. EM cmantzor@bidmc.harvard.edu RI Aronis, Konstantinos/F-3586-2012; OI Aronis, Konstantinos/0000-0001-7189-8434; Chamberland, John/0000-0002-7862-1371; Diakopoulos, Kalliope/0000-0002-9236-0489 FU National Institutes of Health-National Center for Research Resources [M01-RR-01032, UL1 RR025758]; National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913, AG032030] FX This study was supported by National Institutes of Health-National Center for Research Resources grant M01-RR-01032 (Harvard Clinical and Translational Science Center) and grant number UL1 RR025758. Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785, 79929 and 81913, and AG032030. NR 46 TC 8 Z9 9 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2011 VL 54 IS 9 BP 2358 EP 2367 DI 10.1007/s00125-011-2201-x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 802XS UT WOS:000293544900021 PM 21660636 ER PT J AU Tani, N Joly, O Iwamuro, H Uhrig, L Wiggins, CJ Poupon, C Kolster, H Vanduffel, W Le Bihan, D Palfi, S Jarraya, B AF Tani, Naoki Joly, Olivier Iwamuro, Hirokazu Uhrig, Lynn Wiggins, Christopher J. Poupon, Cyril Kolster, Hauke Vanduffel, Wim Le Bihan, Denis Palfi, Stephane Jarraya, Bechir TI Direct visualization of non-human primate subcortical nuclei with contrast-enhanced high field MRI SO NEUROIMAGE LA English DT Article DE Subthalamic nucleus; High field; MRI; Iron oxide; Electrophysiology; Non human primate ID HUMAN SUBTHALAMIC NUCLEUS; PARKINSONS-DISEASE; MAGNETIC-SUSCEPTIBILITY; SUBSTANTIA NIGRA; GLOBUS-PALLIDUS; BRAIN IMAGES; BLOOD-VOLUME; IRON; STIMULATION; MACAQUE AB Subcortical nuclei are increasingly targeted for deep brain stimulation (DBS) and for gene transfer to treat neurological and psychiatric disorders. For a successful outcome in patients, it is critical to place DBS electrodes or infuse viral vectors accurately within targeted nuclei. However current MRI approaches are still limited to localize brainstem and basal ganglia nuclei accurately. By combining ultra-high resolution structural MRI and contrast-enhanced MRI using iron oxide nanoparticles at high field (3 T and 7 T), we could precisely locate the subcortical nuclei, in particular the subthalamic nucleus in macaques, and validate this location by intracranial electrophysiological mapping. The present data pave the way to a clinical application. (C) 2011 Elsevier Inc. All rights reserved. C1 [Jarraya, Bechir] CEA Saclay Ctr, Inserm Avenir, F-91191 Gif Sur Yvette, France. [Tani, Naoki; Joly, Olivier; Iwamuro, Hirokazu; Uhrig, Lynn; Palfi, Stephane; Jarraya, Bechir] Equipe Avenir INSERM Bettencourt Schueller, IFR49, F-91191 Gif Sur Yvette, France. [Tani, Naoki; Iwamuro, Hirokazu; Palfi, Stephane; Jarraya, Bechir] Univ Paris 12 UPEC, UF Neurochirurg Fonct Assistance Publ Hop Paris A, Grp Henri Mondor Albert Chenevier, Fac Med, F-94010 Creteil, France. [Uhrig, Lynn] Univ Paris 06, Ecole Doctorale ED3C, F-75005 Paris, France. [Kolster, Hauke; Vanduffel, Wim] Katholieke Univ Leuven, Lab Neuroen Psychofysiol, Sch Med, B-3000 Louvain, Belgium. [Vanduffel, Wim] Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02114 USA. [Vanduffel, Wim] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Jarraya, B (reprint author), CEA Saclay Ctr, Inserm Avenir, Batiment 145, F-91191 Gif Sur Yvette, France. EM bechir.jarraya@cea.fr OI Uhrig, Lynn/0000-0002-2737-0197; Jarraya, Bechir/0000-0003-0878-763X FU Inserm Avenir program; Fondation Bettencourt Schueller, Neurospin; College de France; Association pour la recherche sur la stimulation cerebrale (ARSC); Guerbet Research (Aulnay-Sous-Bois, France); KU Leuven [EF/05/014] FX This work was supported by the Inserm Avenir program, the Fondation Bettencourt Schueller, Neurospin, College de France and Association pour la recherche sur la stimulation cerebrale (ARSC). The iron oxide contrast agent P904 was kindly provided by Philippe Robert from Guerbet Research (Aulnay-Sous-Bois, France). H.K. is supported by the 'KU Leuven grant EF/05/014'. NR 62 TC 5 Z9 5 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP 1 PY 2011 VL 58 IS 1 BP 60 EP 68 DI 10.1016/j.neuroimage.2011.06.019 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 802ZC UT WOS:000293548500008 PM 21704174 ER PT J AU Cohn, N Paczynski, M Holcomb, P Jackendoff, R Kuperberg, G AF Cohn, Neil Paczynski, Martin Holcomb, Phil Jackendoff, Ray Kuperberg, Gina TI COMICS ON THE BRAIN: STRUCTURE AND MEANING IN SEQUENTIAL IMAGE COMPREHENSION SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-of-Psychophysiological-Research CY SEP 14-18, 2011 CL Boston, MA SP Soc Psychophysiol Res DE narrative; discourse; N400 C1 [Cohn, Neil; Paczynski, Martin; Holcomb, Phil; Jackendoff, Ray; Kuperberg, Gina] Tufts Univ, Medford, MA 02155 USA. [Kuperberg, Gina] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2011 VL 48 SU 1 SI SI BP S25 EP S25 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 800TE UT WOS:000293389200139 ER PT J AU Delaney-Busch, N Haime, V Wilkie, G Kuperberg, G AF Delaney-Busch, Nathaniel Haime, Vivian Wilkie, Gianna Kuperberg, Gina TI VIVID: A FULLY CROSSED ERP INVESTIGATION OF VALENCE, AROUSAL, CONCRETENESS, AND FREQUENCY SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-of-Psychophysiological-Research CY SEP 14-18, 2011 CL Boston, MA SP Soc Psychophysiol Res DE language; emotion C1 [Kuperberg, Gina] Tufts Univ, Massachusetts Gen Hosp, Medford, MA 02155 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2011 VL 48 SU 1 SI SI BP S88 EP S89 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 800TE UT WOS:000293389200496 ER PT J AU Delaney-Busch, N Kuperberg, G AF Delaney-Busch, Nathaniel Kuperberg, Gina TI LAUGH AT A FUNERAL: DISTINCT ROLES OF VALENCE CONGRUITY AND SEMANTIC CONGRUITY IN DISCOURSE SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-of-Psychophysiological-Research CY SEP 14-18, 2011 CL Boston, MA SP Soc Psychophysiol Res DE discourse; N400; emotion C1 [Delaney-Busch, Nathaniel; Kuperberg, Gina] Tufts Univ, Medford, MA 02155 USA. [Kuperberg, Gina] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2011 VL 48 SU 1 SI SI BP S42 EP S42 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 800TE UT WOS:000293389200235 ER PT J AU Fields, EC Fairbrother, WM Kuperberg, GR AF Fields, Eric C. Fairbrother, Wonja M. Kuperberg, Gina R. TI IT'S ALL ABOUT YOU: AN ERP STUDY OF THE INTERACTION OF SELF-RELEVANCE AND EMOTIONAL VALENCE IN DISCOURSE SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-of-Psychophysiological-Research CY SEP 14-18, 2011 CL Boston, MA SP Soc Psychophysiol Res DE emotion; self-relevance; language C1 [Fields, Eric C.; Fairbrother, Wonja M.; Kuperberg, Gina R.] Tufts Univ, Medford, MA 02155 USA. [Fields, Eric C.; Kuperberg, Gina R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2011 VL 48 SU 1 SI SI BP S30 EP S30 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 800TE UT WOS:000293389200166 ER PT J AU Ghorashi, S Spencer, KM AF Ghorashi, Shahab Spencer, Kevin M. TI OSCILLATORY CORRELATES OF FACE GESTALT PROCESSING IN SCHIZOPHRENIA SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-of-Psychophysiological-Research CY SEP 14-18, 2011 CL Boston, MA SP Soc Psychophysiol Res DE EEG; schizophrenia C1 [Ghorashi, Shahab; Spencer, Kevin M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2011 VL 48 SU 1 SI SI BP S44 EP S44 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 800TE UT WOS:000293389200244 ER PT J AU Kuperberg, GR Lau, E Clegg, L AF Kuperberg, Gina R. Lau, Ellen Clegg, Liam TI A GRATTON EFFECT ON THE SYNTACTIC P600: EVIDENCE THAT SYNTACTIC PROCESSING MAY BE SUBJECT TO A DYNAMIC ADJUSTMENT OF EXECUTIVE CONTROL SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 51st Annual Meeting of the Society-of-Psychophysiological-Research CY SEP 14-18, 2011 CL Boston, MA SP Soc Psychophysiol Res DE language; N400; P600 C1 [Kuperberg, Gina R.; Lau, Ellen; Clegg, Liam] Tufts Univ, Medford, MA 02155 USA. [Kuperberg, Gina R.; Lau, Ellen] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2011 VL 48 SU 1 SI SI BP S105 EP S105 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 800TE UT WOS:000293389200586 ER EF