FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fang, QQ AF Fang, Qianqian TI Mesh-based Monte Carlo method using fast ray-tracing in Plucker coordinates SO BIOMEDICAL OPTICS EXPRESS LA English DT Article AB We describe a fast mesh-based Monte Carlo (MC) photon migration algorithm for static and time-resolved imaging in 3D complex media. Compared with previous works using voxel-based media discretization, a mesh-based approach can be more accurate in modeling targets with curved boundaries or locally refined structures. We implement an efficient ray-tracing technique using Plucker Coordinates. The Barycentric coordinates computed from Plucker-formed ray-tracing enables us to use linear Lagrange basis functions to model both media properties and fluence distribution, leading to further improvement in accuracy. The Plucker-coordinate ray-polygon intersection test can be extended to hexahedral or high-order elements. Excellent agreement is found when comparing mesh-based MC with the analytical diffusion model and 3D voxel-based MC code in both homogeneous and heterogeneous cases. Realistic time-resolved imaging results are observed for a complex human brain anatomy using mesh-based MC. We also include multi-threading support in the software and will port it to a graphics processing unit platform in the near future. (C) 2010 Optical Society of America C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Fang, QQ (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM fangq@nmr.mgh.harvard.edu FU Harvard Catalyst Pilot Grant FX QF would like to thank the funding support from Harvard Catalyst Pilot Grant. He also would like to thank David Boas for the helpful discussions on the analytical diffusion solutions of a sphere. NR 39 TC 100 Z9 103 U1 0 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD AUG 2 PY 2010 VL 1 IS 1 BP 165 EP 175 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA V21LC UT WOS:000208208100016 PM 21170299 ER PT J AU Fang, QQ Moore, RH Kopans, DB Boas, DA AF Fang, Qianqian Moore, Richard H. Kopans, Daniel B. Boas, David A. TI Compositional-prior-guided image reconstruction algorithm for multi-modality imaging SO BIOMEDICAL OPTICS EXPRESS LA English DT Article AB The development of effective multi-modality imaging methods typically requires an efficient information fusion model, particularly when combining structural images with a complementary imaging modality that provides functional information. We propose a composition-based image segmentation method for X-ray digital breast tomosynthesis (DBT) and a structural-prior-guided image reconstruction for a combined DBT and diffuse optical tomography (DOT) breast imaging system. Using the 3D DBT images from 31 clinically measured healthy breasts, we create an empirical relationship between the X-ray intensities for adipose and fibroglandular tissue. We use this relationship to then segment another 58 healthy breast DBT images from 29 subjects into compositional maps of different tissue types. For each breast, we build a weighted-graph in the compositional space and construct a regularization matrix to incorporate the structural priors into a finite-element-based DOT image reconstruction. Use of the compositional priors enables us to fuse tissue anatomy into optical images with less restriction than when using a binary segmentation. This allows us to recover the image contrast captured by DOT but not by DBT. We show that it is possible to fine-tune the strength of the structural priors by changing a single regularization parameter. By estimating the optical properties for adipose and fibroglandular tissue using the proposed algorithm, we found the results are comparable or superior to those estimated with expert-segmentations, but does not involve the time-consuming manual selection of regions-of-interest. (C) 2010 Optical Society of America C1 [Fang, Qianqian; Boas, David A.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Moore, Richard H.; Kopans, Daniel B.] Massachusetts Gen Hosp, Avon Fdn Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. RP Fang, QQ (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM fangq@nmr.mgh.harvard.edu FU NIH [R01-CA97305, U54-CA105480]; Harvard Catalyst Pilot Grant FX The authors would like to thank Jayne Cormier and Donna Burgess for the assistance in the clinical experiments for this study. The authors also acknowledge the NIH funding support under grants R01-CA97305 and U54-CA105480. QF is partly supported by Harvard Catalyst Pilot Grant. NR 37 TC 17 Z9 17 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD AUG 2 PY 2010 VL 1 IS 1 BP 223 EP 235 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA V21LC UT WOS:000208208100021 PM 21258460 ER PT J AU Mesquita, RC Franceschini, MA Boas, DA AF Mesquita, Rickson C. Franceschini, Maria A. Boas, David A. TI Resting state functional connectivity of the whole head with near-infrared spectroscopy SO BIOMEDICAL OPTICS EXPRESS LA English DT Article AB Resting state connectivity aims to identify spontaneous cerebral hemodynamic fluctuations that reflect neuronal activity at rest. In this study, we investigated the spatial-temporal correlation of hemoglobin concentration signals over the whole head during the resting state. By choosing a source-detector pair as a seed, we calculated the correlation value between its time course and the time course of all other source-detector combinations, and projected them onto a topographic map. In all subjects, we found robust spatial interactions in agreement with previous fMRI and NIRS findings. Strong correlations between the two opposite hemispheres were seen for both sensorimotor and visual cortices. Correlations in the prefrontal cortex were more heterogeneous and dependent on the hemodynamic contrast. HbT provided robust, well defined maps, suggesting that this contrast may be used to better localize functional connectivity. The effects of global systemic physiology were also investigated, particularly low frequency blood pressure oscillations which give rise to broad regions of high correlation and mislead interpretation of the results. These results confirm the feasibility of using functional connectivity with optical methods during the resting state, and validate its use to investigate cortical interactions across the whole head. (C) 2010 Optical Society of America C1 [Mesquita, Rickson C.; Franceschini, Maria A.; Boas, David A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mesquita, Rickson C.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. RP Mesquita, RC (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM rickson@nmr.mgh.harvard.edu RI Mesquita, Rickson/N-9119-2013 OI Mesquita, Rickson/0000-0003-1945-6713 FU CNPq [140273/2005-0]; CAPES [2860/06-6]; National Institutes of Health [R01-EB006385, R01-EB001954, P41-RR14075] FX RCM acknowledges funding from CNPq and CAPES agencies through 140273/2005-0 and 2860/06-6, respectively. We would like to thank Christiana Andre, and Shalini Nadgir for the help collecting these data. This work was supported by the National Institutes of Health through R01-EB006385, R01-EB001954, and P41-RR14075. NR 52 TC 64 Z9 65 U1 1 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD AUG 2 PY 2010 VL 1 IS 1 BP 324 EP 336 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA V21LC UT WOS:000208208100031 PM 21258470 ER PT J AU Cui, XQ Ren, JA Tearney, GJ Yang, CH AF Cui, Xiquan Ren, Jian Tearney, Guillermo J. Yang, Changhuei TI Wavefront image sensor chip SO OPTICS EXPRESS LA English DT Article ID PHASE MICROSCOPY; CONTRAST; VISUALIZATION AB We report the implementation of an image sensor chip, termed wavefront image sensor chip (WIS), that can measure both intensity/amplitude and phase front variations of a light wave separately and quantitatively. By monitoring the tightly confined transmitted light spots through a circular aperture grid in a high Fresnel number regime, we can measure both intensity and phase front variations with a high sampling density (11 mu m) and high sensitivity (the sensitivity of normalized phase gradient measurement is 0.1 mrad under the typical working condition). By using WIS in a standard microscope, we can collect both bright-field (transmitted light intensity) and normalized phase gradient images. Our experiments further demonstrate that the normalized phase gradient images of polystyrene microspheres, unstained and stained starfish embryos, and strongly birefringent potato starch granules are improved versions of their corresponding differential interference contrast (DIC) microscope images in that they are artifact-free and quantitative. Besides phase microscopy, WIS can benefit machine recognition, object ranging, and texture assessment for a variety of applications. (C) 2010 Optical Society of America C1 [Cui, Xiquan; Ren, Jian; Tearney, Guillermo J.; Yang, Changhuei] CALTECH, Dept Elect Engn, Pasadena, CA 91125 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cui, XQ (reprint author), CALTECH, Dept Elect Engn, Pasadena, CA 91125 USA. EM xiquan@caltech.edu FU NNIN network; Wallace Coulter Foundation; NSF [BES-0547657]; NIH [R21EB008867] FX We are grateful for the constructive discussions with and the generous help from Professor Paul Sternberg, Professor Scott Fraser, Professor Colin J.R. Sheppard, Shan Shan Kou, Dr. Thomas Vangsness, Dr. Jigang Wu, Emily Mcdowell, Andrea Choe, Sean Pang, Guoan Zheng, Tony Wu, and Anne Sullivan. A portion of this work was done in the UCSB nanofabrication facility, part of the NSF funded NNIN network. The assistance from Caltech Kavli Nanoscience Institute, Watson cleanroom, and Aptina Imaging is much appreciated. This project is funded by the Wallace Coulter Foundation, NSF career award BES-0547657 and NIH R21EB008867. NR 24 TC 12 Z9 12 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD AUG 2 PY 2010 VL 18 IS 16 BP 16685 EP 16701 DI 10.1364/OE.18.016685 PG 17 WC Optics SC Optics GA 640IB UT WOS:000281042400045 PM 20721059 ER PT J AU Biederman, J Wozniak, J Faraone, S Mick, E AF Biederman, J. Wozniak, J. Faraone, S. Mick, E. TI A controlled family study of children with DSM-IV bipolar-I disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Biederman, J.; Wozniak, J.; Mick, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faraone, S.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, S.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S611 EP S611 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800821 ER PT J AU Johansen, KL Smith, MW Unruh, ML Siroka, AM O'Connor, TZ Palevsky, PM AF Johansen, Kirsten L. Smith, Mark W. Unruh, Mark L. Siroka, Andrew M. O'Connor, Theresa Z. Palevsky, Paul M. CA VA NIH Acute Renal Failure Trial N TI Predictors of Health Utility among 60-Day Survivors of Acute Kidney Injury in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; LONG-TERM OUTCOMES; COGNITIVE IMPAIRMENT; REPLACEMENT THERAPY; INTENSIVE-CARE; DISEASE; DIALYSIS; BURDEN; INDEX; MORTALITY AB Background and objectives: Health-related quality of life (HRQOL) after acute kidney injury (AKI) is an area of great importance to patients. It was hypothesized that HRQOL after AKI would relate to intensity of dialysis during AKI and dialysis dependence at follow-up. Design, setting, participants, & measurements: The Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study was a multicenter, prospective, randomized trial of intensive versus less intensive renal replacement therapy in critically ill patients with AKI. Of 1124 participants, 415 survived at least 60 days and completed the Health Utilities Index (HUI), which measures 8 health attributes and calculates an overall HRQOL score, also called a utility score. How strongly pre-intensive care unit (ICU) health, severity of illness, hospital course, intensity of dialysis, and outcome were associated with 60-day HUI scores was assessed, after adjustment for demographics. Results: The overall HUI score was 0.40 +/- 0.37, indicating severely compromised health utility and was associated with only admission from home and hospital and ICU length of stay (LOS). Ambulation was better among those with a shorter hospital and ICU LOS. Better cognition was associated with dialysis independence and with fewer comorbid chronic illnesses. Emotion was associated with only hospital LOS. Pain was associated with ICU LOS. Conclusions: Health utility was low in this cohort of patients after AKI, and intensity of dialysis did not affect subsequent health utility. The effects of a lengthy hospitalization generally outweighed the effects of delayed recovery of kidney function on HRQOL after AKI. Clin J Am Soc Nephrol 5: 1366-1372, 2010. doi: 10.2215/CJN.02570310 C1 [Johansen, Kirsten L.] San Francisco VA Med Ctr, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Smith, Mark W.; Siroka, Andrew M.] VA Palo Alto Healthcare Syst, Palo Alto, CA USA. [Smith, Mark W.] Stanford Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA USA. [Unruh, Mark L.; Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [O'Connor, Theresa Z.] VA Connecticut Healthcare Syst, W Haven Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr 111J, Nephrol Sect, 4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu RI Smith, Mark/G-1522-2012; OI Smith, Mark/0000-0002-4582-9088; Palevsky, Paul/0000-0002-7334-5400 FU U.S. Department of Veterans Affairs Office of Research and Development; U.S. National Institutes of Diabetes and Digestive and Kidney Diseases [Y1-DK-3508-01] FX This study was supported by the Cooperative Studies Program of the U.S. Department of Veterans Affairs Office of Research and Development and by the U.S. National Institutes of Diabetes and Digestive and Kidney Diseases (interagency agreement Y1-DK-3508-01). This work was presented as a Free Communication at the 42nd Annual Meeting and Scientific Exposition of the American Society of Nephrology; October 27 through November 1, 2009; San Diego, CA. NR 35 TC 31 Z9 32 U1 1 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD AUG PY 2010 VL 5 IS 8 BP 1366 EP 1372 DI 10.2215/CJN.02570310 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 635WZ UT WOS:000280689600004 PM 20507953 ER PT J AU Rhee, EP Laliberte, KA Niles, JL AF Rhee, Eugene P. Laliberte, Karen A. Niles, John L. TI Rituximab as Maintenance Therapy for Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ANCA-ASSOCIATED VASCULITIS; WEGENERS-GRANULOMATOSIS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASES; MONOCLONAL-ANTIBODY; NEGATIVE PATIENTS; METHOTREXATE; EXPERIENCE; REMISSION; DEPLETION AB Background and objectives: Ongoing randomized trials seek to validate the efficacy of rituximab as an induction agent for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, no studies directly address the role of rituximab as maintenance therapy. Design, setting, participants, & measurements: This retrospective study reports the authors' experience with continuous rituximab administration in 39 patients in complete or partial remission at the time of rituximab initiation. All 39 patients had at least 1 year of follow-up, and 20 had 2 years of follow-up. Results: Disease activity, as measured by a modified Birmingham Vasculitis Activity Score, decreased from a median of 1 at baseline to 0 at 12 (P < 0.001) and 24 months (P = 0.02). Three patients experienced nonorgan-threatening flares during 708 patient-months of follow-up. Each flare occurred after at least 20 months of follow-up. The percentage of patients on cytotoxic immunosuppression decreased from 87% at baseline to 41% at 12 months (P < 0.001) and 30% at 24 months (P = 0.002). The percentage of patients on prednisone decreased from 92% at baseline to 59% at 12 months (P < 0.001) and 55% at 24 months (P = 0.02). Two patients developed late-onset neutropenia; both responded to treatment with recombinant granulocyte colony-stimulating factor. Conclusions: The successful use of continuous anti-B cell therapy in patients with AAV in complete or partial remission is reported. This extends the potential role of rituximab beyond induction to include maintenance therapy. However, more data are required regarding the delayed adverse effects of rituximab. Clin J Am Soc Nephrol 5: 1394-1400, 2010. doi: 10.2215/CJN.08821209 C1 [Rhee, Eugene P.; Laliberte, Karen A.; Niles, John L.] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Niles, JL (reprint author), Massachusetts Gen Hosp, Renal Unit, 151 Merrimac St,3rd Floor, Boston, MA 02114 USA. EM jniles@partners.org NR 34 TC 59 Z9 60 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD AUG PY 2010 VL 5 IS 8 BP 1394 EP 1400 DI 10.2215/CJN.08821209 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 635WZ UT WOS:000280689600008 PM 20498238 ER PT J AU Adler, SG Schwartz, S Williams, ME Arauz-Pacheco, C Bolton, WK Lee, T Li, DX Neff, TB Urquilla, PR Sewell, KL AF Adler, Sharon G. Schwartz, Sherwyn Williams, Mark E. Arauz-Pacheco, Carlos Bolton, Warren K. Lee, Tyson Li, Dongxia Neff, Thomas B. Urquilla, Pedro R. Sewell, K. Lea TI Phase 1 Study of Anti-CTGF Monoclonal Antibody in Patients with Diabetes and Microalbuminuria SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID TISSUE GROWTH-FACTOR; GLOMERULAR MESSENGER-RNAS; FACTOR GENE-EXPRESSION; SMOOTH-MUSCLE-CELLS; MESANGIAL CELLS; ANGIOTENSIN-II; RENAL-DISEASE; FACTOR-BETA; FACTOR EXCRETION; NEPHROPATHY AB Background and objectives: This report summarizes the first phase 1 trial treating patients with microalbuminuric diabetic kidney disease (DKD) using FG-3019, a human monoclonal antibody to connective tissue growth factor (CTGF). CTGF is critically involved in processes of progressive fibrosis, including DKD. This phase 1, open-label, dose-escalation trial evaluated safety, pharmacokinetics, and possible therapeutic effects of FG-3019 on albuminuria, proteinuria, and tubular proteins. Design, setting, participants, and measurements: Microalbuminuric subjects (n = 24) with type 2 (79%) or type 1 (21%) diabetes received 3 or 10 mg/kg FG-3019 dosed intravenously every 14 days for four doses. Albuminuria and safety follow-up were to days 62 and 365, respectively. Results: No infusion was interrupted for symptoms, although 5 of 24 subjects had mild infusion-day adverse events thought to be possibly drug-related. No subject developed anti-FG-3019 antibodies. FG-3019 clearance was lower at 10 mg/kg than at 3 mg/kg, suggesting a saturable elimination pathway. Although this study was not designed for efficacy testing, it was notable that urinary albumin/creatinine ratio (ACR) decreased significantly from mean pretreatment ACR of 48 mg/g to mean post-treatment (day 56) ACR of 20 mg/g (P = 0.027) without evidence for a dose-response relationship. Conclusions: Treatment of microalbuminuric DKD subjects using FG-3019 was well tolerated and associated with a decrease in albuminuria. The data demonstrate a saturable pathway for drug elimination, minimal infusion adverse events, and no significant drug-attributable adverse effects over the year of follow-up. Changes in albuminuria were promising but require validation in a prospective, randomized, blinded study. Clin J Am Soc Nephrol 5: 1420-1428, 2010. doi: 10.2215/CJN.09321209 C1 [Adler, Sharon G.] Los Angeles BioMed Res Inst, Div Nephrol & Hypertens, Torrance, CA 90502 USA. [Schwartz, Sherwyn] Diabet & Glandular Dis Clin, San Antonio, TX USA. [Williams, Mark E.] Joslin Clin, Renal Unit, Boston, MA USA. [Arauz-Pacheco, Carlos] Radiant Res, Dallas, TX USA. [Bolton, Warren K.] Univ Virginia, Sch Med, Div Nephrol, Charlottesville, VA 22908 USA. [Lee, Tyson; Li, Dongxia; Neff, Thomas B.; Urquilla, Pedro R.; Sewell, K. Lea] FibroGen Inc, San Francisco, CA USA. RP Adler, SG (reprint author), Los Angeles BioMed Res Inst, Div Nephrol & Hypertens, 1124 W Carson St,Bldg C1 Annex, Torrance, CA 90502 USA. EM sadler@labiomed.org FU FibroGen, Inc. FX The authors' institutional or corporate grant offices received financial support from FibroGen, Inc. for clinical trial execution, and M.W. was a consultant for a FibroGen development meeting during the trial. T.L., D.L., and T.N. are employees of FibroGen, Inc. and therefore have direct financial relationships. P.U. and L.S. are former employees of FibroGen, Inc. This was an industry-sponsored study funded by FibroGen, Inc. Employees at FibroGen performed the analyses. Upon data sharing, the manuscript was written through a process of close collaboration of all of the cited authors. NR 49 TC 86 Z9 89 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD AUG PY 2010 VL 5 IS 8 BP 1420 EP 1428 DI 10.2215/CJN.09321209 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 635WZ UT WOS:000280689600011 PM 20522536 ER PT J AU Lopez, L Wilper, AP Cervantes, MC Betancourt, JR Green, AR AF Lopez, Lenny Wilper, Andrew P. Cervantes, Marina C. Betancourt, Joseph R. Green, Alexander R. TI Racial and Sex Differences in Emergency Department Triage Assessment and Test Ordering for Chest Pain, 1997-2006 SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT 32nd Annual National Meeting of the Society-for-General-Internal-Medicine CY MAY 13-16, 2009 CL Miami, FL SP Soc Gen Internal Med (SGIM) DE chest pain; triage; coronary disease; tests; diagnosis; ethnic groups ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; UNSTABLE ANGINA-PECTORIS; CARDIAC-CATHETERIZATION; CARDIOVASCULAR PROCEDURES; INSURANCE STATUS; UNITED-STATES; RACE; DISPARITIES; MANAGEMENT AB P>Objectives: This study assessed whether sociodemographic differences exist in triage assignment and whether these differences affect initial diagnostic testing in the emergency department (ED) for patients presenting with chest pain. Methods: A nationally representative ED data sample for all adults (>= 18 years) was obtained from the National Hospital Ambulatory Health Care Survey of EDs for 1997-2006. Weighted logistic regression was used to examine the associations between race and presenting symptom, triage assignment, and test ordering, adjusting for patient and hospital characteristics. Results: Over 10 years, an estimated 78 million visits to the ED presented with a complaint of chest pain. Of those presenting with chest pain, African Americans (odds ratio [OR] = 0.70; 99% confidence interval [CI] = 0.53 to 0.92), Hispanics (OR = 0.74; 99% CI = 0.51to 0.99), Medicaid patients (OR = 0.72; 99% CI = 0.54 to 0.94), and uninsured patients (OR = 0.65; 99% CI = 0.51 to 0.84) were less likely to be triaged emergently. African Americans (OR = 0.86; 99% CI = 0.70 to 0.99), Medicaid patients (OR = 0.70; 99% CI = 0.55 to 0.88), and uninsured patients (OR = 0.70; 99% CI = 0.55 to 0.89) were less likely to have an electrocardiogram (ECG) ordered. African Americans (OR = 0.69; 99% CI = 0.49 to 0.97), Medicaid patients (OR = 0.67; 99% CI = 0.47 to 0.95), and uninsured patients (OR = 0.66; 99% CI = 0.44 to 0.96) were less likely to have cardiac enzymes ordered. Similarly, African Americans and Hispanics were less likely to have a cardiac monitor and pulse oximetry ordered, and Medicaid and uninsured patients were less likely to have a cardiac monitor ordered. Conclusions: Persistent racial, sex, and insurance differences in triage categorization and basic cardiac testing exist. Eliminating triage disparities may affect "downstream" clinical care and help eliminate observed disparities in cardiac outcomes. C1 [Lopez, Lenny; Cervantes, Marina C.; Betancourt, Joseph R.; Green, Alexander R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lopez, Lenny; Cervantes, Marina C.; Betancourt, Joseph R.; Green, Alexander R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Lopez, Lenny; Betancourt, Joseph R.; Green, Alexander R.] Harvard Univ, Sch Med, Boston, MA USA. [Lopez, Lenny] Brigham & Womens Hosp, Brigham & Womens Acad Hospitalist Program, Boston, MA 02115 USA. [Wilper, Andrew P.] Boise VA Med Ctr, Boise, ID USA. [Wilper, Andrew P.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Lopez, L (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. EM llopez1@partners.org NR 45 TC 23 Z9 23 U1 3 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 EI 1553-2712 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD AUG PY 2010 VL 17 IS 8 BP 801 EP 808 DI 10.1111/j.1553-2712.2010.00823.x PG 8 WC Emergency Medicine SC Emergency Medicine GA 632SX UT WOS:000280449500003 PM 20670316 ER PT J AU Blue, AV Mitcham, M Smith, T Raymond, J Greenberg, R AF Blue, Amy V. Mitcham, Maralynne Smith, Thomas Raymond, John Greenberg, Raymond TI Changing the Future of Health Professions: Embedding Interprofessional Education Within an Academic Health Center SO ACADEMIC MEDICINE LA English DT Article ID STUDENTS AB Institutions are increasingly considering interprofessional education (IPE) as a means to improve health care and reduce medical errors in the United States. Effective implementation of IPE within health professions education requires a strategic institutional approach to ensure longevity and sustainability. In 2007, the Medical University of South Carolina (MUSC) established Creating Collaborative Care (C(3)), an IPE initiative that takes a multifaceted approach to weaving interprofessional collaborative experiences throughout MUSC's culture to prepare students to participate in interprofessional, collaborative health care and research settings. In this article, the authors describe C(3)'s guiding conceptual foundation and student learning goals. They present its implementation framework to illustrate how C(3) is embedded within the institutional culture. It is housed in the provost's office, and an overarching implementation committee functions as a central coordinating group. Faculty members develop and implement C(3) activities across professions by contributing to four collaborating domains-curricular, extracurricular, faculty development, and health care simulation-each of which captures an IPE component. The authors provide examples of IPE activities developed by each domain to illustrate the breadth of IPE at MUSC. The authors believe that MUSC's efforts, including the conceptual foundation and implementation framework, can be generalized to other institutions intent on developing IPE within their organizational cultures. C1 [Blue, Amy V.] Med Univ S Carolina, Charleston, SC 29425 USA. [Mitcham, Maralynne] Med Univ S Carolina, Coll Hlth Profess, Div Occupat Therapy, Charleston, SC 29425 USA. [Smith, Thomas] Med Univ S Carolina, Ctr Acad Excellence, Charleston, SC 29425 USA. [Smith, Thomas] Med Univ S Carolina, Writing Ctr, Charleston, SC 29425 USA. [Raymond, John] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Blue, AV (reprint author), 45 Courtenay Dr,Suite SS448,MSC 175, Charleston, SC 29425 USA. EM blueav@musc.edu NR 25 TC 28 Z9 28 U1 2 U2 14 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 AUG PY 2010 VL 85 IS 8 BP 1290 EP 1295 DI 10.1097/ACM.0b013e3181e53e07 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 632UD UT WOS:000280453500010 PM 20671454 ER PT J AU Nappi, JJ AF Naeppi, Janne J. TI CADe Prompts and Observer Performance: A Game of Confidence SO ACADEMIC RADIOLOGY LA English DT Editorial Material ID COMPUTER-AIDED DETECTION; CT COLONOGRAPHY; TOMOGRAPHIC COLONOGRAPHY; SCREENING MAMMOGRAPHY; MASS DETECTION; READER; SYSTEM; SUPINE; CONSPICUOUSNESS; INFORMATION C1 [Naeppi, Janne J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Naeppi, Janne J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nappi, JJ (reprint author), Massachusetts Gen Hosp, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM jnappi@partners.org NR 39 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 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD AUG PY 2010 VL 17 IS 8 BP 945 EP 947 DI 10.1016/j.acra.2010.05.012 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 627IO UT WOS:000280032900001 PM 20599154 ER PT J AU Tuller, DM Bangsberg, DR Senkungu, J Ware, NC Emenyonu, N Weiser, SD AF Tuller, David M. Bangsberg, David R. Senkungu, Jude Ware, Norma C. Emenyonu, Nneka Weiser, Sheri D. TI Transportation Costs Impede Sustained Adherence and Access to HAART in a Clinic Population in Southwestern Uganda: A Qualitative Study SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; Transportation; ARVs; Adherence; Access; Uganda ID HIV ANTIRETROVIRAL THERAPY; RESOURCE-POOR SETTINGS; SUB-SAHARAN AFRICA; ART ADHERENCE; BARRIERS; AIDS; FACILITATORS; PROGRAM; CHENNAI; INDIA AB The cost of transportation for monthly clinic visits has been identified as a potential barrier to antiretroviral (ARV) adherence in sub-Saharan Africa and elsewhere, although there is limited data on this issue. We conducted open-ended interviews with 41 individuals living with HIV/AIDS and attending a clinic in Mbarara, Uganda, to understand structural barriers to ARV adherence and clinical care. Almost all respondents cited the need to locate funds for the monthly clinic visit as a constant source of stress and anxiety, and lack of money for transportation was a key factor in cases of missed doses and missed medical appointments. Participants struggled with competing demands between transport costs and other necessities such as food, housing and school fees. Our findings suggest that transportation costs can compromise both ARV adherence and access to care. Interventions that address this barrier will be important to ensure the success of ARV programs in sub-Saharan Africa. C1 [Tuller, David M.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Bangsberg, David R.; Emenyonu, Nneka] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Initiat Global Hlth, Boston, MA 02115 USA. [Senkungu, Jude] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Ware, Norma C.] Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. [Weiser, Sheri D.] Univ Calif San Francisco, San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA 94143 USA. [Weiser, Sheri D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. RP Tuller, DM (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. EM davetuller@berkeley.edu NR 27 TC 48 Z9 50 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD AUG PY 2010 VL 14 IS 4 BP 778 EP 784 DI 10.1007/s10461-009-9533-2 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 629UW UT WOS:000280226400005 ER PT J AU Reisner, SL Perkovich, B Mimiaga, MJ AF Reisner, Sari L. Perkovich, Brandon Mimiaga, Matthew J. TI A Mixed Methods Study of the Sexual Health Needs of New England Transmen Who Have Sex with Nontransgender Men SO AIDS PATIENT CARE AND STDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-MALE TRANSSEXUALS; TRANSGENDER PERSONS; HIV PREVALENCE; HIDDEN POPULATIONS; RISK BEHAVIORS; SAN-FRANCISCO; UNITED-STATES; EPIDEMIOLOGY; PREVENTION AB The sexual health of transmen-individuals born or assigned female at birth and who identify as male-remains understudied. Given the increasing rates of HIV and sexually transmitted diseases (STDs) among gay and bisexual men in the United States, understanding the sexual practices of transmen who have sex with men (TMSM) may be particularly important to promote sexual health or develop focused HIV prevention interventions. Between May and September 2009, 16 transmen who reported sexual behavior with nontransgender men completed a qualitative interview and a brief interviewer-administered survey. Interviews were conducted until redundancy in responses was achieved. Participants (mean age, 32.5, standard deviation [SD] = 11.1; 87.5% white; 75.0% "queer") perceived themselves at moderately high risk for HIV and STDs, although 43.8% reported unprotected sex with an unknown HIV serostatus nontransgender male partner in the past 12 months. The majority (62.5%) had used the Internet to meet sexual partners and "hook-up" with an anonymous nontransgender male sex partner in the past year. A lifetime STD history was reported by 37.5%; 25.0% had not been tested for HIV in the prior 2 years; 31.1% had not received gynecological care (including STD screening) in the prior 12 months. Integrating sexual health information "by and for" transgender men into other healthcare services, involving peer support, addressing mood and psychological wellbeing such as depression and anxiety, Internet-delivered information for transmen and their sexual partners, and training for health care providers were seen as important aspects of HIV and STD prevention intervention design and delivery for this population. "Embodied scripting" is proposed as a theoretical framework to understand sexual health among transgender populations and examining transgender sexual health from a life course perspective is suggested. C1 [Reisner, Sari L.; Perkovich, Brandon; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA 02215 USA. [Reisner, Sari L.; Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Perkovich, Brandon] Harvard Univ, Cambridge, MA USA. [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Reisner, SL (reprint author), Fenway Hlth, Fenway Inst, 1340 Boylston St,8th Floor, Boston, MA 02215 USA. EM sreisner@fenwayhealth.org FU National Institute of Child Health and Human Development (NICHD) [R21HD051178]; National Institute on Drug Abuse (NIDA) [R03DA023393]; Center for Population Research in LGBT Health at The Fenway Institute FX The project described was supported by The Center for Population Research in LGBT Health at The Fenway Institute and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) under Award Number R21HD051178 (PI: J. Bradford). Some of the investigator time on this project was also support by grant number R03DA023393 from the National Institute on Drug Abuse (NIDA; PI: M. Mimiaga). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD, NIDA, or the National Institutes of Health. NR 60 TC 26 Z9 26 U1 3 U2 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD AUG PY 2010 VL 24 IS 8 BP 501 EP 513 DI 10.1089/apc.2010.0059 PG 13 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 639EW UT WOS:000280955000006 PM 20666586 ER PT J AU Gubner, NR Wilhelm, CJ Phillips, TJ Mitchell, SH AF Gubner, Noah R. Wilhelm, Clare J. Phillips, Tamara J. Mitchell, Suzanne H. TI Strain Differences in Behavioral Inhibition in a Go/No-go Task Demonstrated Using 15 Inbred Mouse Strains SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Impulsivity; Inhibition; Mice; Inbred Strains; Heritability; Go; No-go; Locomotion; Ethanol ID GENETIC-DETERMINANTS; ETHANOL WITHDRAWAL; IMPULSIVE BEHAVIOR; MICE; CONSUMPTION; SENSITIZATION; RESPONSES; SEVERITY; DRINKING; RATS AB Background: High levels of impulsivity have been associated with a number of substance abuse disorders including alcohol abuse. Research has not yet revealed whether these high levels predate the development of alcohol abuse. Methods: The current study examined impulsivity in 15 inbred strains of mice (A/HeJ, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C57L/J, C58/J, CBA/J, DBA/1J, DBA/2J, NZB/B1NJ, PL/J, SJL/J, SWR/J, and 129P3/J) using a Go/No-go task, which was designed to measure a subject's ability to inhibit a behavior. Numerous aspects of response to ethanol and other drugs of abuse have been examined in these strains. Results: There were significant strain differences in the number of responses made during the No-go signal (false alarms) and the extent to which strains responded differentially during the Go and No-go signals (d'). The rate of responding prior to the cue did not differ among strains, although there was a statistically significant correlation between false alarms and precue responding that was not related to basal activity level. Interstrain correlations suggested that false alarms and rate of responding were associated with strain differences in ethanol-related traits from the published literature. Conclusions: The results of this study do support a link between innate level of impulsivity and response to ethanol and are consistent with a genetic basis for some measures of behavioral inhibition. C1 [Gubner, Noah R.; Wilhelm, Clare J.; Phillips, Tamara J.; Mitchell, Suzanne H.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Phillips, Tamara J.; Mitchell, Suzanne H.] Portland Alcohol Res Ctr, Portland, OR USA. [Phillips, Tamara J.] Portland VA Med Ctr, Portland, OR USA. RP Mitchell, SH (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci L470, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM mitchesu@ohsu.edu OI Mitchell, Suzanne/0000-0002-0225-7200 FU The Portland Alcohol Research Center (PARC); Department of Veterans Affairs; [P60AA010760] FX We wish to thank John Crabbe, Pam Metten, and Andy Cameron for help analyzing the genetic correlation data. The authors also thank William Guethlein, Vanessa Wilson, Kirigin Elstad, and Carly Levine for technical assistance. This research was supported by The Portland Alcohol Research Center (PARC), P60AA010760 and the Department of Veterans Affairs. NR 33 TC 26 Z9 26 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2010 VL 34 IS 8 BP 1353 EP 1362 DI 10.1111/j.1530-0277.2010.01219.x PG 10 WC Substance Abuse SC Substance Abuse GA 629KA UT WOS:000280195200006 PM 20491731 ER PT J AU Cury, RC Magalhaes, TA Borges, AC Shiozaki, AA Lemos, PA Soares, J Meneghetti, JC Cury, RC Rochitte, CE AF Cury, Roberto C. Magalhaes, Tiago A. Borges, Anna C. Shiozaki, Afonso A. Lemos, Pedro A. Soares Junior, Jose Meneghetti, Jose Claudio Cury, Ricardo C. Rochitte, Carlos E. TI Dipyridamole Stress and Rest Myocardial Perfusion by 64-Detector Row Computed Tomography in Patients With Suspected Coronary Artery Disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DIAGNOSTIC-ACCURACY; ADENOSINE STRESS; CT ANGIOGRAPHY; 64-ROW; HEART AB Recently, stress myocardial computed tomographic perfusion (CTP) was shown to detect myocardial ischemia. Our main objective was to evaluate the feasibility of dipyridamole stress CTP and compare it to single-photon emission computed tomography (SPECT) to detect significant coronary stenosis using invasive conventional coronary angiography (CCA; stenosis >70%) as the reference method. Thirty-six patients (62 +/- 8 years old, 20 men) with previous positive results with SPECT (<2 months) as the primary inclusion criterion and suspected coronary artery disease underwent a customized multidetector-row CT protocol with myocardial perfusion evaluation at rest and during stress and coronary CT angiography (CTA). Multidetector-row computed tomography was performed in a 64-slice scanner with dipyridamole stress perfusion acquisition before a second perfusion/CT angiographic acquisition at rest. Independent blinded observers performed analysis of images from CTP, CTA, and CCA. All 36 patients completed the CT protocol with no adverse events (mean radiation dose 14.7 +/- 3.0 mSv) and with interpretable scans. CTP results were positive in 27 of 36 patients (75%). From the 9 (25%) disagreements, 6 patients had normal coronary arteries and 2 had no significant stenosis (8 false-positive results with SPECT, 22%). The remaining patient had an occluded artery with collateral flow confirmed by conventional coronary angiogram. Good agreement was demonstrated between CTP and SPECT on a per-patient analysis (kappa 0.53). In 26 patients using CCA as reference, sensitivity, specificity, and positive and negative predictive values were 88.0%, 79.3%, 66.7%, and 93.3% for CTP and 68.8, 76.1%, 66.7%, and 77.8%, for SPECT, respectively (p = NS). In conclusion, dipyridamole CT myocardial perfusion at rest and during stress is feasible and results are similar to single-photon emission CT scintigraphy. The anatomical-perfusion information provided by this combined CT protocol may allow identification of false-positive results by SPECT. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:310-315) C1 [Cury, Roberto C.; Magalhaes, Tiago A.; Shiozaki, Afonso A.; Rochitte, Carlos E.] Univ Sao Paulo Med, Heart Inst InCor, Cardiovasc MR & CT Sect, Sao Paulo, Brazil. [Borges, Anna C.; Soares Junior, Jose; Meneghetti, Jose Claudio] Univ Sao Paulo Med, Heart Inst InCor, Nucl Imaging Sect, Sao Paulo, Brazil. [Lemos, Pedro A.] Univ Sao Paulo Med, Heart Inst InCor, Invas Cardiol Sect, Sao Paulo, Brazil. [Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Cardiovasc MR & CT Program, Miami, FL USA. [Cury, Ricardo C.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Cury, Ricardo C.] Harvard Univ, Sch Med, Boston, MA USA. RP Rochitte, CE (reprint author), Univ Sao Paulo Med, Heart Inst InCor, Cardiovasc MR & CT Sect, Sao Paulo, Brazil. EM rochitte@incor.usp.br RI Lemos, Pedro/G-5758-2013 OI Lemos, Pedro/0000-0002-6782-750X FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Sao Paulo/Brazil [2007/56214-8]; Zerbini Foundation, Sao Paulo/Brazil FX This work was supported by Grant-in-Aid 2007/56214-8 from the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Sao Paulo/Brazil, and the Zerbini Foundation, Sao Paulo/Brazil. NR 17 TC 73 Z9 80 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 2010 VL 106 IS 3 BP 310 EP 315 DI 10.1016/j.amjcard.2010.03.025 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 635ZS UT WOS:000280697700003 PM 20643238 ER PT J AU Sun, B Williams, JS Svetkey, LP Kolatkar, NS Conlin, PR AF Sun, Bei Williams, Jonathan S. Svetkey, Laura P. Kolatkar, Nikheel S. Conlin, Paul R. TI beta(2)-Adrenergic receptor genotype affects the renin-angiotensin-aldosterone system response to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID BLOOD-PRESSURE RESPONSE; CLINICAL-TRIAL; POLYMORPHISM; LINKAGE; HUMANS; SODIUM; SUSCEPTIBILITY; ISOPROTERENOL; VASODILATION; ASSOCIATION AB Background: beta(2)-Adrenergic receptor (beta(2)-AR) is a susceptibility locus for hypertension, and polymorphisms at this site relate to salt sensitivity and low plasma renin activity (PRA). The Dietary Approaches to Stop Hypertension (DASH) dietary pattern lowers blood pressure and appears to interact with the renin-angiotensin-aldosterone system (RAAS). Objective: We hypothesized that the DASH diet associates with increased RAAS activity, and genotype status at beta(2)-AR G46A modifies this response. Design: We genotyped participants in the DASH-Sodium study (n = 372) at beta(2)-AR G46A to determine the association with blood pressure, RAAS components, and consumption of the DASH diet. We used 2-way mixed linear regression and an additive model for all primary analyses. Results: Mean (+/-SEM) PRA was significantly higher in participants in the DASH group than in participants in the control group (0.68 +/- 0.03 compared with 0.54 +/- 0.03 ng . mL(-1) . h(-1), P = 0.002). Serum aldosterone, urinary aldosterone, and urinary potassium concentrations were also significantly higher in the DASH group (P, 0.01 for all). We observed significant gene-diet interactions for changes in systolic blood pressure (SBP) and concentrations of aldosterone and urinary potassium (P for interaction = 0.048, 0.017, and 0.001 for SBP and aldosterone and urinary potassium concentrations, respectively). There was an association between the A allele of beta(2)-AR G46A and greater blood pressure reduction and blunted aldosterone and PRA responses to the DASH diet. Conclusions: Our results indicate that the DASH diet lowers blood pressure and increases PRA and aldosterone concentrations. There is an association between the G46A polymorphism of beta(2)-AR and blood pressure and RAAS responses to the DASH diet, which suggests that beta(2)-AR may be a genetic modifier of DASH-diet responsiveness. This trial was registered at clinicaltrials.gov as NCT00000608. Am J Clin Nutr 2010; 92:444-9. C1 [Sun, Bei; Williams, Jonathan S.; Conlin, Paul R.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Sun, Bei; Williams, Jonathan S.; Conlin, Paul R.] Harvard Univ, Sch Med, Boston, MA USA. [Svetkey, Laura P.] Duke Univ, Med Ctr, Duke Hypertens Ctr, Durham, NC USA. [Kolatkar, Nikheel S.] GlaxoSmithKline Res & Dev Ltd, Cardiovasc Metab Med Dev Ctr, King Of Prussia, PA USA. [Kolatkar, Nikheel S.] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Conlin, Paul R.] VA Boston Healthcare Syst, Boston, MA USA. RP Williams, JS (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM jwilliams5@partners.org OI Williams, Jonathan/0000-0001-7152-765X FU National Institutes of Health [R01 HL57114, R01 HL77234, K24 DK63214, K23 HL084236] FX Supported by grants R01 HL57114, R01 HL77234, K24 DK63214, and K23 HL084236 from the National Institutes of Health. NR 29 TC 12 Z9 12 U1 0 U2 2 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2010 VL 92 IS 2 BP 444 EP 449 DI 10.3945/ajcn.2009.28924 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 628UZ UT WOS:000280149700025 PM 20519561 ER PT J AU Zeliadt, SB Ramsey, SD Van Den Eeden, SK Hamilton, AS Oakley-Girvan, I Penson, DF Fairweather, ME Arora, NK Potosky, AL AF Zeliadt, Steven B. Ramsey, Scott D. Van Den Eeden, Stephen K. Hamilton, Ann S. Oakley-Girvan, Ingrid Penson, David F. Fairweather, Megan E. Arora, Neeraj K. Potosky, Arnold L. TI Patient Recruitment Methods to Evaluate Treatment Decision Making for Localized Prostate Cancer SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE prostate cancer; decision making; recruitment; registry ID BREAST-CANCER; STRATEGIES; MANAGEMENT; TRIAL; MEN; SURVEILLANCE; CARCINOMA AB Objective: To examine methods for identifying and recruiting prostate cancer patients prior to initiating treatment to gain insight into the treatment decision process and avoid recall bias. Study Design and Setting: One recruitment strategy involved providers and nursing staff approaching patients in community and academic urology clinics. The second recruitment strategy used electronic pathology reports to identify newly diagnosed cases in real time in an integrated health system. Our recruitment goal was to have patients complete the survey about the decision-making process prior to initiating therapy. Results: The two recruitment methods yielded different response rates. Of the 226 eligible participants approached in urology clinics, 187 (83%) returned a completed baseline survey. Of the 1177 surveys mailed to potentially eligible participants at KPNC, 617 (52%) returned a completed baseline survey. The number of surveys completed prior to treatment was 125 (67%) for the clinic recruitment approach and 437 (71%) for the electronic medical record approach. Younger participants and patients with less aggressive clinical characteristics were more likely to complete the survey before initiating treatment. Other patient demographic and clinical factors were not associated with the timing of survey return. Conclusions: Recruiting newly diagnosed patients prior to initiating treatment is feasible with both approach methods. The use of electronic medical records to identify subjects was more cost efficient, although it results in a lower response rate. C1 [Zeliadt, Steven B.; Ramsey, Scott D.; Fairweather, Megan E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Zeliadt, Steven B.] VA Puget Sound Hlth Care Syst, Hlth Serv Res, Seattle, WA USA. [Zeliadt, Steven B.] VA Puget Sound Hlth Care Syst, Dev Ctr Excellence, Seattle, WA USA. [Van Den Eeden, Stephen K.] Kaiser Permanente, Div Res, Oakland, CA USA. [Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Oakley-Girvan, Ingrid] No Calif Canc Ctr, Fremont, CA USA. [Penson, David F.] Vanderbilt Univ, Med Ctr, Vanderbilt Inst Med & Publ Hlth, Nashville, TN USA. [Arora, Neeraj K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Potosky, Arnold L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,Box 19024,M3-B232, Seattle, WA 98109 USA. EM sramsey@fhcrc.org FU National Cancer Institute [N01-PC-35142, N01-PC-35139, N01-PC-35136] FX Supported by the National Cancer Institute contracts: N01-PC-35142, N01-PC-35139, and N01-PC-35136. NR 33 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 EI 1537-453X J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD AUG PY 2010 VL 33 IS 4 BP 381 EP 386 DI 10.1097/COC.0b013e3181b215d5 PG 6 WC Oncology SC Oncology GA 635OX UT WOS:000280666200011 PM 20010079 ER PT J AU Martin, MA Hallmark, KC Sharkey, FE AF Martin, Matthew A. Hallmark, Kelly C. Sharkey, Francis E. TI Periodic Review of Pathology Training Program Teaching Files A Quality Improvement Study SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Pathology resident education; Quality improvement; Teaching file ID SURGICAL PATHOLOGY; ASSURANCE AB Pathology training programs typically retain teaching files of classic and unusual diagnostic cases. Since diagnostic criteria and terminology are mutable, we reviewed a surgical pathology teaching archive to determine if the materials continued to be acceptable for educational purposes. Each case (from 2001-2003) consisted of 1 to 3 slides and a 3 x 5 card with clinical information and the diagnosis. Cases were reviewed at a daily faculty consensus conference and categorized as follows: no diagnostic change; diagnosis added; or changed diagnosis. Slides were entirely missing from 79 (35.0%) of the 226 cases reviewed. Of the remaining 147 cases, 28 (19.0%) required additional clinical information and/or slides. The final disposition of the 147 cases was as follows: diagnosis unchanged, 126 (85.7%); diagnosis added, 15 (10.2%); and diagnosis changed, 6 (4.1%). Teaching files should be subject to prospective and retrospective controls to preserve the quality of the educational experience. C1 [Martin, Matthew A.; Sharkey, Francis E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Hallmark, Kelly C.] Audie L Murphy Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, San Antonio, TX USA. RP Sharkey, FE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 2010 VL 134 IS 2 BP 332 EP 334 DI 10.1309/AJCPKXBOAK5PMI8G PG 3 WC Pathology SC Pathology GA 627UE UT WOS:000280067600022 PM 20660339 ER PT J AU Schiavetti, R Garcia-Godoy, F Toledano, M Mazzitelli, C Barlattani, A Ferrari, M Osorio, R AF Schiavetti, Remo Garcia-Godoy, Franklin Toledano, Manuel Mazzitelli, Claudia Barlattani, Alberto Ferrari, Marco Osorio, Raquel TI Comparison of fracture resistance of bonded glass fiber posts at different lengths SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID ENDODONTICALLY TREATED TEETH; FINITE-ELEMENT-ANALYSIS; 3-POINT BENDING TEST; ROOT-CANAL POSTS; PULPLESS TEETH; STRESS-DISTRIBUTION; SEM EVALUATION; RESIN; RESTORATION; RETENTION AB Purpose To evaluate in vitro the fracture resistance of quartz fiber posts for three different dowel lengths Methods 30 single-rooted human premolars with similar root length and diameter were endodontically treated and randomly divided into three experimental groups (n=10) according to the post space depth created (1) 5 mm, (2) 7 mm, (3) 9 mm Quartz fiber posts (Endo Light post) were cemented using a dual cured resin cement with its adhesive system (Prime&Bond NT + Fluorocore 2) After 24 hours, specimens were embedded in acrylic resin and loaded under continuous compressive force at the extruding coronal part of the post (45-degree angle) to the long tooth axis (cross-head speed 0 75 mm/minute) Forces at fracture (Newtons) were recorded One-way ANOVA and Tukey tests were used for the statistical analysis (P< 0 05) Results Mean strength values (SD) were (1) 40 52 (3 14), (2) 41 68 (5 31), (3) 44 88 (6 77), respectively No statistically significant differences were found among the groups (Am J Dent 2010,23 227-230) C1 [Schiavetti, Remo; Mazzitelli, Claudia; Ferrari, Marco] Univ Siena, Dept Fixed Prosthodont & Restorat Dent, I-53100 Siena, Italy. [Garcia-Godoy, Franklin] Univ Tennessee, Hlth Sci Ctr, Res Coll Dent, Memphis, TN USA. [Garcia-Godoy, Franklin] Univ Memphis, Dept Biomed Engn, Memphis, TN 38152 USA. [Garcia-Godoy, Franklin] Forsyth Inst, Boston, MA USA. [Osorio, Raquel] Univ Granada, Dept Dent Mat, Sch Dent, E-18071 Granada, Spain. [Barlattani, Alberto] Univ Roma Tor Vergata, Dept Fixed Prosthodont, Rome, Italy. [Ferrari, Marco] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. RP Ferrari, M (reprint author), Univ Siena, Sch Dent Med, Dept Fixed Prosthodont & Dent Mat, Policlin Le Scotte, Viale Bracci, I-53100 Siena, Italy. NR 44 TC 10 Z9 10 U1 1 U2 2 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD AUG PY 2010 VL 23 IS 4 BP 227 EP 230 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 677GH UT WOS:000283976600010 PM 21250575 ER PT J AU Piris, A Scopsi, L Clemente, C Serbelloni, FC Mihm, MC Hoang, MP AF Piris, Adriano Scopsi, Lucio Clemente, Claudio Serbelloni, Federica Cetti Mihm, Martin C., Jr. Hoang, Mai P. TI Epidermal Growth Factor Receptor Gene Status by Fluorescence In Situ Hybridization in Malignant, Atypical, and Benign Hidradenomas SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE epidermal growth factor receptor; fluorescence in situ hybridization; hidradenocarcinoma; polysomy; trisomy ID CELL LUNG-CANCER; COPY NUMBER; METASTATIC HIDRADENOCARCINOMA; PROTEIN OVEREXPRESSION; BREAST-CANCER; EGFR GENE; AMPLIFICATION; GEFITINIB; CARCINOMA; EXPRESSION AB Background: Epidermal growth factor receptor (EGFR) protein overexpression and gene amplification are important prognostic factors in various tumors and EGFR inhibitors are now available as promising chemotherapeutic agents. There is little information in the literature regarding the EGFR protein and gene status in hidradenocarcinomas which has an aggressive biologic course characterized by repeated local recurrences and systemic metastasis. We have previously reported EGFR protein overexpression in malignant, atypical, and benign hidradenomas and would like to further evaluate their gene status by fluorescence in situ hybridization. Methods: Fluorescence in situ hybridization by 2-color probe Vysis LSI EGFR SpectrumOrange/CEP 7 SpectrumGreen Probe (Abbott Molecular) and EGFR immunostain (H11, Dakocytomation) were performed in 15 malignant, 15 atypical, and 7 benign hidradenomas. Results: High polysomy and low trisomy was noted in 1 and 4 hidradenocarcinoma, respectively; however, EGFR overexpression was seen only in 1 low trisomy case. Disomy is noted in the remaining 29 cases (9 hidradenocarcinomas, 15 atypical hidradenomas, and 5 benign hidradenomas). EGFR overexpression was seen in 3/12 (25%) malignant hidradenomas, 7/15 (47%) atypical hidradenomas, and 3/5 (60%) benign hidradenomas; none of these cases demonstrated EGFR gene amplification. Conclusions: Polysomy/trisomy is more frequently seen in hidradenocarcinoma than atypical and benign hidradenomas. The role of EGFR inhibitor therapy in hidradenocarcinoma cases with protein overexpression remains unclear. Lack of correlation between the protein expression and polysomy/gene amplification suggests that molecular mechanisms other than gene amplification play a role in EGFR overexpression in malignant, atypical, and benign hidradenomas. C1 [Piris, Adriano; Mihm, Martin C., Jr.; Hoang, Mai P.] Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, Boston, MA 02114 USA. [Piris, Adriano; Mihm, Martin C., Jr.; Hoang, Mai P.] Harvard Univ, Sch Med, Boston, MA USA. [Clemente, Claudio; Serbelloni, Federica Cetti] Casa de Cura San PioX, Anat Patol, Milan, Italy. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@partners.org NR 32 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD AUG PY 2010 VL 32 IS 6 BP 586 EP 592 DI 10.1097/DAD.0b013e3181cd64f2 PG 7 WC Dermatology SC Dermatology GA 629JN UT WOS:000280192800009 PM 20534988 ER PT J AU Driver, JA Yung, R Gaziano, JM Kurth, T AF Driver, Jane A. Yung, Rachel Gaziano, J. Michael Kurth, Tobias TI Chronic Disease in Men With Newly Diagnosed Cancer: A Nested Case-Control Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aging; case-control studies; geriatrics; neoplasms; risk ID PARKINSONS-DISEASE; CARDIOVASCULAR-DISEASE; PHYSICIANS HEALTH; ALZHEIMER-DISEASE; BETA-CAROTENE; COMORBIDITY; MORTALITY; SURVIVAL; COHORT; AGE AB The authors performed a matched case-control study (1982-2007) nested in a prospective cohort of 22,071 US men to determine the prevalence of chronic diseases of aging in those with newly diagnosed cancer. They matched one control by age to each of 5,622 men who developed cancer over the 25 years of follow-up, as of the date of cancer diagnosis. A modified Charlson score was calculated that reflected comorbidities prior to the matching date, and the authors used conditional logistic regression to determine the odds ratios of various diseases. No substantial differences were found between the scores of cases and controls overall, by cancer subtype, or by age at diagnosis. Overall, men who developed cancer were less likely to have had hypercholesterolemia (odds ratio (OR) = 0.79, 95% confidence interval (CI): 0.72, 0.87) or coronary artery disease (OR = 0.85, 95% CI: 0.77, 0.96). Compared with controls, men with cancers for which there is routine screening had fewer diseases, whereas those with smoking-related cancers had more. Prostate cancer was inversely associated with both coronary artery disease (OR = 0.72, 95% CI: 0.62, 0.84) and diabetes (OR = 0.72, 95% CI: 0.58, 0.89). Overall, men who developed cancer had no more comorbidity or frequent history of chronic disease than their age-matched controls. C1 [Driver, Jane A.; Gaziano, J. Michael; Kurth, Tobias] Harvard Univ, Div Aging, Brigham & Womens Hosp, Sch Med,Dept Med, Boston, MA 02120 USA. [Gaziano, J. Michael; Kurth, Tobias] Harvard Univ, Div Prevent Med, Brigham & Womens Hosp, Sch Med,Dept Med, Boston, MA 02120 USA. [Yung, Rachel] Harvard Univ, Sch Med, Dana Farber Canc Res Inst, Dept Oncol, Boston, MA 02120 USA. [Kurth, Tobias] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02120 USA. [Driver, Jane A.] Ctr Geriatr Res Educ & Clin, Boston, MA USA. [Gaziano, J. Michael] Harvard Univ, VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res Informat Ctr, Sch Med, Boston, MA 02120 USA. [Kurth, Tobias] INSERM, Neuroepidemiol U708, Paris, France. [Kurth, Tobias] Univ Paris 06, Fac Med, Paris, France. RP Driver, JA (reprint author), Harvard Univ, Div Aging, Brigham & Womens Hosp, Sch Med,Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM jdriver@partners.org RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU Hartford Foundation's Center of Excellence in Geriatric Medicine at Harvard Medical School; Eleanor and Miles Shore/Harvard Medical School; National Cancer Institute [CA-34944, CA-40360, CA-097193]; National Heart, Lung, and Blood Institute, Bethesda, Maryland [HL-26490, HL-34595]; Hartford Foundation; Parkinson's Disease Foundation (New York, New York); Harvard Medical School; Veterans Administration (Washington, DC); Department of Veterans Affairs (Washington, DC); National Institutes of Health (Bethesda, Maryland); VeroScience LLC (Tiverton, Rhode Island); Amgen Inc. (Washington, DC); National Institutes of Health; McNeil Consumer & Specialty Pharmaceuticals (Fort Washington, Pennsylvania); Merck Co., Inc.; Wyeth Consumer Healthcare (Mountain View, California) FX This work was supported by a grant from the Hartford Foundation's Center of Excellence in Geriatric Medicine at Harvard Medical School and the Eleanor and Miles Shore/Harvard Medical School Scholars in Medicine Program. The Physicians' Health Study is supported by grants from the National Cancer Institute (CA-34944, CA-40360, and CA-097193) and grants to the National Heart, Lung, and Blood Institute (HL-26490 and HL-34595), Bethesda, Maryland.; Dr. Driver has received research grants from the Hartford Foundation, the Parkinson's Disease Foundation (New York, New York), and Harvard Medical School and is the recipient of a Career Development Award from the Veterans Administration (Washington, DC). Dr. Gaziano has received investigator-initiated research grants from the Department of Veterans Affairs (Washington, DC), National Institutes of Health (Bethesda, Maryland), VeroScience LLC (Tiverton, Rhode Island), and Amgen Inc. (Washington, DC); has served as a consultant for and has received honoraria from Bayer AG (Leverkusen, Germany); and has served as an expert witness for Merck & Co., Inc. (Whitehouse Station, New Jersey). Dr. Kurth has received investigator-initiated research funds from the National Institutes of Health, McNeil Consumer & Specialty Pharmaceuticals (Fort Washington, Pennsylvania), Merck & Co., Inc., and Wyeth Consumer Healthcare (Mountain View, California; he is a consultant to i3 Drug Safety (Minneapolis, Minnesota) and World Health Information Science Consultants, LLC (Newton, Massachusetts); and he has received honoraria from Genzyme Corporation (Cambridge, Massachusetts), Merck & Co., Inc., and Pfizer Inc. (New York, New York) for educational lectures. NR 26 TC 13 Z9 13 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 1 PY 2010 VL 172 IS 3 BP 299 EP 308 DI 10.1093/aje/kwq127 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 633UB UT WOS:000280531100008 PM 20603278 ER PT J AU Kanwal, F Barkun, A Gralnek, IM Asch, SM Kuipers, EJ Bardou, M Sung, J Enns, R Agreus, L Armstrong, D Spiegel, BMR AF Kanwal, Fasiha Barkun, Alan Gralnek, Ian M. Asch, Steven M. Kuipers, Ernst J. Bardou, Marc Sung, Joseph Enns, Robert Agreus, Lars Armstrong, David Spiegel, Brennan M. R. TI Measuring Quality of Care in Patients With Nonvariceal Upper Gastrointestinal Hemorrhage: Development of an Explicit Quality Indicator Set SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PROTON PUMP INHIBITORS; DOUBLE-BLIND TRIAL; CONSENSUS RECOMMENDATIONS; HOSPITALIZED-PATIENTS; RHEUMATOID-ARTHRITIS; PEPTIC-ULCER; ENDOSCOPY; MEDICATIONS; MANAGEMENT; INFUSION AB OBJECTIVES: With an increasing emphasis on quality in health care and recognition of inconsistencies in the management of patients with nonvariceal upper gastrointestinal hemorrhage (NVUGIH), it is critical to establish a set of explicit quality indicators (QIs) in NVUGIH. METHODS: We conducted a nine-member, multidisciplinary expert panel and followed modified Delphi methods to systematically identify a set of QIs for NVUGIH. The panel performed independent ratings of each candidate QI using a nine-point RAND appropriateness scale, then met in person and re-voted using an iterative process of discussion. The final set comprised QIs with a median RAND Appropriateness Score >= 7 and no disagreement among experts. RESULTS: Among 116 candidate QIs, the panel rated 26 as valid measures of quality care. The selected QIs cover pre-endoscopy, endoscopy, and post-endoscopy care, including diagnosis, early resuscitation, risk stratification, endoscopic care, Helicobacter pylori management, and proton pump inhibitor therapy. CONCLUSIONS: We have developed an explicit set of evidence-based QIs in NVUGIH, providing physicians and institutions with a tool to identify processes amenable to quality improvement. This tool is intended to be applicable in all institutions providing care for NVUGIH patients. C1 [Asch, Steven M.; Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Kanwal, Fasiha] St Louis Vet Adm VA, St Louis, MO USA. [Kanwal, Fasiha] St Louis Univ, St Louis, MO 63103 USA. [Barkun, Alan] McGill Univ, Montreal Gen Hosp, GI Div, Montreal, PQ H3G 1A4, Canada. [Gralnek, Ian M.] Technion Israel Inst Technol, Haifa, Israel. [Gralnek, Ian M.] Rambam Med Ctr, Haifa, Israel. [Asch, Steven M.; Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kuipers, Ernst J.] Erasmus MC, Rotterdam, Netherlands. [Bardou, Marc] Univ Burgundy, Fac Med, Dijon, France. [Sung, Joseph] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Enns, Robert] Univ British Columbia, St Pauls Hosp, Vancouver, BC V5Z 1M9, Canada. [Agreus, Lars] Karolinska Inst, Stockholm, Sweden. [Armstrong, David] McMaster Univ, Hamilton, ON, Canada. RP Spiegel, BMR (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu RI Hossain, Sarah /C-7332-2009 OI Hossain, Sarah /0000-0003-1355-0979 FU Canadian Association of Gastroenterology; European Association for Gastroenterology and Endoscopy; Asian Pacific Society of Digestive Endoscopy; Canadian Institutes of Health Research (Institute of Diabetes, Metabolism and Nutrition); AstraZeneca Molndal; Abbott Canada; Olympus Canada FX Canadian Association of Gastroenterology; European Association for Gastroenterology and Endoscopy; Asian Pacific Society of Digestive Endoscopy; Canadian Institutes of Health Research (Institute of Diabetes, Metabolism and Nutrition). Sponsors: AstraZeneca Molndal, Abbott Canada, Olympus Canada through individual unrestricted grants to the Canadian Association of Gastroenterology. The supporting agencies and the sponsors had no role in the conduct of the study. NR 44 TC 17 Z9 17 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 2010 VL 105 IS 8 BP 1710 EP 1718 DI 10.1038/ajg.2010.180 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 635LJ UT WOS:000280656800001 PM 20686458 ER PT J AU Ananthakrishnan, AN McGinley, EL Saeian, K AF Ananthakrishnan, Ashwin N. McGinley, Emily L. Saeian, Kia TI Length of Office Visits for Gastrointestinal Disease: Impact of Physician Specialty SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; PRIMARY-CARE PHYSICIANS; PATIENT SATISFACTION; TIME SPENT; DURATION; MANAGEMENT; ADHERENCE; IMPROVE AB OBJECTIVES: Physician-visit length is an important determinant of patient satisfaction and outcomes. Our objective was to compare visit length for gastrointestinal disorders between gastroenterologists and primary-care providers (PCPs). METHODS: From the National Ambulatory Medical Care Survey, visits to office-based physician practices between 1993 and 2004 were identified and multivariate regression was used to identify predictors of visit duration. RESULTS: There were 3135, 3391, and 3964 office visits associated with gastrointestinal disease, corresponding to 71, 140, and 180 million visits nationwide in 1993-1996, 1997-2000, and 2001-2004 respectively. Visit duration to all physicians increased from 17.3 minutes in 1993-1996 to 20.2 minutes in 2001-2004. Among gastroenterologists, visit length remained constant, from 21.0 minutes in 1993-1996 to 22.3 minutes in 2001-2004. On multivariate regression, age >50 years (1.8 minutes), new-patient encounters (7.4 minutes), and visits in 1997-2000 (2.7 minutes) and 2001-2004 (3.4 minutes) were associated with longer visit length. Encounters with gastroenterologists (3.3 minutes) were associated with longer visit duration than those with PCPs. The greatest adjusted difference in visit length between the two was seen for visits associated with constipation (5.7 minutes favoring gastroenterologists) and irritable bowel syndrome (2.4 minutes). CONCLUSIONS: There has been an overall increase in length of physician visits associated with gastrointestinal disease. Both patient and provider factors predict visit length. C1 [Ananthakrishnan, Ashwin N.; Saeian, Kia] Med Coll Wisconsin, Div Gastroenterol & Hepatol, Milwaukee, WI 53226 USA. [McGinley, Emily L.] Med Coll Wisconsin, Div Epidemiol, Milwaukee, WI 53226 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 165 Cambridge St, Boston, MA 02114 USA. EM aananthakrishnan@partners.org NR 23 TC 3 Z9 3 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 2010 VL 105 IS 8 BP 1719 EP 1725 DI 10.1038/ajg.2010.172 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 635LJ UT WOS:000280656800002 PM 20686459 ER PT J AU Dienstag, JL AF Dienstag, Jules L. TI Peginterferon Therapy for HBeAg-Negative Chronic Hepatitis B: Less Than Meets the Eye SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID BIOCHEMICAL RESPONSE; VIRUS-INFECTION; ALPHA-2A 40KD; FOLLOW-UP; LAMIVUDINE; COMBINATION; RIBAVIRIN AB Pegylated interferon (PEG IFN) has been recommended as a first-line therapy for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B; however, data supporting this recommendation are derived from a single randomized controlled trial. In this issue of the Journal, Rijckborst et al. report the results of a second randomized controlled PEG IFN trial in 138 HBeAg-negative patients. The trial was undertaken to test the efficacy of adding ribavirin to PEG IFN; however, the results were unequivocal in concluding that adding ribavirin was not effective. Moreover, the efficacy of PEG IFN for these HBeAg-negative subjects was disappointing; only 7.5% of the study cohort had undetectable hepatitis B virus DNA (<400 copies/ml) 24 weeks after a 48-week course of therapy, and none lost hepatitis B surface antigen. This study challenges the value and limits the appeal of PEG IFN therapy for HBeAg-negative chronic hepatitis B. C1 [Dienstag, Jules L.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Med Serv, Jackson 7,55 Fruit St, Boston, MA 02114 USA. EM jdienstag@partners.org NR 17 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 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 2010 VL 105 IS 8 BP 1770 EP 1772 DI 10.1038/ajg.2010.187 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 635LJ UT WOS:000280656800009 PM 20686463 ER PT J AU Stoffel, EM Mercado, RC Kohlmann, W Ford, B Grover, S Conrad, P Blanco, A Shannon, KM Powell, M Chung, DC Terdiman, J Gruber, SB Syngal, S AF Stoffel, Elena M. Mercado, Rowena C. Kohlmann, Wendy Ford, Beth Grover, Shilpa Conrad, Peggy Blanco, Amie Shannon, Kristen M. Powell, Mark Chung, Daniel C. Terdiman, Jonathan Gruber, Stephen B. Syngal, Sapna TI Prevalence and Predictors of Appropriate Colorectal Cancer Surveillance in Lynch Syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID MISMATCH-REPAIR GENES; COLON-CANCER; LONG-TERM; MICROSATELLITE INSTABILITY; BETHESDA GUIDELINES; SCREENING PRACTICES; MUTATION CARRIERS; HIGH-RISK; HNPCC; FAMILIES AB OBJECTIVES: Lynch syndrome (LS) is a hereditary cancer syndrome that conveys a high risk of colorectal cancer (CRC). Guidelines recommend colonoscopy every 1 to 2 years. There is limited information about screening compliance in this high-risk group. METHODS: Data about cancer screening behaviors were obtained from subjects recruited through four US cancer genetics clinics. The main outcome was prevalence of appropriate CRC surveillance for LS. RESULTS: A total of 181 individuals had a family history that met the Amsterdam criteria for LS (n = 154) and/or had an identified mutation in a mismatch repair (MMR) gene (n = 105). Of these 181 individuals, 131 (73%) had appropriate LS surveillance with colonoscopies at least every 2 years for their age >= 25 years. Of those with inadequate surveillance, 26/49 (53%) had colonoscopies at 3- to 5-year intervals. There were no significant differences in health-care setting, perceived risk of CRC, or compliance with screening for other cancers. Rates of appropriate surveillance were higher among individuals who had been referred for genetic evaluation for LS compared with those who had not (109/136 (80%) vs. 23/45 (51%), respectively, P = 0.0004). In multivariate analysis, personal history of CRC (odds ratio (OR) 2.81), having a first-degree relative with CRC at age <50 years (OR 2.61), and having undergone a genetic evaluation (OR 4.62) were associated with appropriate CRC surveillance for LS. CONCLUSIONS: The time between colonoscopic exams in patients with LS is often longer than recommended by current guidelines and may place them at risk for interval cancers. Recognizing clinical features of LS and providing genetic counseling, evaluation, and intensive surveillance may improve cancer prevention for those at the highest risk for CRC. C1 [Stoffel, Elena M.; Grover, Shilpa; Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Stoffel, Elena M.; Mercado, Rowena C.; Ford, Beth; Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. [Stoffel, Elena M.; Chung, Daniel C.; Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Kohlmann, Wendy; Gruber, Stephen B.] Univ Michigan, Med Ctr, Div Mol Med & Genet, Ann Arbor, MI USA. [Conrad, Peggy; Blanco, Amie; Terdiman, Jonathan] Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. [Shannon, Kristen M.; Chung, Daniel C.] Massachusetts Gen Hosp, Ctr Canc Risk Anal, Boston, MA 02114 USA. [Powell, Mark] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. RP Stoffel, EM (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. EM estoffel@partners.org OI Blanco, Amie/0000-0003-3690-0038 FU American College of Gastroenterology; GlaxoSmithKline; National Institutes of Health/National Cancer Institute [K07 NCI CA 120448-01-A2, K24 NCI CA 113433] FX This study was supported in part by the American College of Gastroenterology Junior Faculty Award (2004, Stoffel) and GlaxoSmithKline GIDH Clinical Research Award (2004, Stoffel). Stoffel is supported by the National Institutes of Health/National Cancer Institute career development award K07 NCI CA 120448-01-A2 (Stoffel) and K24 NCI CA 113433 (Syngal). NR 32 TC 23 Z9 23 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 2010 VL 105 IS 8 BP 1851 EP 1860 DI 10.1038/ajg.2010.120 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 635LJ UT WOS:000280656800021 PM 20354509 ER PT J AU Rabin, DU Kuter, DJ Liebman, HA Bussel, JB AF Rabin, Daniel U. Kuter, David J. Liebman, Howard A. Bussel, James B. TI What do healthcare providers ask their patients with immune thrombocytopenia? SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID QUALITY-OF-LIFE; PURPURA; ROMIPLOSTIM; DISEASE; ADULTS AB Clinical signs suggestive of immune thrombocytopenia (ITP) include bruising, petechiae, nose bleeds, genitourinary (GU) bleeding, gum bleeding, gastrointestinal (GI) bleeding, and gynecologic bleeding [1]. Clinical experience and adverse events in clinical trials reveal other lip-associated symptoms such as arthritis, abdominal pain, sleep disturbances, headache, and fatigue. Asking patients about such symptoms supplements the platelet count in assessing disease status and impact, and thus helps in the design of a patient-specific management plan. A short practice patterns survey was administered to healthcare providers attending ITP Continuing Medical Education (CME) activities to assess the questions they ask patients in monitoring visits. A high percentage of respondents routinely ask about signs of bleeding and associated symptoms but not as frequently about health-related quality of life (HRQOL). Only 39% of respondents ask about difficulty with sleep. A short standardized questionnaire may be a useful tool to help healthcare providers gather information about their patients with ITP. C1 [Rabin, Daniel U.] France Fdn, Old Lyme, CT 06371 USA. [Kuter, David J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol,MGH Canc Ctr, Boston, MA USA. [Liebman, Howard A.] Univ So Calif, Keck Sch Med, Jane Anne Nohl Div Hematol, Los Angeles, CA 90033 USA. [Liebman, Howard A.] Univ So Calif, Keck Sch Med, Ctr Study Blood Dis, Los Angeles, CA 90033 USA. [Bussel, James B.] Cornell Univ, Weill Med Coll, Dept Pediat Hematol Oncol, New York, NY 10021 USA. RP Rabin, DU (reprint author), France Fdn, 230 Shore Rd, Old Lyme, CT 06371 USA. EM drabin@francefoundation.com NR 10 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD AUG PY 2010 VL 85 IS 8 BP 629 EP 631 DI 10.1002/ajh.21764 PG 3 WC Hematology SC Hematology GA 634EQ UT WOS:000280562800022 PM 20658595 ER PT J AU Jagannath, AD Rastogi, U Spooner, AE Lin, AE Agnihotri, AK AF Jagannath, Anand D. Rastogi, Ujjwal Spooner, Amy E. Lin, Angela E. Agnihotri, Arvind K. TI Aortic Dissection and Moyamoya Disease in Turner Syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE aortic dilation; aortic dissection; Turner syndrome; vascular disease; vasculopathy ID DILATATION; REVASCULARIZATION; VASCULOPATHY; DYSFUNCTION; PREVALENCE; ANEURYSMS; CHILDREN; WOMEN AB Aortic dilation and dissection are well-recognized cardiac abnormalities in women with Turner syndrome (TS), although the underlying pathophysiology is not fully understood. We report on a 46-year-old Hispanic woman who was previously diagnosed with moyamoya disease on magnetic resonance imaging after a presentation with stroke-like symptoms. Her features were consistent with TS and chromosome analysis revealed mosaicism in which 17% of the cells showed a pseudoisodicentric Y chromosome: 45,X (25)146,X psu idic (Y)(11.2) (5). A preceding screening transthoracic echocardiogram had shown a bicuspid aortic valve (BAV) with an aortic diameter of 3.2 cm; at the time of moyamoya diagnosis, the aorta was 3.5 cm with mild aortic stenosis and mild aortic regurgitation. Four years later, the patient had had an acute aortic dissection, Stanford type A, which was repaired successfully. This case report is the third individual with TS associated with moyamoya disease and the first associated with dissection. The small number of cases does not allow detailed analysis other than noting patient age (two older than 40 years), karyotype (two others associated with isochrome Xq), and associated cardiac risk factors (one with BAV). Although this may be a chance occurrence, we hypothesize that moyamoya disease could be a manifestation of the vasculopathy in TS. (C) 2010 Wiley-Liss, Inc. C1 [Agnihotri, Arvind K.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. [Spooner, Amy E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA. RP Agnihotri, AK (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Cox Bldg,Room 642,55 Fruit St, Boston, MA 02114 USA. EM aagnihotri@partners.org NR 26 TC 4 Z9 4 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD AUG PY 2010 VL 152A IS 8 BP 2085 EP 2089 DI 10.1002/ajmg.a.33539 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 638VO UT WOS:000280925800032 PM 20635402 ER PT J AU Shargorodsky, J Curhan, GC Farwell, WR AF Shargorodsky, Josef Curhan, Gary C. Farwell, Wildon R. TI Prevalence and Characteristics of Tinnitus among US Adults SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Anxiety; Depression; Epidemiology; Hearing loss; Tinnitus ID HEARING-LOSS; DEPRESSION; EPIDEMIOLOGY; SUFFERERS; PATIENT; ANXIETY; TRAUMA AB BACKGROUND: Tinnitus is common; however, few risk factors for tinnitus are known. METHODS: We examined cross-sectional relations between several potential risk factors and self-reported tinnitus in 14,178 participants in the 1999-2004 National Health and Nutrition Examination Surveys, a nationally representative database. We calculated the prevalence of any and frequent (at least daily) tinnitus in the overall US population and among subgroups. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for multiple potential confounders. RESULTS: Approximately 50 million US adults reported having any tinnitus, and 16 million US adults reported having frequent tinnitus in the past year. The prevalence of frequent tinnitus increased with increasing age, peaking at 14.3% between 60 and 69 years of age. Non-Hispanic whites had higher odds of frequent tinnitus compared with other racial/ethnic groups. Hypertension and former smoking were associated with an increase in odds of frequent tinnitus. Loud leisure-time, firearm, and occupational noise exposure also were associated with increased odds of frequent tinnitus. Among participants who had an audiogram, frequent tinnitus was associated with low-mid frequency (OR 2.37; 95% CI, 1.76-3.21) and high frequency (OR 3.00; 95% CI, 1.78-5.04) hearing impairment. Among participants who were tested for mental health conditions, frequent tinnitus was associated with generalized anxiety disorder (OR 6.07; 95% CI, 2.33-15.78) but not major depressive disorder (OR 1.58; 95% CI, 0.54-4.62). CONCLUSIONS: The prevalence of frequent tinnitus is highest among older adults, non-Hispanic whites, former smokers, and adults with hypertension, hearing impairment, loud noise exposure, or generalized anxiety disorder. Prospective studies of risk factors for tinnitus are needed. Published by Elsevier Inc. The American Journal of Medicine (2010) 123, 711-718 C1 [Farwell, Wildon R.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Shargorodsky, Josef; Curhan, Gary C.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Farwell, Wildon R.] Harvard Univ, Sch Med, Boston, MA USA. [Farwell, Wildon R.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. [Shargorodsky, Josef] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Farwell, WR (reprint author), VA Boston Healthcare Syst, Boston Div 151 MAV, 150 S Huntington Ave, Boston, MA 02130 USA. EM wildon.farwell@va.gov FU Massachusetts Eye and Ear Infirmary Foundation FX This work was supported by the Massachusetts Eye and Ear Infirmary Foundation and with resources and the use of facilities at the Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System. NR 29 TC 206 Z9 218 U1 7 U2 42 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2010 VL 123 IS 8 BP 711 EP 718 DI 10.1016/j.amjmed.2010.02.015 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 631UG UT WOS:000280374200012 PM 20670725 ER PT J AU Williams, LH Rutter, CM Katon, WJ Reiber, GE Ciechanowski, P Heckbert, SR Lin, EHB Ludman, EJ Oliver, MM Young, BA Von Korff, M AF Williams, Lisa H. Rutter, Carolyn M. Katon, Wayne J. Reiber, Gayle E. Ciechanowski, Paul Heckbert, Susan R. Lin, Elizabeth H. B. Ludman, Evette J. Oliver, Malia M. Young, Bessie A. Von Korff, Michael TI Depression and Incident Diabetic Foot Ulcers: A Prospective Cohort Study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Complications; Depression; Diabetes; Foot ulcers ID PERIPHERAL ARTERIAL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; SELF-CARE; AFRICAN-AMERICANS; LEG SYMPTOMS; RISK; MORTALITY; ASSOCIATION; COMPLICATIONS; PREVENTION AB OBJECTIVE: To test whether depression is associated with an increased risk of incident diabetic foot ulcers. METHODS: The Pathways Epidemiologic Study is a population-based prospective cohort study of 4839 patients with diabetes in 2000-2007. The present analysis included 3474 adults with type 2 diabetes and no prior diabetic foot ulcers or amputations. Mean follow-up was 4.1 years. Major and minor depression assessed by the Patient Health Questionnaire-9 were the exposures of interest. The outcome of interest was incident diabetic foot ulcers. We computed the hazard ratio and 95% confidence interval (CI) for incident diabetic foot ulcers, comparing patients with major and minor depression with those without depression and adjusting for sociodemographic characteristics, medical comorbidity, glycosylated hemoglobin, diabetes duration, insulin use, number of diabetes complications, body mass index, smoking status, and foot self-care. Sensitivity analyses also adjusted for peripheral neuropathy and peripheral arterial disease as defined by diagnosis codes. RESULTS: Compared with patients without depression, patients with major depression by Patient Health Questionnaire-9 had a 2-fold increase in the risk of incident diabetic foot ulcers (adjusted hazard ratio 2.00; 95% CI, 1.24-3.25). There was no statistically significant association between minor depression by Patient Health Questionnaire-9 and incident diabetic foot ulcers (adjusted hazard ratio 1.37; 95% CI, 0.77-2.44). CONCLUSION: Major depression by Patient Health Questionnaire-9 is associated with a 2-fold higher risk of incident diabetic foot ulcers. Future studies of this association should include better measures of peripheral neuropathy and peripheral arterial disease, which are possible confounders or mediators. (C) 2010 Elsevier Inc. All rights reserved. The American Journal of Medicine (2010) 123, 748-754 C1 [Williams, Lisa H.] Univ Washington, Div Dermatol, Dept Med, Seattle, WA 98195 USA. [Rutter, Carolyn M.; Heckbert, Susan R.; Lin, Elizabeth H. B.; Ludman, Evette J.; Oliver, Malia M.; Von Korff, Michael] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Katon, Wayne J.; Ciechanowski, Paul] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Reiber, Gayle E.] Univ Washington, Hlth Serv Res & Dev Ctr Excellence, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Young, Bessie A.] Univ Washington, Epidemiol Res & Informat Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Young, Bessie A.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. RP Williams, LH (reprint author), 125 16th Ave E,Mail Stop CSB 5, Seattle, WA 98112 USA. EM lisahw@u.washington.edu FU National Institutes of Health [MH-073686]; National Institutes of Health/American Skin Association [F32 AR-056380]; Dermatology Foundation FX This research was supported by National Institutes of Health grant MH-073686. Dr Williams was supported by National Institutes of Health/American Skin Association grant F32 AR-056380 and a Dermatology Foundation Dermatologist Investigator Research Fellowship. NR 31 TC 30 Z9 34 U1 4 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2010 VL 123 IS 8 BP 748 EP U151 DI 10.1016/j.amjmed.2010.01.023 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 631UG UT WOS:000280374200017 PM 20670730 ER PT J AU Gingo, M Risbano, MG Russ, PD Chan, ED AF Gingo, Matthew Risbano, Michael G. Russ, Paul D. Chan, Edward D. TI Not Your Otitis Media 101 SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID INTRACRANIAL COMPLICATIONS C1 [Chan, Edward D.] Natl Jewish Hlth, Denver, CO 80206 USA. [Gingo, Matthew; Risbano, Michael G.; Chan, Edward D.] Univ Colorado, Dept Med, Denver, CO USA. [Gingo, Matthew; Risbano, Michael G.; Chan, Edward D.] Univ Colorado, Div Pulm Sci & Crit Care, Denver, CO USA. [Russ, Paul D.] Univ Colorado, Dept Radiol, Denver, CO USA. [Russ, Paul D.; Chan, Edward D.] Denver Vet Affairs Med Ctr, Hlth Sci Ctr, Denver, CO USA. RP Chan, ED (reprint author), Natl Jewish Hlth, K720,Goodman Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org RI Gingo, Matthew/K-7203-2013; OI Risbano, Michael/0000-0003-3334-7046 NR 5 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 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2010 VL 123 IS 8 BP E9 EP E11 DI 10.1016/j.amjmed.2009.12.038 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 631UG UT WOS:000280374200024 PM 20670714 ER PT J AU Hollander, DA Giaconi, JA Holland, GN Yu, F Caprioli, J Aldave, AJ Coleman, AL Casey, R Law, SK Mondino, BJ AF Hollander, David A. Giaconi, Joann A. Holland, Gary N. Yu, Fei Caprioli, Joseph Aldave, Anthony J. Coleman, Anne L. Casey, Richard Law, Simon K. Mondino, Bartly J. TI Graft Failure After Penetrating Keratoplasty in Eyes With Ahmed Valves SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID GLAUCOMA DRAINAGE DEVICE; ENDOTHELIAL-CELL DENSITY; RISK-FACTORS; MOLTENO IMPLANT; TUBE SHUNT; FOLLOW-UP; SURVIVAL; OUTCOMES; THERAPY AB PURPOSE: To determine incidence and risk factors for graft failure following penetrating keratoplasty (PK) in eyes with Ahmed valves (AV). DESIGN: Retrospective, observational cohort study. METHODS: Patients who underwent PK after AV implantation (both performed at our institution through 2004) were studied. Intervals to graft failure (defined as either dysfunction [stromal thickening with retention of clarity] or decompensation [central microcystic edema or loss of clarity]) were analyzed using Kaplan-Meier technique. Risk factors for graft failure were analyzed using Cox proportional hazard models. RESULTS: Included were 77 eyes (77 patients; first procedure 1993). Following PK, 40 eyes (52%) required increased numbers of glaucoma medications; 10 eyes (13%) required additional glaucoma drainage device(s). Graft failure at 1, 2, and 3 years was 42.4% (95% confidence interval: 32.0%-54.6%), 57.1% (45.6%-69.1%), and 59.1% (47.5%-71.2%), respectively. Prior PK (HR 2.38, P = .006) and stromal vessels (HR 2.90, P = .0005) were associated with increased risk of graft failure. Use of glaucoma medications (HR 0.27, P = .009) and evidence of lower intraocular pressures (IOP) during follow-up (excluding hypotony; HR 0.92, P = .010) were associated with reduced risk of graft failure. Endothelial rejection episodes were observed in 13 eyes (17%); however, rejection was not a risk factor for graft failure (P = .98). CONCLUSIONS: Long-term survival of corneal grafts is poor in eyes with AV. The majority of graft failures are associated with progressive loss of endothelial function, without observed immunologic rejection. Despite the presence of an AV, escalation in glaucoma therapy often follows PK; graft failure may be related to poor IOP control. (Am J Ophthalmol 2010;150:169-178. Published by Elsevier Inc.) C1 [Hollander, David A.; Giaconi, Joann A.; Holland, Gary N.; Yu, Fei; Caprioli, Joseph; Aldave, Anthony J.; Coleman, Anne L.; Casey, Richard; Law, Simon K.; Mondino, Bartly J.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Hollander, David A.; Giaconi, Joann A.; Holland, Gary N.; Yu, Fei; Caprioli, Joseph; Aldave, Anthony J.; Coleman, Anne L.; Casey, Richard; Law, Simon K.; Mondino, Bartly J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Hollander, David A.; Giaconi, Joann A.; Holland, Gary N.] Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. RP Giaconi, JA (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM giaconi@jsei.ucla.edu OI Caprioli, Joseph/0000-0002-2383-7263 FU HEED OPHTHALMIC FOUNDATION CLEVELAND, OHIO; Research to Prevent Blindness (RPB), Inc, New York, New York; Vernon O. Underwood Family Endowed Professorship; RPB FX PUBLICATION OF THIS STUDY WAS SUPPORTED BY THE HEED OPHTHALMIC FOUNDATION CLEVELAND, OHIO (DR HOLLANDER); Research to Prevent Blindness (RPB), Inc, New York, New York (Dr Holland); and the Vernon O. Underwood Family Endowed Professorship (Dr Holland). Dr Holland was recipient of an RPB Physician-Scientist Award. Dr Hollander is currently an employee of Allergan, Inc. Funding entities had no role in the conduction or presentation of this study. Involved in study design (D.A.H., J.A.G., G.N.H., F.Y.); data collection (D.A.H., JAG., G.N.H., J.C., A.J.A., A.L.C., R.C., S.K.L., B.J.M.); data management and analysis (D.A.H., JAG., G.N.H., F.Y.); data interpretation (D.A.H., JAG., G.N.H., F.Y., J.C., A.J.A., A.L.C., B.J.M.); preparation of initial draft of manuscript (D.A.H., JAG., G.N.H., F.Y.); and review and approval of manuscript (D.A.H., JAG., G.N.H., F.Y., J.C., A.J.A., A.L.C., R.C., S.K.L., B.J.M.). D. Hollander and J. Giaconi contributed equally to the preparation of this article. This study was approved by the Institutional Review Board at UCLA. NR 26 TC 24 Z9 24 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 AUG PY 2010 VL 150 IS 2 BP 169 EP 178 DI 10.1016/j.ajo.2010.02.014 PG 10 WC Ophthalmology SC Ophthalmology GA 635ZT UT WOS:000280697800006 PM 20537311 ER PT J AU Kohno, RI Hata, Y Mochizuki, Y Arita, R Kawahara, S Kita, T Miyazaki, M Hisatomi, T Ikeda, Y Aiello, LP Ishibashi, T AF Kohno, Ri-Ichiro Hata, Yasuaki Mochizuki, Yasutaka Arita, Ryoichi Kawahara, Shuhei Kita, Takeshi Miyazaki, Masanori Hisatomi, Toshio Ikeda, Yasuhiro Aiello, Lloyd Paul Ishibashi, Tatsuro TI Histopathology of Neovascular Tissue From Eyes With Proliferative Diabetic Retinopathy After Intravitreal Bevacizumab Injection SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RETINAL VEIN OCCLUSION; MACULAR DEGENERATION; PRIMATE EYE; AVASTIN; GLAUCOMA; MONKEY AB PURPOSE: To examine the histopathologic effect of a single intravitreal injection of bevacizumab on newly formed vessels in eyes with proliferative diabetic retinopathy (PDR). DESIGN: Interventional case series and laboratory investigation. METHODS: Two days after intravitreal injection of bevacizumab (1.25 mg/eye), pars plana vitrectomy or trabeculectomy was performed for the treatment of PDR or neovascular glaucoma (NVG) associated with PDR. Ten surgically removed preretinal proliferative tissues and 6 deep scleral flaps containing trabecular meshwork were fixed in 2% glutaraldehyde or 4% paraformaldehyde and were subjected to transmission electron microscopic analysis, immunohistochemical analysis, and terminal deoxyuridiine triphosphate (dUTP) nick-end labeling staining. Two surgically removed preretinal proliferative tissues and 2 deep scleral flaps from patients with PDR and NVG, but without preoperative intravitreal injection of bevacizumab (IVB), served as controls. RESULTS: In control tissues, vascular endothelial cells possessed many fenestrations and were accompanied by pericytes. Apoptotic vascular endothelial cells frequently were observed in tissue after intravitreal injection of bevacizumab, whereas they were not observed in control tissues. Additionally, no apparent fenestration was observed in newly formed vessels from either proliferative tissue or trabecular meshwork after intravitreal injection of bevacizumab. In both PDR and NVG tissues after intravitreal injection of bevacizumab, overexpression of smooth muscle actin was observed in newly formed vessels, suggesting that the treatment may have increased pericytes on the vasculature as compared with control tissue. CONCLUSIONS: Intravitreal injection of bevacizumab may induce changes in immature, newly formed vessels of PDR or NVG tissue, leading to endothelial apoptosis with vascular regression, while inducing normalization of premature vessels by increasing pericyte coverage and reducing vessel fenestration. (Am J Ophthalmol 2010;150:223-229. (C) 2010 by Elsevier Inc. All rights reserved.) C1 [Hata, Yasuaki] Fukuoka Dent Coll, Dept Med, Sect Ophthalmol, Sawara Ku, Fukuoka 8140193, Japan. [Kohno, Ri-Ichiro; Mochizuki, Yasutaka; Arita, Ryoichi; Kawahara, Shuhei; Kita, Takeshi; Miyazaki, Masanori; Hisatomi, Toshio; Ikeda, Yasuhiro; Ishibashi, Tatsuro] Kyushu Univ, Dept Ophthalmol, Grad Sch Med Sci, Fukuoka 812, Japan. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02115 USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Hata, Y (reprint author), Fukuoka Dent Coll, Dept Med, Sect Ophthalmol, Sawara Ku, 2-15-1 Tamura, Fukuoka 8140193, Japan. EM hatachan@med.kyushu-u.ac.jp OI Hisatomi, Toshio/0000-0003-2552-9595 FU Ministry of Education, Science, Sports and Culture, Tokyo, Japan [21592233] FX PUBLICATION OF THIS STUDY IS SUPPORTED IN PART BY GRANT-IN-AID FOR SCIENTIFIC RESEARCH 21592233 FROM THE Ministry of Education, Science, Sports and Culture, Tokyo, Japan. The authors indicate no financial conflict of interest. Involved in design of study (R.I., Y.H., L.P.A., T.I.); Conduct of study (RA., S.K., T.H.); Data collection (R.K., Y.H., Y.M., MM.); Provision of material (Y.H., Y.M., RA., S.K., M.M., T.H., Y.I.); Analysis of data (R.A., S.K., T.H.); Statistical experience (R.A., S.K., T.K.); Obtaining funding (R.I., Y.H., Y.M., R.A., S.K., T.K., MM., T.H., Y.I., T.I.); Literature search (R.I., R.A., S.K., T.K.); Administrative support (Y.H., L.P.A.); Writing the article (R.I., Y.H., L.P.A.); Critical revision (Y.H., Y.M., R.A., S.K., T.K., M.M., T.H., Y.I., L.P.P., T.I.); and Final approval (R.I., Y.H., Y.M., R.A., S.K., T.K., MM., T.H., Y.I., L.P.P., T.I.). This study was carried out with approval from the Institutional Review Board at Kyushu University Hospital and was performed in accordance with the ethical standards of the 1989 Declaration of Helsinki. Written informed consent was obtained from all 15 patients. NR 23 TC 21 Z9 25 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 AUG PY 2010 VL 150 IS 2 BP 223 EP 229 DI 10.1016/j.ajo.2010.03.016 PG 7 WC Ophthalmology SC Ophthalmology GA 635ZT UT WOS:000280697800014 PM 20542485 ER PT J AU Jakobiec, FA Bhat, P AF Jakobiec, Frederick A. Bhat, Pooja TI Retrocorneal Membranes: A Comparative Immunohistochemical Analysis of Keratocytic, Endothelial, and Epithelial Origins SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CORNEAL ENDOTHELIUM; PERFORATING INJURY; GROWTH-FACTOR; DYSTROPHY; CELLS; PROLIFERATION; KERATOPLASTY; CYTOKERATINS; EXPRESSION; FEATURES AB PURPOSE: To determine through the use of immunohistochemistry the origins of retrocorneal cellular and fibrillar membranes. DESIGN: Retrospective, clinicopathologic study using surgically removed human corneal tissues. METHODS: Clinical records of patients' ocular diseases and surgical procedures were reviewed. Immunohistochemical staining was performed on 5 enucleated control globes, 32 penetrating keratoplasty specimens, and 6 Descemet stripping endothelial keratoplasty specimens to analyze: (1) the normal corneal epithelium, stroma, and endothelium; and (2) stromal scars, endothelial abnormalities, and retrocorneal membranes. Paraffin sections were stained with hematoxylin and eosin, periodic acid-Schiff, and Masson trichrome methods, and immunohistochemical analyses were performed with commonly available monoclonal and polyclonal antibodies for various cytokeratins (CKs), CD34, alpha-smooth muscle actin (SMA), and vimentin. RESULTS: Five subtypes among 28 retrocorneal membranes were characterized. Twelve fibrous (keratocytic) membranes of stromal origin had coarse collagen and immunostained negatively for all CKs, but strongly for vimentin and alpha-SMA, the last the only marker of diagnostic value. Nine metaplastic endothelium-derived membranes produced delicate collagenous matrices and immunoreacted with CK7, vimentin, and alpha-SMA. Two epithelial multilaminar or monolaminar membranes reacted with CK cocktail and wide-spectrum CK, mildly with CK7 (not observed in orthotopic surface epithelium), and negatively for alpha-SMA and vimentin. The final 2 categories were indeterminate or nonimmunoreactive (3 specimens) and mixed (2 specimens). CONCLUSIONS: Immunohistochemistry can diagnose retrocorneal membranes of different provenances reliably in most cases. Clinical correlations established that these membranes develop after serious inflammatory disorders, prolonged wounding or ulcerations, and multiple surgeries (an average of 3.4 per patient). (Am J Ophthalmol 2010; 150:230-242. (C) 2010 by Elsevier Inc. All rights reserved.) C1 [Jakobiec, Frederick A.; Bhat, Pooja] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Bhat, Pooja] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, 243 Charles St,Suite 321, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 40 TC 22 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 2010 VL 150 IS 2 BP 230 EP 242 DI 10.1016/j.ajo.2010.03.011 PG 13 WC Ophthalmology SC Ophthalmology GA 635ZT UT WOS:000280697800015 PM 20579631 ER PT J AU Kanoff, JM Turalba, AV Andreoli, MT Andreoli, CM AF Kanoff, Justin M. Turalba, Angela V. Andreoli, Michael T. Andreoli, Christopher M. TI Characteristics and Outcomes of Work-Related Open Globe Injuries SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EYE INJURIES; RISK-FACTORS; TRAUMA; ENDOPHTHALMITIS; EPIDEMIOLOGY; WORKPLACE AB PURPOSE: To evaluate the characteristics and outcomes of patients treated for open globe injuries sustained at work and to compare these results to patients injured outside of work. DESIGN: Retrospective chart review of 812 consecutive patients with open globe injuries treated at the Massachusetts Eye and Ear Infirmary between 1999 and 2008. METHODS: A total of 146 patients with open globe injuries sustained at work were identified and their characteristics and outcomes were compared with the rest of the patients in the database. RESULTS: Of the patients injured at work, 98% were men, and the average age of the patients was 35.8 years (17-72 years). The most common mechanism of injury was penetrating trauma (56%); 38 patients examined had intraocular foreign bodies (IOFB). Nine work-related open globe injuries resulted in enucleation. There was a higher incidence of IOFBs (P = .0001) and penetrating injuries (P = .0005) in patients injured at work. Both the preoperative (P = .0001) and final best-corrected visual acuity (P = .0001) was better in the work-related group. The final visual acuity was better than 20/200 in 74.1% of cases of work-related open globe injuries. However, there was no difference observed in the rate of enucleations (P = .4). CONCLUSIONS: Work-related injuries can cause significant morbidity in a young population of patients. Based on average patient follow-up and final visual acuity, those injured at work do at least as well as, if not potentially better than, those with open globe injuries sustained outside of work. While the statistically higher rate of IOFB in the work population is not surprising, it does emphasize the importance of strict adherence to the use of eye protection in the workplace. (Am J Ophthalmol 2010;150:265-269. (C) 2010 by Elsevier Inc. All rights reserved.) C1 [Kanoff, Justin M.; Turalba, Angela V.; Andreoli, Christopher M.] Harvard Univ, Sch Med, Boston, MA USA. [Kanoff, Justin M.; Turalba, Angela V.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Andreoli, Michael T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Andreoli, Christopher M.] Harvard Vanguard Med Associates, Boston, MA USA. RP Kanoff, JM (reprint author), Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Justin_Kanoff@meei.harvard.edu NR 15 TC 26 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD AUG PY 2010 VL 150 IS 2 BP 265 EP 269 DI 10.1016/j.ajo.2010.02.015 PG 5 WC Ophthalmology SC Ophthalmology GA 635ZT UT WOS:000280697800019 PM 20522411 ER PT J AU Kong, JA Kim, GH Wei, MJ Sun, T Li, G Liu, SQ Li, XM Bhan, I Zhao, Q Thadhani, R Li, YC AF Kong, Juan Kim, Gene H. Wei, Minjie Sun, Tao Li, George Liu, Shu Q. Li, Xinmin Bhan, Ishir Zhao, Qun Thadhani, Ravi Li, Yan Chun TI Therapeutic Effects of Vitamin D Analogs on Cardiac Hypertrophy in Spontaneously Hypertensive Rats SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RENIN-ANGIOTENSIN SYSTEM; DIABETIC-NEPHROPATHY; GENE-EXPRESSION; D-RECEPTOR; 1,25-DIHYDROXYVITAMIN D-3; CARDIOVASCULAR MORTALITY; AT1 RECEPTOR; RISK; 25-HYDROXYVITAMIN-D; ALISKIREN AB Vitamin D inhibits renin expression and blocks the compensatory induction of renin associated with the use of renin-angiotensin system inhibitors. Here we test the therapeutic effects of two commonly used vitamin D analogs and their combination with losartan on the development of left ventricular hypertrophy. One-month-old male spontaneously hypertensive rats were treated with vehicle, losartan, paricalcitol, doxercalciferol, a combination of losartan and paricalcitol, or a combination of losartan and doxercalciferol for 2 months. Blood pressure was markedly reduced by losartan, but not by paricalcitol or doxercalciferol alone. Echocardiograpy demonstrated a 65 to 80% reduction in left ventricular wall thickness with losartan, paricalcitol, or doxercalciferol monotherapy and almost complete prevention of left ventricular hypertrophy with the combination therapies. Attenuation of cardiac and cardiomyocyte hypertrophy, and suppression of atrial and brain natriuretic peptides, were most marked in the combination therapy groups. These changes were well correlated with left ventricular gene and microRNA expression profiles in the different treatment groups. Renal and cardiac renin expression was markedly increased in losartan-treated animals, but nearly normalized with combination therapy. The same vitamin D analogs suppressed plasma renin activity in patients receiving chronic hemodialysis. These data demonstrate that vitamin D analogs have potent anti-hypertrophic activity in part via suppression of renin in the kidney and heart, and combination of these analogs with losartan achieves much better therapeutic effects because of the blockade of the compensatory renin increase. (Am J Pathol 2010, 177:622-631; DOI: 10.2353/ajpath.2010.091292) C1 [Kong, Juan; Wei, Minjie; Zhao, Qun; Li, Yan Chun] China Med Univ, Shengjing Hosp, Lab Metab Dis Res & Drug Dev, Shenyang, Peoples R China. [Kong, Juan; Kim, Gene H.; Sun, Tao; Li, George; Li, Yan Chun] Univ Chicago, Dept Med, Div Biol Sci, Chicago, IL 60637 USA. [Liu, Shu Q.] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Li, Xinmin] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. [Bhan, Ishir; Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA. RP Li, YC (reprint author), China Med Univ, Shengjing Hosp, Lab Metab Dis Res & Drug Dev, 900 E 57th St,KCBD,Mailbox 9, Shenyang, Peoples R China. EM thadhani.ravi@mgh.harvard.edu; cyan@medicine.bsd.uchicago.edu RI Liu, Shu/B-7626-2009; Sun, Tao/F-8233-2012 FU Genzyme Corp.; Abbott Laboratories; National Natural Science Foundation of China [30971401]; National Institutes of Health-National Heart, Lung, and Blood Institute [HL085793, HL093954] FX Supported by research grants from Genzyme Corp., Abbott Laboratories, National Natural Science Foundation of China (grant 30971401), and National Institutes of Health-National Heart, Lung, and Blood Institute (grants HL085793 and HL093954). NR 48 TC 51 Z9 60 U1 0 U2 7 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2010 VL 177 IS 2 BP 622 EP 631 DI 10.2353/ajpath.2010.091292 PG 10 WC Pathology SC Pathology GA 638KU UT WOS:000280894600014 PM 20616348 ER PT J AU Annamalai, L Bhaskar, V Pauley, DR Knight, H Williams, K Lentz, M Ratai, E Westmoreland, SV Gonzalez, RG O'Neil, SP AF Annamalai, Lakshmanan Bhaskar, Veena Pauley, Douglas R. Knight, Heather Williams, Kenneth Lentz, Margaret Ratai, Eva Westmoreland, Susan V. Gonzalez, R. Gilberto O'Neil, Shawn P. TI Impact of Short-Term Combined Antiretroviral Therapy on Brain Virus Burden in Simian Immunodeficiency Virus-Infected and CD8(+) Lymphocyte-Depleted Rhesus Macaques SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; HIV-ASSOCIATED DEMENTIA; POLYMERASE-CHAIN-REACTION; CEREBROSPINAL-FLUID; CELLULAR-LOCALIZATION; COMBINATION THERAPY; NEURONAL INJURY; VIRAL LOAD; TNF-ALPHA AB Antiretroviral drugs suppress virus burden in the cerebrospinal fluid of HIV-infected individuals; however, the direct effect of antiretrovirals on virus replication in brain parenchyma is poorly understood. We investigated the effect of short-term combined antiretroviral therapy (CART) on brain virus burden in rhesus monkeys using the CD8-depletion model of accelerated simian immunodeficiency virus (SW) encephalitis. Four monkeys received CART (consisting of the nonpenetrating agents PMPA and RCV) for four weeks, beginning 28 days after SW inoculation. Lower virus burdens were measured by real-time RT-PCR in four of four regions of brain from monkeys that received CART as compared with four SIV-infected, untreated controls; however, the difference was only significant for the frontal cortex (P < 0.05). In contrast, significantly lower virus burdens were measured in plasma and four of five lymphoid compartments from animals that received CART. Surprisingly, despite normalization of neuronal function in treated animals, the numbers of activated macrophages/microglia and the magnitude of TNF-alpha mRNA expression in brain were similar between treated animals and controls. These results suggest that short-term therapy with antiretrovirals that fail to penetrate the blood-cerebrospinal fluid barrier can reduce brain virus burden provided systemic virus burden is suppressed; however, longer treatment may be required to completely resolve encephalitic lesions and microglial activation, which may reflect the longer half-life of the principal target cells of HIV/SIV in the brain (macrophages) versus lymphoid tissues (T lymphocytes). (Am J Patbol 2010, 177:777-791; DOI: 10.2353/ajpatb.2010.091248; DOI: 10.2353/ajpatb.2010.091248) C1 [Annamalai, Lakshmanan; Pauley, Douglas R.; Knight, Heather; Westmoreland, Susan V.; O'Neil, Shawn P.] Harvard Univ, Div Comparat Pathol, New England Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. [Bhaskar, Veena; Lentz, Margaret; Ratai, Eva; Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Williams, Kenneth] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. RP Westmoreland, SV (reprint author), Harvard Univ, Div Comparat Pathol, New England Primate Res Ctr, Sch Med, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM susan_westmoreland@hms.harvard.edu RI ANNAMALAI, LAKSHMANAN/F-4220-2011 FU National Institutes of Health; National Institute of Neurological Disorders and Stroke; National Center for Research Resources [RR000150, NS048831, NS050041, NS40237] FX Supported in part by grants from the National Institutes of Health, National Institute of Neurological Disorders and Stroke, and National Center for Research Resources, including RR000150 (S.P.O.), NS048831 (to S.P.O.), NS050041 (R.G.G.), and NS40237 (K.W.). NR 96 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2010 VL 177 IS 2 BP 777 EP 791 DI 10.2353/ajpath.2010.091248 PG 15 WC Pathology SC Pathology GA 638KU UT WOS:000280894600028 PM 20595631 ER PT J AU Morgenroth, DC Orendurff, MS Shakir, A Segal, A Shofer, J Czerniecki, JM AF Morgenroth, David C. Orendurff, Michael S. Shakir, Ali Segal, Ava Shofer, Jane Czerniecki, Joseph M. TI The Relationship Between Lumbar Spine Kinematics during Gait and Low-Back Pain in Transfemoral Amputees SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Amputation; Biomechanics; Low-Back Pain; Rehabilitation ID TRANS-FEMORAL AMPUTEES; LEVEL WALKING; RESIDUAL LIMB; MOTION; OSTEOARTHRITIS; DEGENERATION; AMPUTATIONS; RELIABILITY; DISABILITY; DISC AB Objective: Low-back pain is an important cause of secondary disability in transfemoral amputees. The primary aim of our study is to assess the differences in lumbar spine kinematics during gait between transfemoral amputees with and without low-back pain. Design: Lumbar spine kinematics in three planes were measured when the subjects walked in a motion analysis laboratory. Nine transfemoral amputees with low-back pain, eight transfemoral amputees without low-back pain, and six healthy, nonamputee subjects participated. Results: The Amputee Pain and Amputee No Pain groups were essentially the same in terms of all demographic and potentially confounding variable measures. Transfemoral amputees with low-back pain showed greater transverse plane rotational excursion in their lumbar spine during walking when compared with transfemoral amputees without low-back pain (P = 0.029; effect size = 1.03). There were no significant differences in sagittal or coronal plane lumbar spine excursions during walking between these two groups. Conclusions: Although our study design does not allow for proving causation, increased transverse plane rotation has been associated with intervertebral disc degeneration, suggesting that increased transverse plane rotation secondary to walking with a prosthetic limb may be a causative factor in the etiology of low-back pain in transfemoral amputees. Identifying differences in lumbar motion can lead to potential preventative and therapeutic intervention strategies. C1 [Morgenroth, David C.; Orendurff, Michael S.; Shakir, Ali; Shofer, Jane; Czerniecki, Joseph M.] VA Puget Sound Hlth Care Syst, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Seattle, WA USA. [Morgenroth, David C.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Segal, Ava] Western Reserve Spine & Pain Inst, Kent, OH USA. RP Morgenroth, DC (reprint author), VAPSHCS, Rehabil Care Serv RCS 117, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Morgenroth, David/0000-0002-0226-7775 NR 39 TC 21 Z9 22 U1 5 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2010 VL 89 IS 8 BP 635 EP 643 DI 10.1097/PHM.0b013e3181e71d90 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 628JK UT WOS:000280115400004 PM 20647781 ER PT J AU Cifu, DX Cohen, SI Lew, HL Jaffee, M Sigford, B AF Cifu, David X. Cohen, Sara I. Lew, Henry L. Jaffee, Michael Sigford, Barbara TI The History and Evolution of Traumatic Brain Injury Rehabilitation in Military Service Members and Veterans SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Review DE Rehabilitation; War; Veterans; Brain Injury ID COGNITIVE REHABILITATION; HEAD-INJURY; FOLLOW-UP; BLAST; POLYTRAUMA; WAR; SOLDIERS; IMPAIRMENTS; INVOLVEMENT; EPILEPSY AB The field of traumatic brain injury has evolved since the time of the Civil War in response to the needs of patients with injuries and disabilities resulting from war. The Department of Veterans Affairs and the Defense and Veterans Brain Injury Center have been in the forefront of the development of the interdisciplinary approach to the rehabilitation of soldiers with traumatic brain injury, particularly those injured from the recent conflicts in Iraq and Afghanistan. The objectives of this literature review are to examine how the casualties resulting from major wars in the past led to the establishment of the current model of evaluation and treatment of traumatic brain injury and to review how the field has expanded in response to the growing cohort of military service members and veterans with TBI. C1 [Cifu, David X.] Virginia Commonwealth Univ, PM&R Serv, Hunter Holmes McGuire VA Healthcare Syst, Richmond, VA 23284 USA. [Lew, Henry L.] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Richmond, VA 23284 USA. [Cohen, Sara I.] VA Boston Healthcare Syst, Boston, MA USA. [Cohen, Sara I.] Harvard Univ, Sch Med, Boston, MA USA. [Jaffee, Michael] Def & Vet Brain Injury Ctr, Washington, DC USA. RP Lew, HL (reprint author), Virginia Commonwealth Univ, Def & Vet Brain Injury Ctr, 730 E Broad St, Richmond, VA 23284 USA. NR 45 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD AUG PY 2010 VL 89 IS 8 BP 688 EP 694 DI 10.1097/PHM.0b013e3181e722ad PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 628JK UT WOS:000280115400011 PM 20647782 ER PT J AU Yu, T Wu, X Gupta, KB Kucik, DF AF Yu, Tao Wu, Xing Gupta, Kiran B. Kucik, Dennis F. TI Affinity, lateral mobility, and clustering contribute independently to beta(2)-integrin-mediated adhesion SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE single particle tracking; intracellular cell adhesion molecule-1; E-selectin; flow chamber; rolling ID INSIDE-OUT ACTIVATION; CELL-ADHESION; EXTENDED CONFORMATIONS; LEUKOCYTE TRAFFICKING; MECHANICAL-PROPERTIES; INTEGRIN ACTIVATION; AVIDITY MODULATION; ACTIN CYTOSKELETON; STRUCTURAL BASIS; LIGAND-BINDING AB Yu T, Wu X, Gupta KB, Kucik DF. Affinity, lateral mobility, and clustering contribute independently to beta(2)-integrin-mediated adhesion. Am J Physiol Cell Physiol 299: C399-C410, 2010. First published May 5, 2010; doi: 10.1152/ajpcell.00039.2009.-Affinity changes and avidity modulation both contribute to activation of beta(2)-integrin-mediated adhesion, an essential, early step in inflammation. Avidity modulation, defined as an increase in adhesiveness independent of integrin conformational changes, might be due to integrin clustering, motion, or both. Increased integrin diffusion upon leukocyte activation has been demonstrated, but whether it is proadhesive in itself, or just constitutes a mechanism for integrin clustering, remains unclear. To understand the proadhesive effects of integrin affinity changes, clustering, and motion, an experimental system was devised to separate them. Clustering and integrin motion together were induced by cytochalasin D (CD) without inducing high-affinity; integrin motion could then be frozen by fixation; and high affinity was induced independently by Mn2+. Adhesion was equivalent for fixed and unfixed cells except following pretreatment with CD or Mn2+, which increased adhesion for both. However, fixed cells were less adhesive than unfixed cells after CD, even though integrin clustering was similar. A simple explanation is that CD induces both clustering and integrin motion, fixation then stops motion on fixed cells, but integrins continue to diffuse on unfixed cells, increasing the kinetics of integrin/ICAM-1 interactions to enhance adhesion. Affinity changes are then independent of, and additive to, avidity effects. C1 [Yu, Tao; Wu, Xing; Gupta, Kiran B.; Kucik, Dennis F.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Kucik, Dennis F.] Univ Alabama, Dept Biomed Engn, Birmingham, AL 35294 USA. [Kucik, Dennis F.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Kucik, DF (reprint author), Univ Alabama, Dept Pathol, Kaul Bldg,Rm 640A,619 S 19th St, Birmingham, AL 35294 USA. EM kucik@uab.edu RI Yu, Tao/B-5352-2012 FU Department of Veterans Affairs FX This work was supported by a Department of Veterans Affairs Merit Award. NR 46 TC 11 Z9 11 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD AUG PY 2010 VL 299 IS 2 BP C399 EP C410 DI 10.1152/ajpcell.00039.2009 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 632CK UT WOS:000280397600024 PM 20445173 ER PT J AU Lauritzen, HPMM Schertzer, JD AF Lauritzen, Hans P. M. M. Schertzer, Jonathan D. TI Measuring GLUT4 translocation in mature muscle fibers SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE glucose transporter 4; green fluorescent protein; exofacial-tag; diabetes; glucose transport; metabolism; insulin resistance; confocal microscopy; intravital microscopy ID RAT SKELETAL-MUSCLE; CELL-SURFACE GLUT4; INCREASES GLUCOSE-TRANSPORT; TRANSVERSE TUBULAR SYSTEM; GREEN-FLUORESCENT PROTEIN; LIVING MICE; T-TUBULES; GENE-TRANSFER; INSULIN STIMULATION; VESICLE DYNAMICS AB Lauritzen HP, Schertzer JD. Measuring GLUT4 translocation in mature muscle fibers. Am J Physiol Endocrinol Metab 299: E169-E179, 2010. First published May 25, 2010; doi:10.1152/ajpendo.00066.2010.-Skeletal muscle is the major tissue for postprandial glucose disposal. Facilitated glucose uptake into muscle fibers is mediated by increases in surface membrane levels of the glucose transporter GLUT4 via insulin-and/or muscle contraction-mediated GLUT4 translocation. However, the regulatory mechanisms controlling GLUT4 translocation in skeletal muscle have been difficult to characterize at the cell biology level due to muscle tissue complexity. Muscle cell culture models have improved our understanding of GLUT4 translocation and glucose transport regulation, but in vitro muscle models lack many of the characteristics of mature muscle fibers. Thus, the molecular and cellular details of GLUT4 translocation in mature skeletal muscle are deficient. The objective of this review is to highlight how advances in recent experimental approaches translate into an enhanced understanding of the regulation of GLUT4 translocation and glucose transport in mature skeletal muscle. C1 [Lauritzen, Hans P. M. M.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Lauritzen, Hans P. M. M.] Harvard Univ, Sch Med, Boston, MA USA. [Schertzer, Jonathan D.] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada. RP Lauritzen, HPMM (reprint author), Joslin Diabet Ctr, Div Res, Room 525,1 Joslin Pl, Boston, MA 02215 USA. EM Hans.Lauritzen@joslin.harvard.edu FU Weimann Foundation; Faculty of Health Sciences, University of Copenhagen; Beckett Foundation; Danish National Research Foundation; Canadian Institutes of Health Research; Canadian Diabetes Association FX This work was supported by the Weimann Foundation; the Faculty of Health Sciences, University of Copenhagen; the Beckett Foundation; and the Danish National Research Foundation. J. D. Schertzer is supported by the Canadian Institutes of Health Research and the Canadian Diabetes Association. NR 65 TC 17 Z9 18 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 2010 VL 299 IS 2 BP E169 EP E179 DI 10.1152/ajpendo.00066.2010 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 622IG UT WOS:000279654600004 PM 20501875 ER PT J AU Chen, KT Malo, MS Moss, AK Zeller, S Johnson, P Ebrahimi, F Mostafa, G Alam, SN Ramasamy, S Warren, HS Hohmann, EL Hodin, RA AF Chen, Kathryn T. Malo, Madhu S. Moss, Angela K. Zeller, Skye Johnson, Paul Ebrahimi, Farzad Mostafa, Golam Alam, Sayeda N. Ramasamy, Sundaram Warren, H. Shaw Hohmann, Elizabeth L. Hodin, Richard A. TI Identification of specific targets for the gut mucosal defense factor intestinal alkaline phosphatase SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE lipopolysaccharide; Toll-like receptors ID INFLAMMATORY-BOWEL-DISEASE; ANTIBIOTIC-INDUCED RELEASE; PARENTERAL-NUTRITION; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; ENTERAL NUTRITION; GENE-EXPRESSION; KNOCKOUT MICE; BACTERIAL-DNA; LIPOPOLYSACCHARIDE AB Chen KT, Malo MS, Moss AK, Zeller S, Johnson P, Ebrahimi F, Mostafa G, Alam SN, Ramasamy S, Warren HS, Hohmann EL, Hodin RA. Identification of specific targets for the gut mucosal defense factor intestinal alkaline phosphatase. Am J Physiol Gastro-intest Liver Physiol 299: G467-G475, 2010. First published May 20, 2010; doi: 10.1152/ajpgi.00364.2009.-Intestinal alkaline phosphatase (IAP) is a small intestinal brush border enzyme that has been shown to function as a gut mucosal defense factor, but its precise mechanism of action remains unclear. We investigated the effects of IAP on specific bacteria and bacterial components to determine its molecular targets. Purulent fluid from a cecal ligation and puncture model, specific live and heat-killed bacteria (Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes), and a variety of proinflammatory ligands (LPS, CpG DNA, Pam-3-Cys, flagellin, and TNF) were incubated with or without calf IAP (cIAP). Phosphate release was determined by using a malachite green assay. The various fluids were applied to target cells (THP-1, parent HT-29, and IAP-expressing HT-29 cells) and IL-8 secretion measured by ELISA. cIAP inhibited IL-8 induction by purulent fluid in THP-1 cells by >35% (P < 0.005). HT29-IAP cells had a reduced IL-8 response specifically to gram-negative bacteria; >90% reduction compared with parent cells (P < 0.005). cIAP had no effect on live bacteria but attenuated IL-8 induction by heat-killed bacteria by >40% (P < 0.005). cIAP exposure to LPS and CpG DNA caused phosphate release and reduced IL-8 in cell culture by >50% (P < 0.005). Flagellin exposure to cIAP also resulted in reduced IL-8 secretion by >40% (P < 0.005). In contrast, cIAP had no effect on TNF or Pam-3-Cys. The mechanism of IAP action appears to be through dephosphorylation of specific bacterial components, including LPS, CpG DNA, and flagellin, and not on live bacteria themselves. IAP likely targets these bacterially derived molecules in its role as a gut mucosal defense factor. C1 [Chen, Kathryn T.; Malo, Madhu S.; Moss, Angela K.; Ebrahimi, Farzad; Mostafa, Golam; Alam, Sayeda N.; Ramasamy, Sundaram; Hodin, Richard A.] Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Zeller, Skye; Johnson, Paul; Warren, H. Shaw; Hohmann, Elizabeth L.] Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Chen, Kathryn T.] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. RP Hodin, RA (reprint author), Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,Wang 460, Boston, MA 02114 USA. EM rhodin@partners.org OI Kuhnen, Angela/0000-0003-4944-9143 FU National Institute of Diabetes and Digestive and Kidney Diseases [R01DK050623, R01DK047186, T325T3DK007754] FX This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants R01DK050623, R01DK047186, and T325T3DK007754. NR 51 TC 34 Z9 36 U1 0 U2 7 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 AUG PY 2010 VL 299 IS 2 BP G467 EP G475 DI 10.1152/ajpgi.00364.2009 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 633EU UT WOS:000280483200020 PM 20489044 ER PT J AU Vaporidi, K Francis, RC Bloch, KD Zapol, WM AF Vaporidi, Katerina Francis, Roland C. Bloch, Kenneth D. Zapol, Warren M. TI Nitric oxide synthase 3 contributes to ventilator-induced lung injury SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE superoxide; pulmonary edema; inflammation ID TIDAL VOLUME; ENDOTHELIAL-CELLS; MECHANICAL-STRESS; REDOX REGULATION; DEFICIENT MICE; MOUSE MODEL; KAPPA-B; TETRAHYDROBIOPTERIN; INHIBITION; KINASE AB Vaporidi K, Francis RC, Bloch KD, Zapol WM. Nitric oxide synthase 3 contributes to ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 299: L150-L159, 2010. First published May 7, 2010; doi: 10.1152/ajplung.00341.2009.-Nitric oxide synthase ( NOS) depletion or inhibition reduces ventilator-induced lung injury (VILI), but the responsible mechanisms remain incompletely defined. The aim of this study was to elucidate the role of endothelial NOS, NOS3, in the pathogenesis of VILI in an in vivo mouse model. Wild-type and NOS3-deficient mice were ventilated with high-tidal volume (HVT; 40 ml/kg) for 4 h, with and without adding NO to the inhaled gas. Additional wild-type mice were pretreated with tetrahydrobiopterin and ascorbic acid, agents that can prevent NOS-generated superoxide production. Arterial blood gas tensions, histology, and lung mechanics were evaluated after 4 h of HVT ventilation. The concentration of protein, IgM, cytokines, malondialdehyde, and 8-isoprostane were measured in bronchoalveolar lavage fluid (BALF). Myeloperoxidase activity, total and oxidized glutathione levels, and NOS-derived superoxide production were measured in lung tissue homogenates. HVT ventilation induced VILI in wild-type mice, as reflected by decreased lung compliance, increased concentrations of protein and cytokines in BALF, and oxidative stress. All indices of VILI were ameliorated in NOS3-deficient mice. Augmenting pulmonary NO levels by breathing NO during mechanical ventilation did not increase lung injury in NOS3-deficient mice. HVT ventilation increased NOS-inhibitable superoxide production in lung extracts from wild-type mice but not in those from NOS3-deficient mice. Administration of tetrahydrobiopterin and ascorbic acid ameliorated VILI in wild-type mice. Our results indicate that NOS3 contributes to ventilator-induced lung injury via increased production of superoxide. C1 [Zapol, Warren M.] Harvard Univ, Dept Anesthesia & Crit Care, Anesthesia Ctr Crit Care Res, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Anesthesia Ctr Crit Care Res, Massachusetts Gen Hosp,Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM wzapol@partners.org FU National Heart, Lung, and Blood Institute [HL-42397]; Massachusetts General Hospital (MGH); IKARIA FX This work was supported, in part, by National Heart, Lung, and Blood Institute Grant HL-42397 ( to W. M. Zapol) and by a sponsored research agreement between the Massachusetts General Hospital (MGH) and IKARIA. NR 42 TC 26 Z9 28 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2010 VL 299 IS 2 BP L150 EP L159 DI 10.1152/ajplung.00341.2009 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 644OQ UT WOS:000281389000002 PM 20453164 ER PT J AU O'Tierney, PF Anderson, DF Faber, JJ Louey, S Thornburg, KL Giraud, GD AF O'Tierney, P. F. Anderson, D. F. Faber, J. J. Louey, S. Thornburg, K. L. Giraud, G. D. TI Reduced systolic pressure load decreases cell-cycle activity in the fetal sheep heart SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE blood pressure; enalaprilat; hyperplasia; cardiomyocyte ID CARDIAC MYOCYTES; VENOUS HYPERTENSION; ANGIOTENSIN-II; NEWBORN LAMBS; OVINE FETUS; RAT HEARTS; CARDIOMYOCYTES; HYPERTROPHY; MATURATION; PLASMA AB O'Tierney PF, Anderson DF, Faber JJ, Louey S, Thornburg KL, Giraud GD. Reduced systolic pressure load decreases cell-cycle activity in the fetal sheep heart. Am J Physiol Regul Integr Comp Physiol 299: R573-R578, 2010. First published May 19, 2010; doi: 10.1152/ajpregu.00754.2009.-The fetal heart is highly sensitive to changes in mechanical load. We have previously demonstrated that increased cardiac load can stimulate cell cycle activity and maturation of immature cardiomyocytes, but the effects of reduced load are not known. Sixteen fetal sheep were given either continuous intravenous infusion of lactated Ringer solution (LR) or enalaprilat, an angiotensin-converting enzyme inhibitor beginning at 127 days gestational age. After 8 days, fetal arterial pressure in the enalaprilat-infused fetuses (23.8 +/- 2.8 mmHg) was lower than that of control fetuses (47.5 +/- 4.7 mmHg) (P < 0.0001). Although the body weights of the two groups of fetuses were similar, the heart weight-to-body weight ratios of the enalaprilat-infused fetuses were less than those of the LR-infused fetuses (5.6 +/- 0.5 g/kg vs. 7.0 +/- 0.6 g/kg, P < 0.0001). Dimensions of ventricular myocytes were not different between control and enalaprilat-infused fetuses. However, there was a significant decrease in cell cycle activity in both the right ventricle (P < 0.005) and the left ventricle (P < 0.002) of the enalaprilat-infused fetuses. Thus, we conclude a sustained reduction in systolic pressure load decreases hyperplastic growth in the fetal heart. C1 [O'Tierney, P. F.; Anderson, D. F.; Faber, J. J.; Louey, S.; Thornburg, K. L.; Giraud, G. D.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. [Thornburg, K. L.; Giraud, G. D.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Anderson, D. F.; Faber, J. J.; Louey, S.; Thornburg, K. L.; Giraud, G. D.] Oregon Hlth & Sci Univ, Dept Med Cardiovasc Med, Portland, OR 97239 USA. [Giraud, G. D.] Portland VA Med Ctr, Portland, OR USA. RP Giraud, GD (reprint author), Oregon Hlth & Sci Univ, Heart Res Ctr CH15H, Div Cardiovasc Med, Portland, OR 97239 USA. EM giraudg@ohsu.edu FU American Heart Association [0720139Z]; National Institutes of Health [P01HD34430] FX Perrie O'Tierney is a recipient of an American Heart Association Postdoctoral Fellowship (0720139Z). This research was funded by a National Institutes of Health Program Project Grant (P01HD34430), the Department of Veterans Affairs, and the M. Lowell Edwards Endowment. NR 24 TC 10 Z9 10 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD AUG PY 2010 VL 299 IS 2 BP R573 EP R578 DI 10.1152/ajpregu.00754.2009 PG 6 WC Physiology SC Physiology GA 634GW UT WOS:000280569800019 PM 20484695 ER PT J AU Mount, DB AF Mount, David B. TI Regulated endocytosis of NCC SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article ID NA+-CL-COTRANSPORTER; SODIUM-CHLORIDE COTRANSPORTER; BLOOD-PRESSURE; MOLECULAR PHYSIOLOGY; SIGNALING PATHWAY; DIETARY SALT; WNK KINASES; RAT-KIDNEY; PHOSPHORYLATION; HYPERTENSION C1 [Mount, David B.] VABHS, Div Renal, Boston, MA 02130 USA. [Mount, David B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RP Mount, DB (reprint author), VABHS, Div Renal, 150 S Huntington Ave, Boston, MA 02130 USA. EM dmount@rics.bwh.harvard.edu FU NIDDK NIH HHS [DK070756] NR 35 TC 2 Z9 2 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 2010 VL 299 IS 2 BP F297 EP F299 DI 10.1152/ajprenal.00280.2010 PG 3 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 634FV UT WOS:000280566600002 PM 20504880 ER PT J AU Baggett, TP Rigotti, NA AF Baggett, Travis P. Rigotti, Nancy A. TI Cigarette Smoking and Advice to Quit in a National Sample of Homeless Adults SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID ADVERSE CHILDHOOD EXPERIENCES; NUTRITION EXAMINATION SURVEY; HEALTH INTERVIEW SURVEY; UNITED-STATES; RISK-FACTORS; FOOD INSUFFICIENCY; SUBSTANCE-ABUSE; CESSATION; WOMEN; OCCUPATION AB Background: Cigarette smoking is common among homeless people, but its characteristics in this vulnerable population have not been studied at a national level. Whether homeless smokers receive advice to quit from healthcare providers is also unknown. Purpose: To determine the prevalence and predictors of current cigarette smoking, smoking cessation, and receipt of clinician advice to quit in a national sample of homeless adults. Methods: This study analyzed data from 966 adult respondents to the 2003 Health Care for the Homeless User Survey, representing more than 436,000 people nationally. Using multivariable logistic regression, the independent predictors of smoking, quitting, and receiving advice to quit were identified. Analyses were conducted in 2008-2009. Results: The prevalence of current smoking was 73%. The lifetime quit rate among ever smokers was 9%. Among past-year smokers, 54% reported receiving clinician advice to quit. Factors independently associated with current smoking included out-of-home placement in childhood (AOR=2.79, 95% CI=1.03, 7.52); victimization while homeless (AOR=2.36, 95% CI=1.15, 4.83); past-year employment (AOR=2.52, 95% CI=1.13, 5.58); and prior illicit drug use (AOR=7.21, 95% CI=3.11, 16.7) or problem alcohol use (AOR=7.42, 95% CI=2.51, 21.9). Respondents with multiple homeless episodes had higher odds of receiving quit advice (AOR=2.51, 95% CI=1.30, 4.83) but lower odds of quitting (AOR=0.47, 95% CI=0.29, 0.78). Conclusions: Compared to the general population, homeless people are far more likely to smoke and much less likely to quit, even though more than half of smokers received quit advice in the past year. Interventions for homeless smokers should address the unique comorbidities and vulnerabilities of this population. (Am J Prey Med 2010;39(2):164-172) (C) 2010 American Journal of Preventive Medicine C1 [Baggett, Travis P.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Baggett, Travis P.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Baggett, TP (reprint author), 5 Staniford St,9th Floor, Boston, MA 02114 USA. EM tbaggett@partners.org FU NHLBI NIH HHS [K24 HL4440] NR 64 TC 63 Z9 63 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD AUG PY 2010 VL 39 IS 2 BP 164 EP 172 DI 10.1016/j.amepre.2010.03.024 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 632MP UT WOS:000280429100008 PM 20621264 ER PT J AU Baldessarini, RJ Tondo, L Ghiani, C Lepri, B AF Baldessarini, Ross J. Tondo, Leonardo Ghiani, Carmen Lepri, Beatrice TI Illness Risk Following Rapid Versus Gradual Discontinuation of Antidepressants SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID LONG-TERM TREATMENT; LITHIUM TREATMENT; BIPOLAR DISORDER; MAJOR DEPRESSION; DRUG-TREATMENT; WITHDRAWAL; ABRUPT; MAINTENANCE; PREVENTION; MANAGEMENT AB Objective: Rapid discontinuation of some psychotropic medications is followed by discontinuation symptoms as well as an increased risk of early illness recurrence. Recurrence occurs earlier after rapid than after gradual discontinuation with lithium and antipsychotics. The authors compared illness recurrence after rapid versus gradual discontinuation of antidepressants. Method: The authors compared 398 patients with a DSM-IV diagnosis of recurrent major depressive disorder (N=224), panic disorder (N=75), bipolar II disorder (N=62), or bipolar I disorder (N=37). Two-thirds were women, the mean age was 42 years, and patients were treated with antidepressants for a mean of 8.5 months. Antidepressants were discontinued clinically, either rapidly (over 1-7 days; N=188) or gradually (over 14 days or more; N=210), with a mean follow-up duration of 2.8 years; patients who were ill at discontinuation were excluded from the analysis. The authors compared latency to first new illness episodes using survival analysis and Cox multivariate modeling. Results: The latency to first illness with rapid discontinuation was 0.4 times that with gradual discontinuation, and the latency after rapid discontinuation was one-fourth the estimated average previous interepisode interval in the same patients. The effect was similar across antidepressant classes and across years; the pace of discontinuation had less effect with drugs of prolonged half-life. The effect also varied by diagnosis (bipolar I >= panic > bipolar II >= major depressive disorder) but not by episodes per year, duration of index illness, use of concomitant treatment, or antidepressant dose or duration. Conclusions: The recurrence risk for depression or panic was much shorter after rapid than after gradual discontinuation of antidepressants. These findings have implications for both clinical management and the design and interpretation of clinical trials. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychopharmacol Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Int Consortium Mood Disorders Res, McLean Div, Boston, MA 02114 USA. Univ Cagliari, Dept Psychol, Sardinia, Italy. Lucio Bini Mood Disorders Ctr, Cagliari, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 312, 115 Mill St, Belmont, MA 02478 USA. EM rjb@mclean.org FU AstraZeneca; Auritec; Biotrofix; Eli Lilly; IFI; Janssen; JDS-Noven; Luitpold; Merck; NeuroHealing; Novartis; Pfizer; SK Bio-Pharmaceuticals; Solvay Corporation; Solvay; NIH [MH-073579]; Lucio Bini Private Donors Mood Disorders Research Fund; Bruce J. Anderson Foundation; McLean Private Donors Psychopharmacology Research Fund FX Dr. Baldessarini has been a consultant to or received research support from AstraZeneca, Auritec, Biotrofix, Eli Lilly, IFI, Janssen, JDS-Noven, Luitpold, Merck, NeuroHealing, Novartis, Pfizer, SK Bio-Pharmaceuticals, and Solvay Corporation and has taught or prepared CME materials for New England Educational Institute and Pri-Med. Dr. Tondo has been a consultant to or received research support from IFI, Janssen, Eli Lilly, Merck, and Solvay. Drs. Ghiani and Lepri report no financial relationships with commercial interests.; Supported in part by NIH grant MH-073579 to Drs. Tondo and Baldessarini; the Lucio Bini Private Donors Mood Disorders Research Fund to Dr. Tondo and a grant from the Bruce J. Anderson Foundation and the McLean Private Donors Psychopharmacology Research Fund to Dr. Baldessarini. NR 36 TC 35 Z9 35 U1 1 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2010 VL 167 IS 8 BP 934 EP 941 DI 10.1176/appi.ajp.2010.09060880 PG 8 WC Psychiatry SC Psychiatry GA 634OS UT WOS:000280593400010 PM 20478876 ER PT J AU Papakostas, GI Mischoulon, D Shyu, I Alpert, JE Fava, M AF Papakostas, George I. Mischoulon, David Shyu, Irene Alpert, Jonathan E. Fava, Maurizio TI S-Adenosyl Methionine (SAMe) Augmentation of Serotonin Reuptake Inhibitors for Antidepressant Nonresponders With Major Depressive Disorder: A Double-Blind, Randomized Clinical Trial SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; OUTCOMES AB Objective: Despite the progressive increase in the number of antidepressants, many patients with major depressive disorder continue to be symptomatic. Clearly, there is an urgent need to develop better tolerated and more effective treatments for this disorder. The use of S-adenosyl methionine (SAMe), a naturally occurring molecule that serves as a methyl donor in human cellular metabolism, as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development. Method: Participants were 73 serotonin reuptake inhibitor (SRI) nonresponders with major depressive disorder enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe (target dose: 800 mg/twice daily). Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial. The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM D). Results: The HAM D response and remission rates were higher for patients treated with adjunctive SAMe (36.1% and 25.8%, respectively) than adjunctive placebo (17.6% versus 11.7%, respectively). The number needed to treat for response and remission was approximately one in six and one in seven, respectively. There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason (20.6% versus 29.5%, respectively), due to adverse events (5.1% versus 8.8%, respectively), or due to inefficacy (5.1% versus 11.7%, respectively). Conclusions: These preliminary results suggest that SAMe can be an effective, well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication. C1 [Papakostas, George I.; Mischoulon, David; Shyu, Irene; Alpert, Jonathan E.; Fava, Maurizio] Harvard Univ, Massachusetts Gen Hosp, Depress Clin & Res Program, Sch Med,Ctr Treatment Resistant Depress, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Depress Clin & Res Program, Sch Med,Ctr Treatment Resistant Depress, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU Bristol-Myers Squibb; Forest Pharmaceuticals; National Institute of Mental Health [5-K23 MH-069629]; Pamlab; Pfizer; Ridge Diagnostics; Abbott Laboratories; Alkermes; Aspect Medical Systems; AstraZeneca; Cephalon; Cyberonics; Eli Lilly; GlaxoSmithKline; J and J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals; Wyeth-Ayerst Laboratories; Bio Research; Brain-Cells; Clinical Trial Solutions; Ganeden Biotech; NARSAD; National Center for Complementary and Alternative Medicine; National Institute on Drug and Alcohol Abuse; Organon Inc.; Sanofi-Aventis; Shire; Synthelabo; Advanced Meeting Partners; American Psychiatric Association; Belvoir; Boehringer-Ingelheim; Imedex; PharmaStar; Massachusetts General Hospital Psychiatry Academy/Primedia; Massachusetts General Hospital Psychiatry Academy/Reed-Elsevier; UBC Pharma FX Dr. Papakostas has served as a consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Evotec AG, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab, Pfizer, Pierre Fabre Laboratories, Shire Pharmaceuticals, and Wyeth; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, Otsuka Pharmaceuticals, Pamlab, Pfizer, Pierre Fabre Laboratories, Shire Pharmaceuticals, Titan Pharmaceuticals, and Wyeth; he has received research support from Bristol-Myers Squibb, Forest Pharmaceuticals, the National Institute of Mental Health, Pamlab, Pfizer, and Ridge Diagnostics (formerly known as Precision Human Biolaboratories); and he has served on the speaker's bureau for Bristol-Myers Squibb and Pfizer. Dr. Mischoulon has received research support for other clinical trials in the form of donated medications from Amarin (Laxdale), Bristol-Myers Squibb, Cederroth, Lichtwer Pharma GmbH, Nordic Naturals, and Swiss Medica; he has received consulting and writing honoraria from Pamlab; he has received speaking honoraria from Bristol-Myers Squibb, Nordic Naturals, Pfizer, Pamlab, and Virbac as well as from Reed Medical Education (a company working as a logistics collaborator for the Massachusetts General Hospital Psychiatry Academy); and he has received royalty income from Back Bay Scientific for PMS Escape (patent application pending). Dr. Alpert has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, Cephalon, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, J and J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, and Wyeth-Ayerst Laboratories; he has participated on the advisory boards of or as a consultant to Eli Lilly, Pamlab, and Pharmavite; and he has received speaker's honoraria from Eli Lilly, Janssen, Organon, and Reed Medical Education. Dr. Fava has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, Bio Research, Brain-Cells, Bristol-Myers Squibb, Cephalon, Clinical Trial Solutions, Eli Lilly, Forest Pharmaceuticals, Ganeden Biotech, GlaxoSmithKline, J and J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, the National Center for Complementary and Alternative Medicine, the National Institute on Drug and Alcohol Abuse, the National Institute of Mental Health, Novartis, Organon Inc.; , Pamlab, Pfizer, Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Synthelabo, and Wyeth-Ayerst Laboratories; he has served on the advisory boards of or as a consultant to Abbott Laboratories, Amarin, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, BioMarin Pharmaceuticals, Biovail Pharmaceuticals, Brain-Cells, Bristol-Myers Squibb, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly, EPIX Pharmaceuticals, Euthymics Bioscience, Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Grunenthal GmbH Janssen Pharmaceutica, Jazz Pharmaceuticals, J and J Pharmaceuticals, Knoll Pharmaceuticals, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, Pamlab, Pfizer, PharmaStar, Pharmavite, Precision Human Biolaboratory, PsychoGenics, Roche, Sanoi-Aventis, Sepracor, Schering-Plough, Solvay Pharmaceuticals, Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, Trans-Form Pharmaceuticals, Transcept Pharmaceuticals, Vanda Pharmaceuticals, and Wyeth-Ayerst Laboratories; he has received speaker and publishing fees from Advanced Meeting Partners, the American Psychiatric Association, AstraZeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Imedex, Novartis, Organon, Pfizer, PharmaStar, Massachusetts General Hospital Psychiatry Academy/Primedia, Massachusetts General Hospital Psychiatry Academy/Reed-Elsevier, UBC Pharma, and Wyeth-Ayerst Laboratories; he is a shareholder with Compellis; he has patent applications for sequential parallel comparison of design and for a combination of azapirones and bupropion in major depressive disorder; and he receives copyright royalties for the following Massachusetts General Hospital assessment tools: the Cognitive and Physical Functioning Questionnaire, the Sexual Functioning Inventory, the Antidepressant Treatment Response Questionnaire, the Discontinuation-Emergent Sign and Symptom scale, and SAFER. Ms. Shyu reports no financial relationships with commercial interests.; Funded by a National Institute of Mental Health grant (5-K23 MH-069629). NR 16 TC 94 Z9 97 U1 4 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2010 VL 167 IS 8 BP 942 EP 948 DI 10.1176/appi.ajp.2009.09081198 PG 7 WC Psychiatry SC Psychiatry GA 634OS UT WOS:000280593400011 PM 20595412 ER PT J AU Kimerling, R Street, AE Pavao, J Smith, MW Cronkite, RC Holmes, TH Frayne, SM AF Kimerling, Rachel Street, Amy E. Pavao, Joanne Smith, Mark W. Cronkite, Ruth C. Holmes, Tyson H. Frayne, Susan M. TI Military-Related Sexual Trauma Among Veterans Health Administration Patients Returning From Afghanistan and Iraq SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MENTAL-HEALTH; ASSAULT HISTORY; FEMALE VETERANS; WOMEN; CARE; WAR; OUTPATIENTS; HARASSMENT; PREVALENCE; DISCLOSURE AB We examined military-related sexual trauma among deployed Operation Enduring Freedom and Operation Iraqi Freedom veterans. Of 125729 veterans who received Veterans Health Administration primary care or mental health services, 15.1% of the women and 0.7% of the men reported military sexual trauma when screened. Military sexual trauma was associated with increased odds of a mental disorder diagnosis, including post-traumatic stress disorder, other anxiety disorders, depression, and substance use disorders. Sexual trauma is an important postdeployment mental health issue in this population. (Am J Public Health. 2010;100:1409-1412. doi:10.2105/ AJPH.2009.171793) C1 [Kimerling, Rachel; Pavao, Joanne] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA 94025 USA. [Kimerling, Rachel; Cronkite, Ruth C.; Frayne, Susan M.] VA Palo Alto Hlth Care Syst, Ctr Hlth Care Evaluat, Menlo Pk, CA 94025 USA. [Street, Amy E.] VA Boston Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Street, Amy E.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Smith, Mark W.] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA 94025 USA. [Smith, Mark W.; Cronkite, Ruth C.] Stanford Univ, Ctr Primary Care & Outcomes Res, Sch Med, Stanford, CA 94305 USA. [Holmes, Tyson H.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Frayne, Susan M.] Stanford Univ, Sch Med, Div Gen Internal Med, Stanford, CA 94305 USA. RP Kimerling, R (reprint author), VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, 795 Willow Rd,334 PTSD, Menlo Pk, CA 94025 USA. EM rachel.kinzerling@va.gov RI Smith, Mark/G-1522-2012; OI Smith, Mark/0000-0002-4582-9088; Kimerling, Rachel/0000-0003-0996-4212 FU Health Services Research and Development Service, US Department of Veterans Affairs [IAE 05-291, SDR 07-331] FX Funding was provided by the Health Services Research and Development Service, US Department of Veterans Affairs (IAE 05-291 and SDR 07-331). NR 29 TC 129 Z9 130 U1 0 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 AUG PY 2010 VL 100 IS 8 BP 1409 EP 1412 DI 10.2105/AJPH.2009.171793 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656RR UT WOS:000282354800015 PM 20558808 ER PT J AU Lillie-Blanton, M Stone, VE Jones, AS Levi, J Golub, ET Cohen, MH Hessol, NA Wilson, TE AF Lillie-Blanton, Marsha Stone, Valerie E. Jones, Alison Snow Levi, Jeffrey Golub, Elizabeth T. Cohen, Mardge H. Hessol, Nancy A. Wilson, Tracey E. TI Association of Race, Substance Abuse, and Health Insurance Coverage With Use of Highly Active Antiretroviral Therapy Among HIV-Infected Women, 2005 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID INTERAGENCY HIV; UNITED-STATES; DRUG-USE; COHORT; CARE AB Objectives. We examined racial/ethnic disparities in highly active antiretroviral therapy (HAART) use and whether differences are moderated by substance use or insurance status, using data from the Women's Interagency HIV Study (WIHS). Methods. Logistic regression examined HAART use in a longitudinal cohort of women for whom HAART was clinically indicated in 2005 (N=1354). Results. Approximately 3 of every 10 eligible women reported not taking HAART. African American and Hispanic women were less likely than were White women to use HAART. After we adjusted for potential confounders, the higher likelihood of not using HAART persisted for African American but not for Hispanic women. Uninsured and privately insured women, regardless of race/ethnicity, were less likely than were Medicaid enrollees to use HAART. Although alcohol use was related to HAART nonuse, illicit drug use was not. Conclusions. These findings suggest that expanding and improving insurance coverage should increase access to antiretroviral therapy across racial/ethnic groups, but it is not likely to eliminate the disparity in use of HAART between African American and White women with HIV/AIDS. (Am J Public Health. 2010; 100:1493-1499. doi:10.2105/AJPH.2008.158949) C1 [Lillie-Blanton, Marsha; Levi, Jeffrey] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Hlth Policy, Washington, DC 20006 USA. [Stone, Valerie E.] Massachusetts Gen Hosp, Primary Care Residency Program, Boston, MA 02114 USA. [Stone, Valerie E.] Massachusetts Gen Hosp, Womens HIV AIDS Program, Boston, MA 02114 USA. [Jones, Alison Snow] Wake Forest Univ, Bowman Gray Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC USA. [Golub, Elizabeth T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Cohen, Mardge H.] Cook Cty Stroger Hosp, Chicago, IL USA. [Hessol, Nancy A.] Univ Calif San Francisco, Dept Clin Pharm & Med, San Francisco, CA 94143 USA. [Wilson, Tracey E.] Suny Downstate Med Ctr, Dept Community Hlth Sci, Brooklyn, NY 11203 USA. RP Lillie-Blanton, M (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Hlth Policy, 2021 K St NW,Suite 800, Washington, DC 20006 USA. EM lblanton@gwu.edu FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Institute on Drug Abuse; National Cancer Institute; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131] FX The Women's Interagency HIV Study (Wit-IS) is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and the National Institute of Child Health and Human Development (UO1-HD-32632). The WIHS is cofunded by the National Institute on Drug Abuse, the National Cancer Institute, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI grant UL1 RR024131). The National Institute on Drug Abuse provided primary funding for our study. NR 18 TC 25 Z9 25 U1 2 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 2010 VL 100 IS 8 BP 1493 EP 1499 DI 10.2105/AJPH.2008.158949 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656RR UT WOS:000282354800029 PM 19910347 ER PT J AU Nishino, M Jagannathan, JP Ramaiya, NH van den Abbeele, AD AF Nishino, Mizuki Jagannathan, Jyothi P. Ramaiya, Nikhil H. van den Abbeele, Annick D. TI Revised RECIST Guideline Version 1.1: What Oncologists Want to Know and What Radiologists Need to Know SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; oncologic imaging; response assessment; Response Evaluation Criteria in Solid Tumors; RECIST; RECIST 1.1; tumor measurement ID GASTROINTESTINAL STROMAL TUMOR; IMATINIB MESYLATE; HEPATOCELLULAR-CARCINOMA; RESPONSE EVALUATION; SOLID TUMORS; LUNG-CANCER; CRITERIA; CAVITATION; EVALUATE; THERAPY AB OBJECTIVE. The objectives of this article are to review the new Response Evaluation Criteria in Solid Tumors (RECIST) guideline, version 1.1, highlighting the major changes in the new version compared with the original RECIST guideline (version 1.0), and to present case examples with representative imaging. CONCLUSION. Familiarity with the revised RECIST is essential in day-to-day oncologic imaging practice to provide up-to-date service to oncologists and their patients. Some of the changes in the revised RECIST affect how radiologists select, measure, and report target lesions. C1 [Nishino, Mizuki; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA. EM Mizuki_Nishino@dfci.harvard.edu FU Agfa Healthcare/RSNA FX M. Nishino is supported by a 2009-2011 Agfa Healthcare/RSNA research scholar grant. NR 15 TC 94 Z9 101 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 AUG PY 2010 VL 195 IS 2 BP 281 EP 289 DI 10.2214/AJR.09.4110 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 629KT UT WOS:000280197800003 PM 20651182 ER PT J AU de Prost, N Tucci, MR Melo, MFV AF de Prost, Nicolas Tucci, Mauro R. Melo, Marcos F. Vidal TI Assessment of Lung Inflammation With (18)F-FDG PET During Acute Lung Injury SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE acute lung injury; acute respiratory distress syndrome; adults; (18)F-FDG; PET ID RESPIRATORY-DISTRESS-SYNDROME; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; DUAL-TIME-POINT; STANDARDIZED UPTAKE VALUES; HUMAN ENDOTHELIAL-CELLS; FDG-PET; METABOLIC-ACTIVITY; ATHEROSCLEROTIC PLAQUES; MECHANICAL VENTILATION AB OBJECTIVE. The purpose of this review is to describe the current experimental and clinical data regarding the fundamentals and applications of (18)F-FDG PET during acute lung injury (ALI) and acute respiratory distress syndrome ( ARDS). CONCLUSION. Lung inflammation is a key feature of ALI. During ALI, FDG PET can be used to monitor lung neutrophils, which are essential cells in the pathophysiologic mechanisms of ALI. Pulmonary FDG kinetics are altered during experimental and human ALI and are associated with regional lung dysfunction, histologic abnormalities, and prognosis. FDG PET may be a valuable noninvasive method for gaining comprehensive understanding of the mechanisms of ALI/ARDS and for evaluating therapeutic interventions. C1 [de Prost, Nicolas; Tucci, Mauro R.; Melo, Marcos F. Vidal] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org OI de Prost, Nicolas/0000-0002-4833-4320 FU NIH [HL 5R01HL086827]; LEEM Recherche; Societe de Pneumologie de Langue Francaise; CAPES (Brazilian Ministry of Education) FX Supported by NIH grant HL 5R01HL086827. N. de Prost received a scholarship from LEEM Recherche and the Societe de Pneumologie de Langue Francaise. M. R. Tucci received a scholarship from CAPES (Brazilian Ministry of Education). NR 89 TC 28 Z9 28 U1 2 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 AUG PY 2010 VL 195 IS 2 BP 292 EP 300 DI 10.2214/AJR.10.4499 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 629KT UT WOS:000280197800004 PM 20651183 ER PT J AU Ho, W Broughton, DE Donelan, K Gazelle, GS Hur, C AF Ho, Wendy Broughton, Darcy E. Donelan, Karen Gazelle, G. Scott Hur, Chin TI Analysis of Barriers to and Patients' Preferences for CT Colonography for Colorectal Cancer Screening in a Nonadherent Urban Population SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE colorectal cancer screening; CT colonography; patient preferences ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLLEGE-OF-RADIOLOGY; SOCIETY-TASK-FORCE; CONVENTIONAL COLONOSCOPY; VIRTUAL COLONOSCOPY; ADENOMATOUS POLYPS; JOINT GUIDELINE; SURVEILLANCE; ACCEPTANCE AB OBJECTIVE. The aim of this study was to evaluate patients' barriers against colorectal cancer screening tests and to assess patients' preferences and cost influences for CT colonography (CTC) in a nonadherent urban subpopulation. SUBJECTS AND METHODS. Patients who had been offered colorectal cancer screening but were nonadherent were asked to participate in this questionnaire study. Patients' demographic information was obtained, and patients' reasons for not being screened were explored. Subjects were given an information sheet that described a CTC procedure and then were asked about their willingness to undergo CTC and about other relevant factors, such as fees. RESULTS. One hundred seventy-five patients were invited to participate; 53 declined and 54 did not respond, which left 68 subjects to be included in the analysis. After being informed about CTC screening, most (83%) subjects stated that they would be willing to undergo a CTC study. However, 70% stated that they would not be willing to pay out-of-pocket fees if insurance did not cover the study, and even among the 30% who were willing to pay the fees, the average amount they were willing to pay ( mean, $244; median, $150) was well below currently charged rates. CONCLUSION. Our study suggests that most nonadherent patients would be willing to undergo CTC as long as out-of-pocket fees are reasonable. C1 [Ho, Wendy; Broughton, Darcy E.; Hur, Chin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ho, Wendy] Univ Calif Los Angeles, Ctr Digest Dis, Los Angeles, CA USA. [Donelan, Karen; Gazelle, G. Scott; Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Donelan, Karen] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Donelan, Karen; Gazelle, G. Scott; Hur, Chin] Harvard Univ, Sch Med, Boston, MA USA. [Gazelle, G. Scott] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 FU American Gastroenterological Association's; National Cancer Institute [K07CA107060] FX This work was supported in part by the American Gastroenterological Association's Research Scholar Award (grant to C. Hur) and the National Cancer Institute (grant K07CA107060 to C. Hur). NR 14 TC 13 Z9 13 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2010 VL 195 IS 2 BP 393 EP 397 DI 10.2214/AJR.09.3500 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 629KT UT WOS:000280197800016 PM 20651195 ER PT J AU Blake, MA Prakash, P Cronin, CG AF Blake, Michael A. Prakash, Priyanka Cronin, Carmel G. TI PET/CT for Adrenal Assessment SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE adrenal glands; adrenal incidentalomas; adrenal masses; PET/CT ID POSITRON-EMISSION-TOMOGRAPHY; F-18-FDG PET/CT; MASSES; TUMORS; CT; LESIONS; GLAND C1 [Blake, Michael A.; Prakash, Priyanka; Cronin, Carmel G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Blake, Michael A.; Prakash, Priyanka; Cronin, Carmel G.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Blake, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mblake2@partners.org NR 17 TC 5 Z9 5 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2010 VL 195 IS 2 BP W91 EP W95 DI 10.2214/AJR.09.3845 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 629KT UT WOS:000280197800039 PM 20651179 ER PT J AU Roh, JH Srivastava, A Lauwers, GY An, J Jang, KT Park, CK Sohn, TS Kim, S Kim, KM AF Roh, Ji Hyeon Srivastava, Amitabh Lauwers, Gregory Y. An, Jungsuk Jang, Kee-Taek Park, Cheol Keun Sohn, Tae Sung Kim, Sung Kim, Kyoung-Mee TI Micropapillary Carcinoma of Stomach A Clinicopathologic and Immunohistochemical Study of 11 Cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE gastric; micropapillary; adenocarcinoma; immunohistochemistry ID SALIVARY DUCT CARCINOMA; PROGNOSTIC-SIGNIFICANCE; GASTRIC-CANCER; SEROUS CARCINOMA; POOR-PROGNOSIS; CELL CARCINOMA; PAROTID-GLAND; ADENOCARCINOMA; EXPRESSION; MUC6 AB Micropapillary carcinoma (MPC) of the stomach is a rare, newly recognized entity, and only 2 patients with this histology have been reported. We investigated clinicopathologic features, expression of mucin (MUC2, MUC5AC, MUC6, CD10) and cytokeratin profiles (CK7 and CK20), epidermal growth factor receptors (EGFR and HER2), prognostic markers (p53 and Ki-67), and outcomes in 11 MPCs of the stomach. The proportion of MPC component ranged from 5% to 70%. Micropapillary features were often found at the deep advancing edge of the tumor. Endolymphatic tumor emboli were found in 10 cases (91%) and lymph node metastases were found in 4 cases (36%). In MPCs, positive expression was observed for Ki-67 (82%), CK7 (73%), EGFR (64%), p53 (64%), MUC5AC (45%), MUC6 (36%), and CK20 (27%). However, MUC2, CD10, and HER2 expression was negative in all cases. In 9 conventional adenocarcinomas and 11 papillary adenocarcinomas with multiple endolymphatic tumor emboli, used as control, positive expression was observed for Ki-67 (100%), CK7 (90%), EGFR (80%), CK20 (70%), p53 (70%), MUC5AC (70%), MUC6 (60%), MUC2 (40%), CD10 (25%), and HER2 (15%). Expression of MUC2, CK20, and the Ki-67 labeling index was significantly higher in control adenocarcinomas as compared with MPCs (P < 0.05). However, there was no significant difference in other clinicopathologic features and overall patient survival. Subclassification of MPCs into 2 subgroups according to the proportion of micropapillary component (cut-off value was 20%) failed to find any significant clinicopathologic differences (P > 0.05). Although MPCs in other organs show a poor prognosis, this does not seem to be true for gastric MPCs. Further larger studies are necessary to confirm our initial findings. C1 [Roh, Ji Hyeon; An, Jungsuk; Jang, Kee-Taek; Park, Cheol Keun; Kim, Kyoung-Mee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul 135710, South Korea. [Sohn, Tae Sung; Kim, Sung] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Surg, Seoul 135710, South Korea. [Srivastava, Amitabh] Dartmouth Hitchcock Med Ctr Lebanon, Dartmouth Med Sch, Dept Pathol, Lebanon, NH USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kim, KM (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, 50 Ilwon Dong, Seoul 135710, South Korea. EM kkmkys@skku.edu RI Kim, Sung/G-4114-2014 NR 36 TC 19 Z9 24 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 AUG PY 2010 VL 34 IS 8 BP 1139 EP 1146 DI 10.1097/PAS.0b013e3181e7043b PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 631TV UT WOS:000280372900007 PM 20661012 ER PT J AU Sholl, LM Barletta, JA Yeap, BY Chirieac, LR Hornick, JL AF Sholl, Lynette M. Barletta, Justine A. Yeap, Beow Y. Chirieac, Lucian R. Hornick, Jason L. TI Sox2 Protein Expression is an Independent Poor Prognostic Indicator in Stage I Lung Adenocarcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Sox2; prognosis; lung; adenocarcinoma; immunohistochemistry; biomarkers ID NONSMALL CELL; STEM-CELLS; CANCER; SURVIVAL; CARCINOMAS; SIGNATURE; GENOME AB Many patients with stage I nonsmall cell lung carcinoma will develop recurrence after surgical excision. Sox2 is a marker of embryonic stem cell pluripotency that is associated with aggressive tumor behavior and is expressed in a subset of lung adenocarcinomas. We hypothesized that Sox2 expression may provide prognostic information in early stage lung adenocarcinomas. We evaluated formalin-fixed, paraffinembedded tissue from 104 stage I lung adenocarcinomas resected between 1997 and 2000. Sox2 expression was analyzed by immunohistochemistry and compared with clinicopathologic features, time-to-progression, and overall survival (OS). Sox2 expression was detected in 50% of the cases and was more frequent in tumors from older and male patients but not significantly associated with smoking status, tumor stage, grade, or histologic subtype. Compared with Sox2-negative tumors, Sox2 expression predicted a shorter time-to-progression (49% vs. 82% at 5 y; P = 0.0006) and shorter OS (54% vs. 79% at 5 y; P = 0.004). By multivariate analysis, Sox2 expression predicted a greater risk of progression among men [hazard ratio (HR) 5.6; 95% confidence interval (CI) 2.3-13.8] and women (HR 2.1; 95% CI 0.8-5.7). Sox2 expression was associated with significantly shorter OS among men (HR 2.5; 95% CI 1.2-5.1), but not in women. Sox2 seems to be an independent predictor of poor outcome in stage I lung adenocarcinomas and may help stratify patients at increased risk for recurrence. C1 [Sholl, Lynette M.; Barletta, Justine A.; Chirieac, Lucian R.; Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Yeap, Beow Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Hornick, JL (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jhornick@partners.org FU Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) [2P50 CA090578-06] FX Supported in part by Dana-Farber/Harvard Cancer Center Specialized Programs of Research Excellence (SPORE) in Lung Cancer 2P50 CA090578-06 (LRC). The authors have no financial disclosures. NR 30 TC 69 Z9 84 U1 1 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 AUG PY 2010 VL 34 IS 8 BP 1193 EP 1198 DI 10.1097/PAS.0b013e3181e5e024 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 631TV UT WOS:000280372900015 PM 20631605 ER PT J AU Afrin, LB AF Afrin, Lawrence B. TI Fatal Copper Deficiency From Excessive Use of Zinc-Based Denture Adhesive SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Zinc toxicity; Copper deficiency; Sensorimotor neuropathy; Myelodysplasia; Denture adhesive ID NEUROLOGIC DISEASE; HYPOCUPREMIA; NEUROPATHY AB Introduction: Human stores of zinc and copper exist in dynamic equilibrium; an increase in one causes a fall in the other, and clinical consequences of toxicity or deficiency of one or the other may result. Some of the most widely used denture adhesives are zinc based, creating a potential for zinc toxicity and corresponding copper deficiency. A case of denture adhesive-based zinc toxicity with corresponding copper deficiency leading to fatal ascending sensorimotor polyneuropathy was identified. The objectives of this study were to illustrate the evolution, and disparate response to treatment, of neurologic and hematologic abnormalities resulting from copper deficiency, and to discuss opportunities to mitigate denture adhesive-related zinc toxicity. Methods: Detailed clinical and laboratory data for the subject patient were compiled. The patient received copper supplementation. Copper and zinc levels were obtained posttreatment at varying intervals. Results: Hematologic and neurologic abnormalities progressed, as excessive use of zinc-based denture adhesive persisted. Hematologic and neurologic consultants were initially considered purely hematologic or neurologic diagnoses. Eventual consideration of unifying hypotheses led to definitive diagnosis 10 months after presentation. Hematologic abnormalities responded to copper supplementation, but neurologic abnormalities did not. The patient died of aspiration likely due to severe sensorimotor polyneuropathy. Conclusions: Early recognition of copper deficiency and improved warnings regarding excessive use of zinc-based denture adhesives may be the routes to improved outcomes. C1 [Afrin, Lawrence B.] Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. [Afrin, Lawrence B.] Ralph H Johnson Vet Affairs Med Ctr, Hematol Oncol Sect, Med Serv, Charleston, SC USA. RP Afrin, LB (reprint author), Med Univ S Carolina, Div Hematol Oncol, CSB903,MSC635,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM afrinl@musc.edu NR 26 TC 13 Z9 13 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 AUG PY 2010 VL 340 IS 2 BP 164 EP 168 DI 10.1097/MAJ.0b013e3181e3648c PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 635TC UT WOS:000280678200016 PM 20555248 ER PT J AU Leach, JR Rayz, VL Soares, B Wintermark, M Mofrad, MRK Saloner, D AF Leach, Joseph R. Rayz, Vitaliy L. Soares, Bruno Wintermark, Max Mofrad, Mohammad R. K. Saloner, David TI Carotid Atheroma Rupture Observed In Vivo and FSI-Predicted Stress Distribution Based on Pre-rupture Imaging SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Patient-specific; Vulnerable plaque; Atherosclerosis; Image-based ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; ATHEROSCLEROTIC PLAQUE RUPTURE; FLUID-STRUCTURE INTERACTIONS; AMERICAN-HEART-ASSOCIATION; HISTOPATHOLOGICAL CORRELATION; ASYMPTOMATIC INDIVIDUALS; CIRCUMFERENTIAL STRESS; STRUCTURAL-ANALYSIS; SHEAR-STRESS; FIBROUS CAP AB Atherosclerosis at the carotid bifurcation is a major risk factor for stroke. As mechanical forces may impact lesion stability, finite element studies have been conducted on models of diseased vessels to elucidate the effects of lesion characteristics on the stresses within plaque materials. It is hoped that patient-specific biomechanical analyses may serve clinically to assess the rupture potential for any particular lesion, allowing better stratification of patients into the most appropriate treatments. Due to a sparsity of in vivo plaque rupture data, the relationship between various mechanical descriptors such as stresses or strains and rupture vulnerability is incompletely known, and the patient-specific utility of biomechanical analyses is unclear. In this article, we present a comparison between carotid atheroma rupture observed in vivo and the plaque stress distribution from fluid-structure interaction analysis based on pre-rupture medical imaging. The effects of image resolution are explored and the calculated stress fields are shown to vary by as much as 50% with sub-pixel geometric uncertainty. Within these bounds, we find a region of pronounced elevation in stress within the fibrous plaque layer of the lesion with a location and extent corresponding to that of the observed site of plaque rupture. C1 [Leach, Joseph R.] San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA 94121 USA. [Leach, Joseph R.; Mofrad, Mohammad R. K.; Saloner, David] UC Berkeley UC San Francisco Joint Grad Grp Bioen, Berkeley, CA USA. [Leach, Joseph R.; Rayz, Vitaliy L.; Soares, Bruno; Wintermark, Max; Saloner, David] Univ Calif San Francisco, Med Ctr, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Leach, JR (reprint author), San Francisco VA Med Ctr, Dept Radiol, Box 114D,4150 Clement St, San Francisco, CA 94121 USA. EM joseph.leach@ucsf.edu OI Wintermark, Max/0000-0002-6726-3951; Soares, Bruno/0000-0003-4185-6940 FU American Heart Association [0715072Y]; NIH [1K25NS059891]; VA; NINDS [NS059944] FX The authors would like to thank Tarik Tihan for review of the image-based plaque geometry. Funding support was provided by the following grants: American Heart Association Pre-doctoral Fellowship 0715072Y (JL), NIH Grant 1K25NS059891 (VR), VA MERIT Review Award (DS), and NS059944 from the NINDS. NR 54 TC 21 Z9 24 U1 3 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD AUG PY 2010 VL 38 IS 8 BP 2748 EP 2765 DI 10.1007/s10439-010-0004-8 PG 18 WC Engineering, Biomedical SC Engineering GA 622RD UT WOS:000279682000023 PM 20232151 ER PT J AU Farabaugh, A Sonawalla, S Johnson, DP Witte, J Papakostas, GI Goodness, T Clain, A Baer, L Mischoulon, D Fava, M Harley, R AF Farabaugh, Amy Sonawalla, Shamsah Johnson, Daniel P. Witte, Janet Papakostas, George I. Goodness, Tracie Clain, Alisabet Baer, Lee Mischoulon, David Fava, Maurizio Harley, Rebecca TI Early improvements in anxiety, depression, and anger/hostility symptoms and response to antidepressant treatment SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE major depressive disorder; anxiety; hostility; depression; Symptom Questionnaire ID DISORDER; FLUOXETINE; PREDICTORS AB BACKGROUND: The purpose of this study was to examine whether treatment response to fluoxetine by depressed outpatients was predicted by early improvement on any of 3 subscales (Anxiety, Depression, and Anger/Hostility) of the Symptom Questionnaire (SQ). METHODS: We evaluated 169 depressed outpatients (52.6% female) between ages 18 and 65 (mean age, 40.3 +/- 10.6 years) meeting DSM-III-R criteria for major depressive disorder (MDD). All patients completed the SQ at baseline (week 0) and at weeks 2, 4, and 8 of treatment with fluoxetine 20 mg/d. We defined treatment response as a >= 50% reduction in score on the 17-item Hamilton Rating Scale for Depression, and early improvement on 3 SQ subscales (Anxiety, Depression, and Anger/Hostility) as a >= 30% reduction in score by week 2. RESULTS: The percentage of patients with significant early improvement in anger was significantly greater than the percentage of those with early improvements in anxiety or depression. When early improvement on the Anxiety, Depression, and Anger/Hostility subscales of the SQ were assessed independently by logistic regression, all 3 subscales were predictors of response to treatment. CONCLUSIONS: Early improvement in anger, anxiety, and depressive symptoms may predict response to antidepressant treatment among outpatients with MDD. C1 [Farabaugh, Amy; Johnson, Daniel P.; Witte, Janet; Papakostas, George I.; Goodness, Tracie; Clain, Alisabet; Baer, Lee; Mischoulon, David; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. [Sonawalla, Shamsah] Jaslok Hosp & Res Ctr, Mumbai, Maharashtra, India. [Sonawalla, Shamsah] Duke Univ, Dept Psychiat & Behav Sci, Med Ctr, Durham, NC USA. RP Farabaugh, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM afarabaugh@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU National Institute of Mental Health [5R10MH056057-05]; Forest Pharmaceuticals; Bristol-Myers Squibb; Pamlab L.L.C.; Pfizer Inc; Ridge Diagnostic FX This research was supported in part by a grant to M. Fava from the National Institute of Mental Health (5R10MH056057-05).; Dr. Farabaugh has received research support from Forest Pharmaceuticals.; Dr. Papakostas has served as a consultant for AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab L.L.C., Pfizer Inc, Pierre Fabre Laboratories, Shire Pharmaceuticals, and Wyeth Pharmaceuticals. He has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Evotec AG, GlaxoSmithKline, lnflabloc Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, Pamlab L.L.C., Pfizer Inc, Pierre Fabre Laboratories, Shire Pharmaceuticals, Titan Pharmaceuticals, and Wyeth Pharmaceuticals. He has received research support from Bristol-Myers Squibb, Forest Pharmaceuticals, the National Institute of Mental Health, Pamlab L.L.C., Pfizer Inc, and Ridge Diagnostic (formerly known as Precision Human Biolaboratories). He has served on the speakers bureau of Bristol-Myers Squibb and Pfizer Inc. Dr. Fava has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, Clinical Trial Solutions L.L.C., Eli Lilly and Company, Forest Pharmaceuticals, Ganeden, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc., Pamlab L.L.C., Pfizer Inc, Pharmavite, Roche, Sanofi/Synthelabo, Shire Pharmaceuticals, Solvay Pharmaceuticals, and Wyeth Pharmaceuticals. He has served as a consultant/advisor for Abbott Laboratories, Affectis Pharmaceuticals, Amarinn, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc., BioMarin Pharmaceuticals, Biovail Pharmaceuticals, Inc., BrainCells, Inc., Bristol-Myers Squibb, Cephalon, Clinical Trials Solutions L.L.C, CNS Response, Cornpenis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eisai, Eli Lilly and Company, EPIX Pharmaceuticals, Euthymics Bioscience, Inc., Fabre-Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals, GlaxoSmithKline, Grunenthal GmBH, Janssen L.P., Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Inc., Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, Pamlab, L.L.C., Pfizer Inc, PharmaStar, Pharmavite, Precision Human Biolaboratory, PsychoGenics, Psylin Neurosciences, Inc., Ridge Diagnostics, Inc., Roche, Sanofi/Synthelabo, Sepracor Inc., Schering-Plough, Solvay Pharmaceuticals, Somaxon, Somerset Pharmaceuticals, Takeda, Tetragenex, TransForm Pharmaceuticals, Inc., Transcept Pharmaceuticals, Vanda Pharmaceuticals, Inc., and Wyeth Pharmaceuticals. He has served on the speakers bureau of AstraZeneca, Boehringer Ingelheim, BristolMyers Squibb, Cephalon, Eli Lilly and Company, Forest Pharmaceuticals, GlaxoSmithKline, Novartis, Organon, Pfizer Inc, PharmaStar, and Wyeth Pharmaceuticals. He has equity holdings with Compellis. Dr. Mischoulon has received research support from Ganeden, Laxdale (Amarin), and Nordic Naturals. He has served as a consultant/advisor for Bristol-Myers Squibb. He is a speaker for and has received writing support from Pamlab, L.L.C. He receives royalty/patent income from PMS Escape (patent co-holder). Dr. Sonawalla, Mr. Johnson, Ms. Goodness, Ms. Clain, Dr. Baer, and Dr. Harley report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products. NR 12 TC 10 Z9 10 U1 0 U2 2 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD AUG PY 2010 VL 22 IS 3 BP 166 EP 171 PG 6 WC Psychiatry SC Psychiatry GA 640DM UT WOS:000281028300005 PM 20680189 ER PT J AU Nyer, M Kasckow, J Fellows, I Lawrence, EC Golshan, S Solorzano, E Zisook, S AF Nyer, Maren Kasckow, John Fellows, Ian Lawrence, Edith C. Golshan, Shah Solorzano, Ellen Zisook, Sidney TI The relationship of marital status and clinical characteristics in middle-aged and older patients with schizophrenia and depressive symptoms SO ANNALS OF CLINICAL PSYCHIATRY LA English DT Article DE marriage; quality of life; suicide; subsyndromal depression; marital status; divorce ID QUALITY-OF-LIFE; INTIMATE-RELATIONSHIPS; GENDER-DIFFERENCES; UNITED-STATES; RATING-SCALE; SUICIDE; MARRIAGE; BEHAVIOR; MEN; DISORDERS AB BACKGROUND: This study examines the relationship of marital status to depression, positive and negative symptoms, quality of life, and suicidal ideation among 211 patients with schizophrenia-spectrum disorders and subsyndromal depressive symptoms. We hypothesized that single participants would have more severe symptomatology than married and cohabitating participants. METHODS: Outpatients, age 40 or older, were diagnosed with schizophrenia or schizoaffective disorders using the MINI Structured Clinical Interview for DSM-IV Axis 1 Disorders. Participants exhibited a score of >= 8 on the Hamilton Rating Scale for Depression but did not meet criteria for a major depressive episode. RESULTS: Participants who were married or cohabitating had a later age of onset of first psychotic episode or hospitalization than those who were single (age, 29.35 vs 24.21). Married participants rated their quality of life higher than those who were single (mean Quality of Life Scale scores, 72.28 vs 53.87) and had less suicidal ideation than those who were divorced, widowed, or separated (7.4% vs 29.2%). CONCLUSIONS: In middle-aged and older individuals with schizophrenia or schizoaffective disorder and depressive symptoms, marriage appeared. to enhance quality of life and protect against suicidal ideation. Efforts that focus on providing additional support for those who are experiencing divorce or separation could prove to be lifesaving for these individuals. C1 [Nyer, Maren; Lawrence, Edith C.] Univ Virginia, Dept Human Serv, Curry Sch Educ, Charlottesville, VA 22903 USA. [Kasckow, John] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. [Fellows, Ian; Golshan, Shah; Solorzano, Ellen; Zisook, Sidney] Univ Calif San Diego, Dept Psychiat, Div Geriatr Psychiat 116A 1, San Diego, CA 92103 USA. [Zisook, Sidney] VA San Diego Healthcare Syst, San Diego, CA USA. RP Nyer, M (reprint author), Univ Virginia, Dept Human Serv, Curry Sch Educ, 405 Emmet St, Charlottesville, VA 22903 USA. EM mbn4k@virginia.edu FU [MH 063931]; [MH6398] FX Supported by MH 063931(SZ) MH6398 (JWK), the VISN 4 and VISN 22 MIRECC, and the University of California, San Diego Center for Community-based Research in Older People with Psychoses. In addition J.W.K. was supported by a VISN 4 CPPF grant. We also wish to thank the Cincinnati VA Medical Center and the University of Cincinnati College of Medicine for all of their support. NR 49 TC 10 Z9 13 U1 1 U2 5 PU DOWDEN HEALTH MEDIA PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 1040-1237 J9 ANN CLIN PSYCHIATRY JI Ann. Clin. Psychiatry PD AUG PY 2010 VL 22 IS 3 BP 172 EP 179 PG 8 WC Psychiatry SC Psychiatry GA 640DM UT WOS:000281028300006 PM 20680190 ER PT J AU Ginde, AA Sullivan, AF Camargo, CA AF Ginde, Adit A. Sullivan, Ashley F. Camargo, Carlos A., Jr. TI Attrition From Emergency Medicine Clinical Practice in the United States SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID OCCUPATIONAL STRESS; PHYSICIANS; SATISFACTION; BURNOUT AB Study objective: We estimate the annual attrition from emergency medicine clinical practice. Methods: We performed a cross-sectional analysis of the American Medical Association's 2008 Physician Masterfile, which includes data on all physicians who have ever obtained a medical license in at least 1 US state. We restricted the analysis to physicians who completed emergency medicine residency training or who obtained emergency medicine board certification. We defined attrition as not being active in emergency medicine clinical practice. Attrition was reported as cumulative and annualized rates, with stratification by years since training graduation. Death rates were estimated from life tables for the US population. Results: Of the 30,864 emergency medicine trained or emergency medicine board-certified physicians, 26,826 (87%) remain active in emergency medicine clinical practice. Overall, type of attrition was 45% to non emergency medicine clinical practice, 22% retired, 14% administration, and 10% research/teaching. Immediate attrition (<2 years since training graduation) was 6.5% The cumulative attrition rates from 2 to 15 years postgraduation were stable (5% to 9%) and thereafter were progressively higher, with 18% having left emergency medicine clinical practice at 20 years postgraduation and 25% at 30 years postgraduation. Annualized attrition rates were highest for the first 5 years postgraduation and after 40 years postgraduation; between 5 and 40 years, the rates remained low (<1%). The overall annual attrition rate from emergency medicine clinical practice, including estimated death rate, was approximately 1.7%. Conclusion: Despite the high stress and demands of emergency medicine, overall attrition remains low and compares favorably with that of other medical specialties. These data have positive implications for the emergency physician workforce and are important for accurate estimation of and planning for emergency physician workforce needs. [Ann Emerg Med. 2010;56:166-171.] C1 [Ginde, Adit A.] Univ Colorado Denver, Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. [Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Ginde, AA (reprint author), Univ Colorado Denver, Sch Med, Dept Emergency Med, 12401 E 17th Ave,B-215, Aurora, CO 80045 USA. EM adit.ginde@ucdenver.edu RI Siry, Bonnie/D-7189-2017 NR 27 TC 8 Z9 8 U1 1 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 AUG PY 2010 VL 56 IS 2 BP 166 EP 171 DI 10.1016/j.annemergmed.2009.11.002 PG 6 WC Emergency Medicine SC Emergency Medicine GA 635ZM UT WOS:000280697000014 PM 20036032 ER PT J AU Wen, LS AF Wen, Leana S. TI All Quiet on Cambridge Street SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Wen, LS (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, 75 Francis St,Nevilee House 236-A, Boston, MA 02115 USA. EM LWen@partners.org OI Wen, Leana/0000-0003-0259-0537 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 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 2010 VL 56 IS 2 BP 187 EP 187 DI 10.1016/j.annemergmed.2009.12.026 PG 1 WC Emergency Medicine SC Emergency Medicine GA 635ZM UT WOS:000280697000019 PM 20643269 ER PT J AU Debette, S Beiser, A Hoffmann, U DeCarli, C O'Donnell, CJ Massaro, JM Au, R Himali, JJ Wolf, PA Fox, CS Seshadri, S AF Debette, Stephanie Beiser, Alexa Hoffmann, Udo DeCarli, Charles O'Donnell, Christopher J. Massaro, Joseph M. Au, Rhoda Himali, Jayandra J. Wolf, Philip A. Fox, Caroline S. Seshadri, Sudha TI Visceral Fat Is Associated with Lower Brain Volume in Healthy Middle-Aged Adults SO ANNALS OF NEUROLOGY LA English DT Article ID BODY-MASS INDEX; ADIPOSE-TISSUE VOLUMES; WHITE-MATTER LESIONS; STROKE RISK PROFILE; FOLLOW-UP; ALZHEIMERS-DISEASE; CENTRAL OBESITY; COGNITIVE FUNCTION; GENE-EXPRESSION; DEMENTIA AB Objective: Mid life obesity has been associated with an increased risk of dementia. The underlying mechanisms are poorly understood. Our aim was to examine the cross-sectional association of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and computed tomography (CT)-based measurements of subcutaneous (SAT) and visceral (VAT) adipose tissue with various magnetic resonance imaging (MRI) markers of brain aging in middle-aged community adults. Methods: Participants from the Framingham Offspring cohort were eligible if in addition to having measurements of BMI, WC, WHR, SAT, and VAT, they had undergone a volumetric brain MRI scan with measurements of total brain volume (TCBV), temporal horn volume (THV), white matter hyperintensity volume (WMHV), and MRI-defined brain infarcts (BI). All analyses were adjusted for age, sex, and time interval between abdominal CT and brain MRI. Results: In a sample of 733 community participants (mean age, 60 years; 53% women), we observed an inverse association of BMI (estimate by standard deviation unit +/- standard error = -0.27 +/- 0.12; p = 0.02), WC (-0.30 +/- 0.12; p = 0.01), WHR (-0.37 +/- 0.12; p = 0.02), SAT (-0.23 +/- 0.11; p = 0.04), and VAT (-0.36 +/- 0.12; p = 0.002) with TCBV, independent of vascular risk factors. The association between VAT and TCBV was the strongest and most robust, and was also independent of BMI (-0.35 +/- 0.15; p = 0.02) and insulin resistance (-0.32 +/- 0.13; p = 0.01). When adjusting for C-reactive protein levels, the associations were attenuated (-0.17 +/- 0.13; p = 0.17 for VAT). No consistently significant association was observed between the anthropometric or CT-based abdominal fat measurements and THV, WMHV, or BI. Interpretation: In middle-aged community participants, we observed a significant inverse association of anthropometric and CT-based measurements of abdominal, especially visceral, fat with total brain volume. ANN NEUROL 2010;68:136-144 C1 [Debette, Stephanie; Beiser, Alexa; Au, Rhoda; Himali, Jayandra J.; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study, Boston, MA 02118 USA. [Debette, Stephanie; Beiser, Alexa; O'Donnell, Christopher J.; Massaro, Joseph M.; Au, Rhoda; Himali, Jayandra J.; Wolf, Philip A.; Fox, Caroline S.; Seshadri, Sudha] NHLBI, Framingham Heart Study, Framingham, MA USA. [Beiser, Alexa; Massaro, Joseph M.; Himali, Jayandra J.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Hoffmann, Udo; Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. [Hoffmann, Udo; O'Donnell, Christopher J.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [DeCarli, Charles] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study, B602,72 E Concord St, Boston, MA 02118 USA. EM suseshad@bu.edu RI DeCarli, Charles/B-5541-2009; OI /0000-0003-1391-9481 FU Framingham Heart Study's National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institute of Neurological Disorders and Stroke [R01 NS17950]; National Institute on Aging [R01 AG16495, AG08122, AG033193, AG031287, AG033040, P30AG013846]; Bettencourt-Schueller Foundation FX This work was supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute contract (N01-HC-25195) and by grants from the National Institute of Neurological Disorders and Stroke (R01 NS17950 to PAW.) and from the National Institute on Aging (R01 AG16495 to P.A.W., AG08122 to P.A.W., AG033193 to S.S., AG031287 to S.S., AG033040 to P.A.W., P30AG013846 to S.S.).; Dr Debette received an award from the Bettencourt-Schueller Foundation. NR 58 TC 80 Z9 81 U1 1 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 2010 VL 68 IS 2 BP 136 EP 144 DI 10.1002/ana.22062 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 636HD UT WOS:000280721500007 PM 20695006 ER PT J AU Gandy, S Simon, AJ Steele, JW Lublin, AL Lah, JJ Walker, LC Levey, AI Krafft, GA Levy, E Checler, F Glabe, C Bilker, WB Abel, T Schmeidler, J Ehrlich, ME AF Gandy, Sam Simon, Adam J. Steele, John W. Lublin, Alex L. Lah, James J. Walker, Lary C. Levey, Allan I. Krafft, Grant A. Levy, Efrat Checler, Frederic Glabe, Charles Bilker, Warren B. Abel, Ted Schmeidler, James Ehrlich, Michelle E. TI Days to Criterion as an Indicator of Toxicity Associated with Human Alzheimer Amyloid-beta Oligomers SO ANNALS OF NEUROLOGY LA English DT Article ID HEREDITARY CEREBRAL-HEMORRHAGE; IMPAIR SYNAPTIC PLASTICITY; MOUSE MODEL; A-BETA; NATURAL OLIGOMERS; TRANSGENIC MICE; DISEASE; MEMORY; DEFICITS; PEPTIDE AB Objective: Recent evidence suggests that high molecular weight soluble oligomeric A beta (oA beta) assemblies (also known as A beta-derived diffusible ligands, or ADDLs) may represent a primary neurotoxic basis for cognitive failure in Alzheimer disease (AD). To date, most in vivo studies of oA beta/ADDLs have involved injection of assemblies purified from the cerebrospinal fluid of human subjects with AD or from the conditioned media of A beta-secreting cells into experimental animals. We sought to study the bioactivities of endogenously formed oA beta/ADDLs generated in situ from the physiological processing of human amyloid precursor protein (APP) and presenitin1 (PS1) transgenes. Methods: We produced and histologically characterized single transgenic mice overexpressing APPE(693Q) or APP(E693Q) X PS1 Delta E9 bigenic mice. APP(E693Q) mice were studied in the Morris water maze (MWM) task at 6 and 12 months of age. Following the second MWM evaluation, mice were sacrificed, and brains were assayed for A beta total, A beta 40, A beta 42, and oA beta/ADDLs by enzyme-linked immunosorbent assay (ELISA) and were also histologically examined. Based on results from the oA beta/ADDL ELISA, we assigned individual APP(E693Q) mice to either an undetectable oA beta/ADDLs group or a readily detectable oA beta/ADDLs group. A days to criterion (DTC) analysis was used to determine delays in acquisition of the MWM task. Results: Both single transgenic and bigenic mice developed intraneuronal accumulation of APP/A beta, although only APP(E693Q) X PS1 Delta 9 bigenic mice developed amyloid plaques. The APP(E693Q) mice did not develop amyloid plaques at any age studied, up to 30 months. APP(E693Q) mice were tested for spatial learning and memory, and only 12-month-old APP(E693Q) mice with readily detectable oA beta/ADDLs displayed a significant delay in acquisition of the MWM task when compared to nontransgenic littermates. Interpretation: These data suggest that cerebral oA beta/ADDL assemblies generated in brain in situ from human APP transgenes may be associated with cognitive impairment. We propose that a DTC analysis may be a sensitive method for assessing the cognitive impact in mice of endogenously generated oligomeric human A beta assemblies. ANN NEUROL 2010;68:220-330 C1 [Gandy, Sam; Steele, John W.; Lublin, Alex L.; Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Gandy, Sam; Steele, John W.; Lublin, Alex L.; Schmeidler, James] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Gandy, Sam; Steele, John W.; Lublin, Alex L.; Ehrlich, Michelle E.] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY 10029 USA. [Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY USA. [Simon, Adam J.] AJ Simon Enterprises LLC, Yardley, PA USA. [Lah, James J.; Walker, Lary C.; Levey, Allan I.] Emory Univ, Dept Neurol, Ctr Neurodegenerat Dis, Atlanta, GA 30322 USA. [Walker, Lary C.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Krafft, Grant A.] Acumen Pharmaceut Inc, Livermore, CA USA. [Levy, Efrat] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Levy, Efrat] NYU, Sch Med, Dept Pharmacol, New York, NY USA. [Levy, Efrat] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Checler, Frederic] Fdn Rech Med, Inst Mol & Cellular Pharmacol, Valbonne, France. [Glabe, Charles] Univ Calif Irvine, Sch Med, Dept Neurol, Irvine, CA 92717 USA. [Bilker, Warren B.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Abel, Ted] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. RP Gandy, S (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM samuel.gandy@mssm.edu RI Walker, L/J-6541-2015; Checler, Frederic/C-1241-2009 OI Walker, L/0000-0001-9166-3261; Checler, Frederic/0000-0003-2098-1750 FU Cure Alzheimer's Fund; VA MERIT [1I01BX000348-01]; National Institute on Aging [P01AG10491, P50AG017623, P50AG025688, P50AG05138, P01AG02219]; National Center for Research Resources [RR-00165]; National Institute of General Medical Sciences [T32GM062754]; Fondation pour la Recherche Medicale; Conseil General des Alpes Maritimes FX S.G., A.L.L., J.W.S. and M.E.E. were supported by the Cure Alzheimer's Fund, VA MERIT review grant 1I01BX000348-01, and National Institute on Aging grant P01AG10491. T.A. was supported by National Institute on Aging grant P50AG017623. J.J.L. and A.I.L. were supported by National Institute on Aging grant P50AG025688. L.C.W. was supported by National Center for Research Resources grant RR-00165. J.S. was supported by National Institute on Aging grants P50AG05138 and P01AG02219. J.W.S. is a trainee in the Integrated Pharmacological Sciences Training Program supported by grant T32GM062754 from the National Institute of General Medical Sciences. F.C. was supported by the Fondation pour la Recherche Medicale and by the Conseil General des Alpes Maritimes. NR 36 TC 54 Z9 54 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 2010 VL 68 IS 2 BP 220 EP 230 DI 10.1002/ana.22052 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 636HD UT WOS:000280721500016 PM 20641005 ER PT J AU Colwell, AS Gadd, M Smith, BL Austen, WG AF Colwell, Amy S. Gadd, Michele Smith, Barbara L. Austen, William G., Jr. TI An Inferolateral Approach to Nipple-Sparing Mastectomy Optimizing Mastectomy and Reconstruction SO ANNALS OF PLASTIC SURGERY LA English DT Article DE breast cancer reconstruction; implants; nipple-sparing; AlloDerm AB An increasing number of women presenting with early stage breast cancer or a strong family history are choosing mastectomy as a therapeutic or prophylactic treatment option. In these selected patients, conservation of the nipple areolar complex is considered to improve cosmesis and body image. Incision placement is an important consideration in breast appearance after surgery. Functionally, the incision must allow adequate access for mastectomy and implant positioning. In addition, preservation of blood supply is critical to maintain a viable nipple. This article describes an inferolateral curvilinear incision on the breast mound, which can be designed de novo or as an extension of a preexisting lateral scar. The incision allows adequate access and hides the scar on anterior view, thus optimizing both the mastectomy and reconstruction. In patients with a preexisting lateral scar, this may be the incision of choice. C1 [Colwell, Amy S.; Austen, William G., Jr.] Mass Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. [Gadd, Michele; Smith, Barbara L.] Mass Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Colwell, AS (reprint author), Mass Gen Hosp, Div Plast Surg, 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM acolwell@partners.org NR 5 TC 13 Z9 14 U1 0 U2 0 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 AUG PY 2010 VL 65 IS 2 BP 140 EP 143 DI 10.1097/SAP.0b013e3181c1fe77 PG 4 WC Surgery SC Surgery GA 630AT UT WOS:000280244200007 PM 20606592 ER PT J AU Hsu, WM Carraro, A Kulig, KM Miller, ML Kaazempur-Mofrad, M Weinberg, E Entabi, F Albadawi, H Watkins, MT Borenstein, JT Vacanti, JP Neville, C AF Hsu, Wen-Ming Carraro, Amedeo Kulig, Katherine M. Miller, Mark L. Kaazempur-Mofrad, Mohammad Weinberg, Eli Entabi, Fateh Albadawi, Hassan Watkins, Michael T. Borenstein, Jeffrey T. Vacanti, Joseph P. Neville, Craig TI Liver-Assist Device With a Microfluidics-Based Vascular Bed in an Animal Model SO ANNALS OF SURGERY LA English DT Article ID BIOARTIFICIAL LIVER; IN-VITRO; HEPATOCYTES; CHANNELS; FAILURE; ALBUMIN; FUTURE AB Objective: This study evaluates a novel liver-assist device platform with a microfluidics-modeled vascular network in a femoral arteriovenous shunt in rats. Summary of Background Data: Liver-assist devices in clinical trials that use pumps to force separated plasma through packed beds of parenchymal cells exhibited significant necrosis with a negative impact on function. Methods: Microelectromechanical systems technology was used to design and fabricate a liver-assist device with a vascular network that supports a hepatic parenchymal compartment through a nanoporous membrane. Sixteen devices with rat primary hepatocytes and 12 with human HepG2/C3A cells were tested in athymic rats in a femoral arteriovenous shunt model. Several parenchymal tube configurations were evaluated for pressure profile and cell survival. The blood flow pattern and perfusion status of the devices was examined by laser Doppler scanning. Cell viability and serum protein secretion functions were assessed. Results: Femoral arteriovenous shunt was successfully established in all animals. Blood flow was homogeneous through the vascular bed and replicated native flow patterns. Survival of seeded liver cells was highly dependent on parenchymal chamber pressures. The tube configuration that generated the lowest pressure supported excellent cell survival and function. Conclusions: This device is the first to incorporate a microfluidics network in the systemic circulatory system. The microvascular network supported viability and function of liver cells in a short-term ex vivo model. Parenchymal chamber pressure generated in an arteriovenous shunt model is a critical parameter that affects viability and must be considered in future designs. The microfluidics-based vascular network is a promising platform for generating a large-scale medical device capable of augmenting liver function in a clinical setting. C1 [Hsu, Wen-Ming; Kulig, Katherine M.; Vacanti, Joseph P.; Neville, Craig] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Entabi, Fateh; Albadawi, Hassan; Watkins, Michael T.] Massachusetts Gen Hosp, Dept Surg, Div Vasc & Endovascu Surg, Boston, MA 02114 USA. [Hsu, Wen-Ming] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Dept Surg, Taipei 10764, Taiwan. [Carraro, Amedeo] Ist Oncol Veneto, Dept Surg Oncol, Padua, Italy. [Miller, Mark L.; Watkins, Michael T.; Vacanti, Joseph P.; Neville, Craig] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Kaazempur-Mofrad, Mohammad; Weinberg, Eli] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. [Borenstein, Jeffrey T.] Charles Stark Draper Lab Inc, Ctr Biomed Engn, Cambridge, MA 02139 USA. RP Neville, C (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St,CPZN-4809, Boston, MA 02114 USA. EM neville@helix.mgh.harvard.edu OI HSU, WEN-MING/0000-0002-5145-9538 FU Center for Integration of Medicine and Innovative Technology (US Army) [DAMD17-02-2-0006] FX Supported by the Center for Integration of Medicine and Innovative Technology (US Army DAMD17-02-2-0006). NR 23 TC 17 Z9 18 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD AUG PY 2010 VL 252 IS 2 BP 351 EP 357 DI 10.1097/SLA.0b013e3181e982ba PG 7 WC Surgery SC Surgery GA 634OQ UT WOS:000280593000022 PM 20647924 ER PT J AU Tanabe, KK Jara, S Michaelson, J AF Tanabe, Kenneth K. Jara, Sebastian Michaelson, James TI Creating and Providing Predictions of Melanoma Outcome SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID LYMPH-NODES CONTRIBUTES; CANCER DEATH; PRIMARY SITE; RISK C1 [Tanabe, Kenneth K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ktanabe@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2010 VL 17 IS 8 BP 1981 EP 1982 DI 10.1245/s10434-010-1054-8 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 622HY UT WOS:000279653600003 PM 20373038 ER PT J AU Tomkiewicz, D Casadei, G Larkins-Ford, J Moy, TI Garner, J Bremner, JB Ausubel, FM Lewis, K Kelso, MJ AF Tomkiewicz, Danuta Casadei, Gabriele Larkins-Ford, Jonah Moy, Terence I. Garner, James Bremner, John B. Ausubel, Frederick M. Lewis, Kim Kelso, Michael J. TI Berberine-INF55 (5-Nitro-2-Phenylindole) Hybrid Antimicrobials: Effects of Varying the Relative Orientation of the Berberine and INF55 Components SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MULTIDRUG EFFLUX TRANSPORTER; STAPHYLOCOCCUS-AUREUS; ANTIBACTERIAL AGENTS; PUMP INHIBITOR; FLUOROQUINOLONE RESISTANCE; NORA; MECHANISMS; ELEGANS; PROTEIN; CLONING AB Hybrid antimicrobials containing an antibacterial linked to a multidrug resistance (MDR) pump inhibitor make up a promising new class of agents for countering efflux-mediated bacterial drug resistance. This study explores the effects of varying the relative orientation of the antibacterial and efflux pump inhibitor components in three isomeric hybrids (SS14, SS14-M, and SS14-P) which link the antibacterial alkaloid and known substrate for the NorA MDR pump berberine to different positions on INF55 (5-nitro-2-phenylindole), an inhibitor of NorA. The MICs for all three hybrids against wild-type, NorA-knockout, and NorA-overexpressing Staphylococcus aureus cells were found to be similar (9.4 to 40.2 mu M), indicating that these compounds are not effectively effluxed by NorA. The three hybrids were also found to have similar curing effects in a Caenorhabditis elegans live infection model. Each hybrid was shown to accumulate in S. aureus cells to a greater extent than either berberine or berberine in the presence of INF55, and the uptake kinetics of SS14 were found to differ from those of SS14-M and SS14-P. The effects on the uptake and efflux of the NorA substrate ethidium bromide into S. aureus cells in the presence or absence of the hybrids were used to confirm MDR inhibition by the hybrids. MDR-inhibitory activity was confirmed for SS14-M and SS14-P but not for SS14. Molecular dynamics simulations revealed that SS14 prefers to adopt a conformation that is not prevalent in either SS14-M or SS14-P, which may explain why some properties of SS14 diverge from those of its two isomers. In summary, subtle repositioning of the pump-blocking INF55 moiety in berberine-INF55 hybrids was found to have a minimal effect on their antibacterial activities but to significantly alter their effects on MDR pumps. C1 [Garner, James; Bremner, John B.; Kelso, Michael J.] Univ Wollongong, Sch Chem, Wollongong, NSW 2522, Australia. [Tomkiewicz, Danuta; Casadei, Gabriele; Lewis, Kim] Northeastern Univ, Dept Biol, Boston, MA 02115 USA. [Tomkiewicz, Danuta; Casadei, Gabriele; Lewis, Kim] Northeastern Univ, Antimicrobial Discovery Ctr, Boston, MA 02115 USA. [Larkins-Ford, Jonah; Moy, Terence I.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Larkins-Ford, Jonah; Moy, Terence I.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Kelso, MJ (reprint author), Univ Wollongong, Sch Chem, Northfields Ave, Wollongong, NSW 2522, Australia. EM mkelso@uow.edu.au OI Kelso, Michael/0000-0001-7809-6637 FU University of Wollongong, NSW, Australia; Harvard Medical School; Northeastern University, Boston, MA; NHMRC [252922]; American Cancer Society [PF-02-130-01-MBC]; NIH [R21 AI059483, R01 AI072508, R01 AI076372]; Broad Institute of Harvard and MIT FX We thank the University of Wollongong, NSW, Australia; Harvard Medical School; and Northeastern University, Boston, MA, for supporting this work. The award of an NHMRC C. J. Martin fellowship (fellowship 252922 to Michael J. Kelso) and an American Cancer Society postdoctoral fellowship (fellowship PF-02-130-01-MBC to Terence I. Moy) are gratefully acknowledged. The work was supported by grants R21 AI059483, R01 AI072508, and R01 AI076372 from the NIH and a grant from the Broad Institute of Harvard and MIT, awarded to Frederick M. Ausubel. NR 36 TC 16 Z9 17 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2010 VL 54 IS 8 BP 3219 EP 3224 DI 10.1128/AAC.01715-09 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 626JW UT WOS:000279963300019 PM 20498327 ER PT J AU Chaiswing, L Oberley, TD AF Chaiswing, Luksana Oberley, Terry D. TI Extracellular/Microenvironmental Redox State SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID EXTRACELLULAR-SUPEROXIDE-DISMUTASE; GAMMA-GLUTAMYL-TRANSPEPTIDASE; X(C)(-) CYSTINE/GLUTAMATE ANTIPORTER; PLASMA GLUTATHIONE-PEROXIDASE; PROTEIN DISULFIDE-ISOMERASE; NITRIC-OXIDE SYNTHASE; RENAL-CELL CARCINOMA; HYDROGEN-PEROXIDE; PROSTATE-CANCER; GROWTH-FACTOR AB Extracellular redox (reduction-oxidation) state is a factor that serves as an important regulator of cell-microenvironmental interactions and is determined by several known variables; including redox-modulating proteins that are located on the plasma membrane or outside of cells, extracellular thiol/disulfide couples, and reactive oxygen species (ROS)/reactive nitrogen species (RNS) that are capable of traveling across plasma membranes into the extracellular space. The extracellular redox state works in concert with the intracellular redox state to control both the influx and efflux of ROS/RNS that may serve to modulate redox signaling or to perturb normal cellular processes or both. Under physiologic conditions, the extracellular space is known to have a relatively more-oxidized redox state than the interior of the cell. During pathologic conditions, such as cancer, the extracellular redox state may be altered, causing specific proteins such as proteases, soluble factors, or the extracellular matrix to have altered functions or activities. Recent studies have strongly supported an important relation between the extracellular redox state and cancer cell aggressiveness. The purpose of this review is to identify redox buffer networks in extracellular spaces and to emphasize the possible roles of the extracellular redox state in cancer, knowledge that may contribute to potential therapeutic interventions. Antioxid. Redox Signal. 13, 449-465. C1 [Oberley, Terry D.] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. [Chaiswing, Luksana; Oberley, Terry D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53706 USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Room A-35,2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@wisc.edu FU Office of Research and Development, Biomedical Laboratory Research and Development Service; Department of Veterans Affairs (TDO) FX This material is based on work supported by the Office of Research and Development, Biomedical Laboratory Research and Development Service, and Department of Veterans Affairs (TDO). NR 123 TC 51 Z9 51 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD AUG PY 2010 VL 13 IS 4 BP 449 EP 465 DI 10.1089/ars.2009.3020 PG 17 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 619KI UT WOS:000279428700006 PM 20017602 ER PT J AU Salloum, S Kluge, SF Kim, AY Roggendorf, M Timm, J AF Salloum, Shadi Kluge, Silvia F. Kim, Arthur Y. Roggendorf, Michael Timm, Joerg TI The resistance mutation R155K in the NS3/4A protease of hepatitis C virus also leads the virus to escape from HLA-A*68-restricted CD8 T cells SO ANTIVIRAL RESEARCH LA English DT Article DE CD8 T cell; Immune escape; Drug resistance; STAT-C; Protease inhibitor; BILN 2061 ID TREATMENT-NAIVE; CONFERRING RESISTANCE; DRUG-RESISTANCE; RNA REPLICATION; INHIBITOR; HCV; SENSITIVITY; TELAPREVIR; POLYMERASE; INFECTION AB The NS3/4A serine protease of the hepatitis C virus (HCV) is one of the most attractive targets for specific antiviral agents. However, mutations conferring resistance may decrease the efficacy of these drugs. Although the level of resistance associated with specific mutations differs between different compounds, substitutions R155K and A156T reduce susceptibility to all protease inhibitors published so far. Interestingly, variants harboring the resistant mutation R155K were also detected as the predominant quasispecies in some treatment-naive patients. Of note, key positions for resistance overlap with the HLA-A*68-restricted epitope HAVGIFRAAV(1175-1184). The aim of our study was to analyze the impact of protease inhibitor resistance mutations on the replication level and the antiviral CD8 T cell response against this HCV epitope. Our findings suggest that the R155K variant is associated with a relatively high replication level and with a substantial loss of cross-recognition by specific CD8 T cells targeting the epitope HAVGIFRAAV(1175-1184), providing a possible explanation for its existence in the absence of drug selection pressure. (C) 2010 Elsevier B.V. All rights reserved. C1 [Salloum, Shadi; Kluge, Silvia F.; Roggendorf, Michael; Timm, Joerg] Univ Duisburg Essen, Inst Virol, D-45147 Essen, Germany. [Kim, Arthur Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. RP Timm, J (reprint author), Univ Duisburg Essen, Inst Virol, Virchowstr 179, D-45147 Essen, Germany. EM joerg.timm@uni-due.de NR 21 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD AUG PY 2010 VL 87 IS 2 SI SI BP 272 EP 275 DI 10.1016/j.antiviral.2010.05.006 PG 4 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 639KC UT WOS:000280972700020 PM 20488208 ER PT J AU Alora-Palli, MB Brouda, I Green, B Kimball, AB AF Alora-Palli, Maria B. Brouda, Irina Green, Barbara Kimball, Alexandra B. TI A Cost-effectiveness Comparison of Liquor Carbonis Distillate Solution and Calcipotriol Cream in the Treatment of Moderate Chronic Plaque Psoriasis SO ARCHIVES OF DERMATOLOGY LA English DT Letter ID COAL-TAR; EFFICACY C1 [Alora-Palli, Maria B.] Massachusetts Gen Hosp, Clin Unit Res Trials Skin, Boston, MA 02114 USA. [Brouda, Irina; Green, Barbara] NeoStrata Co Inc, Princeton, NJ USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Clin Unit Res Trials Skin, 50 Staniford St,Ste 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 9 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD AUG PY 2010 VL 146 IS 8 BP 919 EP 922 DI 10.1001/archdermatol.2010.167 PG 4 WC Dermatology SC Dermatology GA 642VS UT WOS:000281249700023 PM 20713833 ER PT J AU Herskovits, AZ Growdon, JH AF Herskovits, A. Zara Growdon, John H. TI Sharpen That Needle SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID ALZHEIMERS-DISEASE; COGNITIVE DECLINE; BIOMARKERS C1 [Growdon, John H.] Massachusetts Gen Hosp, Dept Neurol, Wang Ambulatory Care Ctr 729, Boston, MA 02114 USA. [Herskovits, A. Zara] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Growdon, JH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang Ambulatory Care Ctr 729, Boston, MA 02114 USA. EM jgrowdon@partners.org NR 12 TC 12 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2010 VL 67 IS 8 BP 918 EP 920 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 637HU UT WOS:000280809000001 PM 20697041 ER PT J AU Goldstein, JN Marrero, M Masrur, S Pervez, M Barrocas, AM Abdullah, A Oleinik, A Rosand, J Smith, EE Dzik, WH Schwamm, LH AF Goldstein, Joshua N. Marrero, Marisela Masrur, Shihab Pervez, Muhammad Barrocas, Alex M. Abdullah, Abdul Oleinik, Alexandra Rosand, Jonathan Smith, Eric E. Dzik, Walter H. Schwamm, Lee H. TI Management of Thrombolysis-Associated Symptomatic Intracerebral Hemorrhage SO ARCHIVES OF NEUROLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE ISCHEMIC-STROKE; QUALITY-OF-CARE; INTRACRANIAL HEMORRHAGE; GUIDELINES-STROKE; THERAPY; TRANSFORMATION; INTRAARTERIAL; WARFARIN; OUTCOMES AB Background: Symptomatic intracerebral hemorrhage (sICH) is the most devastating complication of thrombolytic therapy for acute stroke. It is not clear whether patients with sICH continue to bleed after diagnosis, nor has the most appropriate treatment been determined. Methods: We performed a retrospective analysis of our prospectively collected Get With the Guidelines Stroke database between April 1, 2003, and December 31, 2007. Radiologic images and all procoagulant agents used were reviewed. Multivariable logistic regression was performed to identify factors associated with in-hospital mortality. Results: Of 2362 patients with acute ischemic stroke during the study period, sICH occurred in 19 of the 311 patients (6.1%) who received intravenous tissue plasminogen activator and 2 of the 72 (2.8%) who received intra-arterial thrombolysis. In-hospital mortality was significantly higher in patients with sICH than in those without (15 of 20 [75.0]% vs 56 of 332 [16.9%], P < .001). Eleven of 20 patients (55.0%) received therapy for co-agulopathy: 7 received fresh frozen plasma; 5, cryoprecipitate; 4, phytonadione (vitamin K(1)); 3, platelets; and 1, aminocaproic acid. Independent predictors of in-hospital mortality included sICH (odds ratio, 32.6; 95% confidence interval, 8.8-120.2), increasing National Institutes of Health Stroke Scale score (1.2; 1.1-1.2), older age (1.3; 1.0-1.7), and intra-arterial thrombolysis (2.9; 1.4-6.0). Treatment for coagulopathy was not associated with outcome. Continued bleeding (>33% increase in intracerebral hemorrhage volume) occurred in 4 of 10 patients with follow-up scans available (40.0%). Conclusions: In many patients with sICH after thrombolysis, coagulopathy goes untreated. Our finding of continued bleeding after diagnosis in 40.0% of patients suggests a powerful opportunity for intervention. A multicenter registry to analyze management of thrombolysis-associated intracerebral hemorrhage and outcomes is warranted. C1 [Goldstein, Joshua N.; Marrero, Marisela] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Masrur, Shihab; Pervez, Muhammad; Abdullah, Abdul; Oleinik, Alexandra; Rosand, Jonathan; Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dzik, Walter H.] Massachusetts Gen Hosp, Dept Hematol, Boston, MA 02114 USA. [Barrocas, Alex M.] Mt Sinai Med Ctr, Dept Radiol, Miami Beach, FL 33140 USA. [Smith, Eric E.] Univ Calgary, Calgary Stroke Program, Calgary, AB, Canada. RP Goldstein, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 0 Emerson Pl,Ste 3B, Boston, MA 02114 USA. EM jgoldstein@partners.org RI Goldstein, Joshua/H-8953-2016; OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU NINDS [NS059774] FX This study was funded in part by K23 career development award NS059774 from the NINDS (Dr Goldstein). NR 31 TC 35 Z9 38 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2010 VL 67 IS 8 BP 965 EP 969 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 637HU UT WOS:000280809000008 PM 20697046 ER PT J AU Buracchio, T Dodge, HH Howieson, D Wasserman, D Kaye, J AF Buracchio, Teresa Dodge, Hiroko H. Howieson, Diane Wasserman, Dara Kaye, Jeffrey TI The Trajectory of Gait Speed Preceding Mild Cognitive Impairment SO ARCHIVES OF NEUROLOGY LA English DT Article ID OLDER PERSONS; PARKINSONIAN SIGNS; ALZHEIMER-DISEASE; COMMUNITY POPULATION; DECLINE; PEOPLE; RISK; DYSFUNCTION; DEMENTIA; PROGRESSION AB Objectives: To compare the trajectory of motor decline, as measured by gait speed and finger-tapping speed, between elderly people who developed mild cognitive impairment (MCI) and those who remained cognitively intact. We also sought to determine the approximate time at which the decline in motor function accelerated in persons who developed MCI. Design: Longitudinal cohort study. Participants: Participants were 204 healthy seniors (57.8% women) from the Oregon Brain Aging Study evaluated for up to 20 years using annual neurologic, neuropsychological, and motor examinations. Main Outcome Measures: The pattern of motor decline with aging was compared using a mixed-effects model with an interaction term for age and a clinical diagnosis of MCI. The time before diagnosis of MCI, when the change in gait or finger-tapping speed accelerates, was assessed using a mixed-effects model with a change point for men and women, separately and combined, who developed MCI. Results: The rates of change, with aging, in gait speed (P < .001) and finger-tapping speed in the dominant hand (P=.003) and nondominant hand (P < .001) were significantly different between participants who developed MCI (converters) and those who did not (nonconverters). Using a change point analysis for MCI converters, the decrease in gait speed accelerated by 0.023 m/s/y (P < .001), occurring 12.1 years before the onset of MCI. An acceleration in gait speed decline occurred earlier in men than women. For tapping speed, the change point occurred after the onset of MCI for both dominant and nondominant hands when men and women were combined. Conclusions: Motor decline as indexed by gait speed accelerates up to 12 years before MCI. Longitudinal changes in motor function may be useful in the early detection of dementia during preclinical stages, when the utility of disease-modifying therapies would be greatest. C1 [Buracchio, Teresa; Kaye, Jeffrey] Portland VA Med Ctr, Portland, OR USA. [Kaye, Jeffrey] Oregon Ctr Aging & Technol, Portland, OR USA. [Buracchio, Teresa; Dodge, Hiroko H.; Howieson, Diane; Wasserman, Dara; Kaye, Jeffrey] Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, Portland, OR 97239 USA. RP Buracchio, T (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Dis Ctr, 3181 SW Sam Jackson Pk Rd,Mail Code CR-131, Portland, OR 97239 USA. EM buracchi@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU Department of Veterans Affairs [P30AG008017, R01AG024059]; National Institute on Aging [K01AG023014]; National Center for Research Resources FX This study was supported by the Department of Veterans Affairs; grants P30AG008017, R01AG024059, and K01AG023014 from the National Institute on Aging; and the National Center for Research Resources. NR 40 TC 107 Z9 108 U1 2 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2010 VL 67 IS 8 BP 980 EP 986 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 637HU UT WOS:000280809000011 PM 20697049 ER PT J AU Hayden, KM Breitner, JCS Welsh-Bohmer, KA AF Hayden, Kathleen M. Breitner, John C. S. Welsh-Bohmer, Kathleen A. TI Apolipoprotein E epsilon 4 Status and Cognitive Decline With and Without Dementia Reply SO ARCHIVES OF NEUROLOGY LA English DT Letter ID DISEASE; APOE C1 [Hayden, Kathleen M.] Duke Univ, Dept Psychiat & Behav Sci, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Durham, NC 27705 USA. [Hayden, Kathleen M.; Welsh-Bohmer, Kathleen A.] Duke Univ, Div Neurol, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, Dept Med,Med Ctr, Durham, NC 27705 USA. [Breitner, John C. S.] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Breitner, John C. S.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Hayden, KM (reprint author), Duke Univ, Dept Psychiat & Behav Sci, Joseph & Kathleen Bryan Alzheimers Dis Res Ctr, 2200 W Main St,Ste A-200, Durham, NC 27705 USA. EM khayden@duke.edu RI Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 NR 4 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2010 VL 67 IS 8 BP 1036 EP 1037 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 637HU UT WOS:000280809000028 ER PT J AU Ku, TK Rutar, T Han, Y Porco, TC Naseri, A AF Ku, Tina K. Rutar, Tina Han, Ying Porco, Travis C. Naseri, Ayman TI Resident-Performed Phacoemulsification Surgery in Tamsulosin-Treated Patients SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID FLOPPY-IRIS-SYNDROME; BENIGN PROSTATIC HYPERTROPHY; CATARACT-SURGERY; CLINICAL FINDINGS; VITREOUS LOSS; IFIS; COMPLICATIONS; ASSOCIATION; PROPHYLAXIS; EPINEPHRINE AB Objectives: To compare intraoperative complication rates and visual outcomes for patients treated and not treated with tamsulosin hydrochloride who underwent resident-performed phacoemulsification, and to determine whether the recognition of intraoperative floppy iris syndrome in 2005 affected the subsequent complication rates for tamsulosin-treated patients. Methods: This comparative retrospective cohort study included 101 tamsulosin-treated eyes and 404 non tamsulosin-treated eyes from January 1, 1998, to August 31, 2008. Main outcome measures were major and minor complication rates and postoperative best-corrected visual acuity. Complication rates were compared between August 11, 1999, to December 31, 2005, and January 1, 2006, to September 3, 2008, for both tamsulosin-treated and non tamsulosin-treated eyes. Results: The major complication rates were 3.0% for tamsulosin-treated eyes and 8.9% for non-tamsulosin-treated eyes (P=.08), while the minor complication rates were 24.8% and 12.1%, respectively (P=.002). Both groups had an equal likelihood of attaining better than 20/40 postoperative visual acuities (82.2% vs 82.9%, rdspectively; P=.85). Frequency of major complications between tamsulosin-treated and non tamsulosin-treated eyes was 6.0% vs 15.8%, respectively (P=.09), from August 11, 1999, to December 31, 2005, compared with 0.0% vs 2.0%, respectively (P>.99), from January 1, 2006, to September 3, 2008. Conclusions: Differences in the major complication rates for tamsulosin-treated and non tamsulosin-treated eyes were not significant, whereas tamsulosin exposure was associated with a significant increase in minor complications. Both groups had similar, good postoperative visual outcomes. After 2005, a reduction in major complications was seen in both groups, attributed to programmatic changes in surgical education. Recognition of intraoperative floppy iris syndrome did not impart a significant additional protective effect in preventing major complications. C1 [Naseri, Ayman] San Francisco VA Med Ctr, Dept Ophthalmol, San Francisco, CA 94121 USA. [Ku, Tina K.; Rutar, Tina; Han, Ying; Porco, Travis C.; Naseri, Ayman] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Porco, Travis C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Prevent Med & Publ Hlth, San Francisco, CA 94143 USA. [Porco, Travis C.; Naseri, Ayman] Francis I Proctor Fdn Res Ophthalmol, San Francisco, CA USA. RP Naseri, A (reprint author), San Francisco VA Med Ctr, Dept Ophthalmol, 4150 Clement St, San Francisco, CA 94121 USA. EM ayman.naseri@va.gov FU Research to Prevent Blindness; University of California [NIH P30]; That Man May See FX This work was supported in part by unrestricted grants from Research to Prevent Blindness, the University of California Institutional Core Grant For Vision Research (NIH P30), and That Man May See, a non-profit organization. NR 37 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2010 VL 128 IS 8 BP 967 EP 972 PG 6 WC Ophthalmology SC Ophthalmology GA 638QJ UT WOS:000280909700002 PM 20696995 ER PT J AU Lane, AM Egan, KM Kim, IK Gragoudas, ES AF Lane, Anne Marie Egan, Kathleen M. Kim, Ivana K. Gragoudas, Evangelos S. TI Mortality After Diagnosis of Small Melanocytic Lesions of the Choroid SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID NATIONAL DEATH INDEX; MALIGNANT MELANOMAS; UVEAL MELANOMA; CILIARY BODY; HOST FACTORS; NEVI; RISK; GROWTH; HISTOGENESIS; ENUCLEATION AB Objective: To evaluate the risk of dying of metastatic choroidal melanoma in patients with small, indeterminate, pigmented lesions of the uveal tract. Methods: A cohort of 1063 consecutive patients were evaluated in the Ocular Oncology Clinic of the Massachusetts Eye and Ear Infirmary between January 1976 and June 1996 with definite choroidal nevus (n = 256), indeterminate lesions (n = 334), or small melanoma (n = 373). Deaths occurring up to December 1998 were identified through active follow-up or by a search of the National Death Index. Cumulative death rates were compared among diagnostic groups using the Kaplan-Meier method. Results: Mean lesion diameter was 4.6 mm in the nevi, 7.0 mm in the indeterminate lesions, and 8.1 mm in the small melanomas. Patients ranged in age from 3 to 95 years (median, 64 years). A total of 15 deaths due to ocular melanoma were ascertained (median follow-up of survivors, 8.2 years), 13 in the melanoma group and 2 in the indeterminate lesion group; actuarial tumor-specific death rates at 10 years after evaluation were 5% (95% confidence interval, 3%-8%) and 1% (95% confidence interval 0%-3%), respectively. No deaths due to ocular melanoma occurred in the nevus group. Conclusions: These data document the very low malignant potential of most indeterminate melanocytic lesions of the choroid and support the current practice of monitoring these tumors, with treatment provided when growth and other signs of malignant transformation are observed. C1 [Lane, Anne Marie] Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. [Egan, Kathleen M.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 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 Research to Prevent Blindness FX This study was supported by Research to Prevent Blindness (Dr Kim). NR 31 TC 5 Z9 5 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2010 VL 128 IS 8 BP 996 EP 1000 PG 5 WC Ophthalmology SC Ophthalmology GA 638QJ UT WOS:000280909700006 PM 20696999 ER PT J AU Brigger, MT Cunningham, MJ Hartnick, CJ AF Brigger, Matthew T. Cunningham, Michael J. Hartnick, Christopher J. TI Dexamethasone Administration and Postoperative Bleeding Risk in Children Undergoing Tonsillectomy SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID PEDIATRIC TONSILLECTOMY; ADENOTONSILLECTOMY; HEMORRHAGE; MANAGEMENT; PAIN; METAANALYSIS; MORBIDITY; SAFETY; NAUSEA AB Objective: To assess whether administration of dexamethasone during tonsillectomy is associated with a dose-dependent increased rate of postoperative tonsillectomy hemorrhage. Design: Retrospective review of 2788 children and adolescents who underwent tonsillectomy with or without adenoidectomy for sleep-disordered breathing or infectious tonsillitis and received perioperative dexamethasone between January 1, 2002, and March 3, 2009. Patients underwent 1 of 3 methods of tonsillectomy, including extracapsular electrosurgical tonsillectomy, extracapsular radiofrequency ablation tonsillectomy, or intracapsular microdebrider tonsillotomy. Setting: Massachusetts Eye and Ear Infirmary. Patients: Two thousand seven hundred eighty-eight children and adolescents aged 2 to 18 years (hereinafter referred to as children) who underwent tonsillectomy with or without adenoidectomy. Interventions: Each child received 1 of 2 distinct intravenous doses of perioperative dexamethasone (0.5 mg/kg or 1.0 mg/kg) based on the protocol of the surgeon who performed the tonsillectomy; other aspects of care, including anesthetic technique, perioperative an-algesia, and postoperative care, were equivalent between children. Main Outcome Measures: Occurrence of postoperative hemorrhage based on 3 severity stratification levels. Results: Ninety-four of the 2788 children experienced 104 episodes of postoperative hemorrhage. After adjusting for age, sex, primary diagnosis, and surgical technique, the odds ratio of experiencing a postoperative hemorrhage of any severity in children who received the 1.0-mg/kg compared with the 0.5-mg/kg dose was 0.66 (95% confidence interval [CI], 0.42-1.05). Children requiring readmission with or without the need for operative intervention demonstrated an adjusted odds ratio of 0.83 (95% Cl, 0.51-1.36). An adjusted odds ratio of 0.71 (95% Cl, 0.39-1.28) was seen in children requiring operative intervention. Conclusion: In this observational review of children undergoing tonsillectomy or adenotonsillectomy, perioperative dexamethasone administration is not associated with a dose-dependent elevation of postoperative hemorrhage rates after adjusting for age, sex, primary diagnosis, and surgical technique. C1 [Brigger, Matthew T.] Naval Med Ctr San Diego, Dept Otolaryngol Head & Neck Surg, San Diego, CA 92134 USA. [Cunningham, Michael J.; Hartnick, Christopher J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Brigger, MT (reprint author), Naval Med Ctr San Diego, Dept Otolaryngol Head & Neck Surg, 34800 Bob Wilson Dr, San Diego, CA 92134 USA. EM matt.brigger@alumni.vanderbilt.edu NR 31 TC 15 Z9 15 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 2010 VL 136 IS 8 BP 766 EP 772 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 640FD UT WOS:000281033300002 PM 20713751 ER PT J AU Kakarala, K Brigger, MT Faquin, WC Hartnick, CJ Cunningham, MJ AF Kakarala, Kiran Brigger, Matthew T. Faquin, William C. Hartnick, Christopher J. Cunningham, Michael J. TI Cystic Pilomatrixoma A Diagnostic Challenge SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID CALCIFYING EPITHELIOMA; BETA-CATENIN; HEAD; NECK; CHILDREN; MUTATION AB Pilomatrixoma is a benign neoplasm of ectodermal hair follicle germinal matrix cell origin. At least 50% of pilomatrixomas are reported to arise in the head and neck, and 40% occur before the age of 10 years.(1-3) Pilomatrixoma is the third most common reason for excision of a cervicofacial mass in children, after lymphadenopathy and epidermoid cysts. C1 [Kakarala, Kiran; Hartnick, Christopher J.; Cunningham, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Kakarala, Kiran; Hartnick, Christopher J.; Cunningham, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brigger, Matthew T.] Naval Med Ctr, Dept Otolaryngol Head & Neck Surg, San Diego, CA USA. RP Kakarala, K (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM kiran_kakarala@meei.harvard.edu OI Kakarala, Kiran/0000-0002-1003-8024 NR 15 TC 3 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 2010 VL 136 IS 8 BP 830 EP 833 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 640FD UT WOS:000281033300015 PM 20713764 ER PT J AU Silver, AL Masia, R Hasserjian, RP Deschler, DG AF Silver, Amanda L. Masia, Ricard Hasserjian, Robert P. Deschler, Daniel G. TI Pathology Quiz Case 1 Diffuse large B-cell lymphoma (DLBCL) SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID CRANIAL NERVE PALSIES; NON-HODGKIN-LYMPHOMA; CENTRAL SKULL BASE; MR C1 [Silver, Amanda L.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Masia, Ricard; Hasserjian, Robert P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Silver, AL (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 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 2010 VL 136 IS 8 BP 840 EP + PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 640FD UT WOS:000281033300019 PM 20713768 ER PT J AU Joehl, RJ AF Joehl, Raymond J. TI Mom Is Not Permitted to Be Ill SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 [Joehl, Raymond J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Surg Serv, Hines, IL 60141 USA. [Joehl, Raymond J.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. RP Joehl, RJ (reprint author), Hines VA Hosp, 5000 S 5th Ave, Hines, IL 60141 USA. EM raymond.joehl@va.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD AUG PY 2010 VL 145 IS 8 BP 780 EP 780 PG 1 WC Surgery SC Surgery GA 640FB UT WOS:000281033000016 PM 20737736 ER PT J AU Napadow, V LaCount, L Park, K As-Sanie, S Clauw, DJ Harris, RE AF Napadow, Vitaly LaCount, Lauren Park, Kyungmo As-Sanie, Sawsan Clauw, Daniel J. Harris, Richard E. TI Intrinsic Brain Connectivity in Fibromyalgia Is Associated With Chronic Pain Intensity SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RESTING-STATE CONNECTIVITY; FUNCTIONAL CONNECTIVITY; SPONTANEOUS FLUCTUATIONS; RESPONSE FUNCTION; DEFAULT NETWORK; WORKING-MEMORY; BOLD SIGNAL; CORTEX; DYNAMICS; TASK AB Objective. Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. The objective of this study was to investigate the degree of connectivity between multiple brain networks in patients with FM, as well as how activity in these networks correlates with the level of spontaneous pain. Methods. Resting-state functional magnetic resonance imaging (FMRI) data from 18 patients with FM and 18 age-matched healthy control subjects were analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic, or resting-state, connectivity was evaluated in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also analyzed for covariance with intrinsic connectivity. Results. Patients with FM had greater connectivity within the DMN and right EAN (corrected P [P(corr)] < 0.05 versus controls), and greater connectivity between the DMN and the insular cortex, which is a brain region known to process evoked pain. Furthermore, greater intensity of spontaneous pain at the time of the FMRI scan correlated with greater intrinsic connectivity between the insula and both the DMN and right EAN (P(corr) < 0.05). Conclusion. These findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in patients with FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay among multiple brain networks. C1 [Napadow, Vitaly] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Napadow, Vitaly] Logan Coll Chiropract, Chesterfield, MO USA. [Park, Kyungmo] Kyung Hee Univ, Yongin, South Korea. [As-Sanie, Sawsan; Clauw, Daniel J.; Harris, Richard E.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Napadow, V (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, 149 13th St 2301, Charlestown, MA 02129 USA. EM vitaly@nmr.mgh.harvard.edu RI Harris, Richard/F-1307-2011 FU NIH (National Center for Complementary and Alternative Medicine) [K01-A002166, R01-AT-004714, F05-AT-003770, P01-AT-002048, K01-AT-01111]; National Center for Research Resources [P41-RR-14075]; GCRC [M01-RR-01066]; Mental Illness and Neuroscience Discovery Institute; Pfizer Inc.; Institute of Information Technology Advancement, Korea [IITA-2008 [C1090-0801-0002]]; US Department of Defense [DAMD-W81XWH-07-2-0050]; Dana Foundation FX Supported by the NIH (National Center for Complementary and Alternative Medicine grants K01-A002166 and R01-AT-004714 [to Dr. Napadow], F05-AT-003770 [to Dr. Park], and P01-AT-002048, K01-AT-01111 [to Dr. Harris], and National Center for Research Resources grants P41-RR-14075 and GCRC M01-RR-01066), the Mental Illness and Neuroscience Discovery Institute, and Pfizer Inc. Dr. Park's work also was supported by the Institute of Information Technology Advancement, Korea (IITA-2008 [C1090-0801-0002]). Dr. Harris' work also was supported by the US Department of Defense (Army grant DAMD-W81XWH-07-2-0050); he is recipient of a Dana Foundation Award in Brain and Immuno-Imaging. NR 50 TC 203 Z9 208 U1 1 U2 31 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD AUG PY 2010 VL 62 IS 8 BP 2545 EP 2555 DI 10.1002/art.27497 PG 11 WC Rheumatology SC Rheumatology GA 661WA UT WOS:000282762100042 PM 20506181 ER PT J AU Liao, KP Cai, TX Gainer, V Goryachev, S Zeng-Treitler, Q Raychaudhuri, S Szolovits, P Churchill, S Murphy, S Kohane, I Karlson, EW Plenge, RM AF Liao, Katherine P. Cai, Tianxi Gainer, Vivian Goryachev, Sergey Zeng-Treitler, Qing Raychaudhuri, Soumya Szolovits, Peter Churchill, Susanne Murphy, Shawn Kohane, Isaac Karlson, Elizabeth W. Plenge, Robert M. TI Electronic Medical Records for Discovery Research in Rheumatoid Arthritis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID HEALTH RECORDS; AUTOMATED IDENTIFICATION; NECROSIS-FACTOR; UNITED-STATES; ANTI-CCP; SENSITIVITY; DIAGNOSIS; RISK; ASSOCIATION; SPECIFICITY C1 [Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gainer, Vivian; Goryachev, Sergey; Churchill, Susanne] Partners Healthcare Syst, Boston, MA USA. [Zeng-Treitler, Qing] Univ Utah, Salt Lake City, UT USA. [Raychaudhuri, Soumya; Plenge, Robert M.] Broad Inst, Cambridge, MA USA. [Szolovits, Peter] MIT, Cambridge, MA 02139 USA. [Murphy, Shawn] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Plenge, RM (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 77 Ave Louis Pasteur,Suite 168, Boston, MA 02115 USA. EM rplenge@partners.org RI Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Szolovits, Peter/0000-0001-8411-6403 FU National Library of Medicine [U54LM008748]; NIH [T32-AR055885, R01-LM007222, R01-DK075837, R01-LM009966, R21-NR0101710-01, R21-NS067463, K08-AR-055688-01A1, UL1-RR02578-01, R01-HL091495-01A1, R01-AR049880, P60-AR047782, K24-AR0524-01, R01-AR057108, R01-AR056768, U54-LM00878]; i2b2 [NIH U54-LM008748] FX Supported by award U54LM008748 from the National Library of Medicine. Dr. Liao's work was supported by the NIH (grant T32-AR055885). Drs. Cai, Goryachev, Szolovits, Churchill, and Kohane's work was supported by the i2b2 grant (NIH U54-LM008748). Dr. Zeng-Treitler's work was supported by the NIH (grants R01-LM007222, R01-DK075837, R01-LM009966, R21-NR0101710-01, and R21-NS067463) and the i2b2 grant (NIH U54-LM008748). Dr. Raychaudhuri's work was supported by the NIH (grant K08-AR-055688-01A1). Dr. Murphy's work was supported by the NIH (grants UL1-RR02578-01 and R01-HL091495-01A1) and the i2b2 grant (NIH U54-LM008748). Dr. Karlson's work was supported by the NIH (grants R01-AR049880, P60-AR047782, and K24-AR0524-01) and the i2b2 grant (NIH U54-LM008748). Dr. Plenge's work was supported by the NIH (grants R01-AR057108, R01-AR056768, and U54-LM00878) and a Career Award for Medical Scientists from the Burroughs Wellcome Fund. NR 34 TC 86 Z9 86 U1 0 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD AUG PY 2010 VL 62 IS 8 BP 1120 EP 1127 DI 10.1002/acr.20184 PG 8 WC Rheumatology SC Rheumatology GA 639NA UT WOS:000280980300009 PM 20235204 ER PT J AU Fitzgerald, ML Mujawar, Z Tamehiro, N AF Fitzgerald, Michael L. Mujawar, Zahedi Tamehiro, Norimasa TI ABC transporters, atherosclerosis and inflammation SO ATHEROSCLEROSIS LA English DT Review DE ABCA1; ABCG1; ABCG5; ABCG8; Tangier disease; Sitosterolemia; Atherosclerosis; Inflammation ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; CORONARY-HEART-DISEASE; REVERSE CHOLESTEROL TRANSPORT; INCREASED SITOSTEROL ABSORPTION; BINDING CASSETTE TRANSPORTER-1; RANDOMIZED CONTROLLED-TRIAL; RECEPTOR-DEFICIENT MICE; ABCG1(-/-) BONE-MARROW; TRANSFER PROTEIN GENE AB Atherosclerosis, driven by inflamed lipid-laden lesions, can occlude the coronary arteries and lead to myocardial infarction. This chronic disease is a major and expensive health burden. However, the body is able to mobilize and excrete cholesterol and other lipids, thus preventing atherosclerosis by a process termed reverse cholesterol transport (RCT). Insight into the mechanism of RCT has been gained by the study of two rare syndromes caused by the mutation of ABC transporter loci. In Tangier disease, loss of ABCA1 prevents cells from exporting cholesterol and phospholipid, thus resulting in the build-up of cholesterol in the peripheral tissues and a loss of circulating HDL. Consistent with HDL being an athero-protective particle, Tangier patients are more prone to develop atherosclerosis. Likewise, sitosterolemia is another inherited syndrome associated with premature atherosclerosis. Here mutations in either the ABCG5 or G8 loci, prevents hepatocytes and enterocytes from excreting cholesterol and plant sterols, including sitosterol, into the bile and intestinal lumen. Thus, ABCG5 and G8, which from a heterodimer, constitute a transporter that excretes cholesterol and dietary sterols back into the gut, while ABCA1 functions to export excess cell cholesterol and phospholipid during the biogenesis of HDL. Interestingly, a third protein, ABCG1, that has been shown to have anti-atherosclerotic activity in mice, may also act to transfer cholesterol to mature HDL particles. Here we review the relationship between the lipid transport activities of these proteins and their anti-atherosclerotic effect, particularly how they may reduce inflammatory signaling pathways. Of particular interest are recent reports that indicate both ABCA1 and ABCG1 modulate cell surface cholesterol levels and inhibit its partitioning into lipid rafts. Given lipid rafts may provide platforms for innate immune receptors to respond to inflammatory signals, it follows that loss of ABCA1 and ABCG1 by increasing raft content will increase signaling through these receptors, as has been experimentally demonstrated. Moreover, additional reports indicate ABCA1, and possibly SR-BI, another HDL receptor, may directly act as anti-inflammatory receptors independent of their lipid transport activities. Finally, we give an update on the progress and pitfalls of therapeutic approaches that seek to stimulate the flux of lipids through the RCT pathway. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Fitzgerald, Michael L.; Mujawar, Zahedi; Tamehiro, Norimasa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA. [Fitzgerald, Michael L.; Mujawar, Zahedi; Tamehiro, Norimasa] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Fitzgerald, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, 185 Cambridge St, Boston, MA 02114 USA. EM mfitzgerald@ccib.mgh.harvard.edu FU NIH-NHLBI; American Heart Association [HL074136, 09GRNT2260352]; Uehara Memorial Foundation; Nagai Foundation of Tokyo; Japan Heart Foundation FX This work was supported by NIH-NHLBI and American Heart Association grants to ML Fitzgerald (HL074136, 09GRNT2260352) and by fellowship training grants from the Uehara Memorial Foundation, the Nagai Foundation of Tokyo and the Japan Heart Foundation (N Tamehiro), the American Heart Association (Z Mujawar). NR 168 TC 86 Z9 98 U1 1 U2 19 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2010 VL 211 IS 2 BP 361 EP 370 DI 10.1016/j.atherosclerosis.2010.01.011 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 634VC UT WOS:000280612700002 PM 20138281 ER PT J AU Blankstein, R Ferencik, M AF Blankstein, Ron Ferencik, Maros TI The vulnerable plaque: Can it be detected with Cardiac CT? SO ATHEROSCLEROSIS LA English DT Editorial Material DE Vulnerable plaque; Cardiac CT; Acute coronary syndrome ID ACUTE CORONARY SYNDROME; MULTISLICE COMPUTED-TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; INTRAVASCULAR ULTRASOUND ANALYSIS; RADIOFREQUENCY DATA-ANALYSIS; STABLE ANGINA-PECTORIS; VIRTUAL HISTOLOGY; ARTERY-DISEASE; PROGNOSTIC VALUE; ATHEROSCLEROTIC PLAQUES C1 [Blankstein, Ron] Harvard Univ, Brigham & Womens Hosp, Sch Med, Noninvas Cardiovasc Imaging Program,Dept Med,Card, Boston, MA 02115 USA. [Ferencik, Maros] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02115 USA. RP Blankstein, R (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Noninvas Cardiovasc Imaging Program,Dept Med,Card, 75 Francis St, Boston, MA 02115 USA. EM rblankstein@partners.org NR 39 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2010 VL 211 IS 2 BP 386 EP 389 DI 10.1016/j.atherosclerosis.2010.06.014 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 634VC UT WOS:000280612700006 PM 20619414 ER PT J AU Damrauer, SM Fisher, MD Wada, H Siracuse, JJ da Silva, CG Moon, K Csizmadia, E Maccariello, ER Patel, VI Studer, P Essayagh, S Aird, WC Daniel, S Ferran, C AF Damrauer, Scott M. Fisher, Mark D. Wada, Hiromi Siracuse, Jeffrey J. da Silva, Cleide G. Moon, Karam Csizmadia, Eva Maccariello, Elizabeth R. Patel, Virendra I. Studer, Peter Essayagh, Sanah Aird, William C. Daniel, Soizic Ferran, Christiane TI A20 inhibits post-angioplasty restenosis by blocking macrophage trafficking and decreasing adventitial neovascularization SO ATHEROSCLEROSIS LA English DT Article DE Neointimal hyperplasia; Vascular endothelial growth factor; Neovascularization; Macrophage ID ENDOTHELIAL GROWTH-FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; FACTOR-KAPPA-B; MUSCLE-CELL PROLIFERATION; INTIMAL HYPERPLASIA; NEOINTIMAL HYPERPLASIA; IN-VITRO; ATHEROSCLEROTIC LESIONS; ADHESION MOLECULE-1; HEMATOPOIETIC STEM AB Objective: Neointimal hyperplasia is an inflammatory and proliferative process that occurs as a result of injury to the vessel wall. We have shown that the homeostatic protein A20 prevents neointimal hyperplasia by affecting endothelial cell (EC) and smooth muscle cell (SMC) responses to injury. In this work, we questioned whether A20 impacts other pathogenic effectors of neointimal hyperplasia including homing of monocyte/macrophages and EC/SMC precursors to the site of vascular injury, vascular endothelial growth factor (VEGF) secretion, and adventitial neovascularization. Methods and results: Carotid balloon angioplasty was performed on rat recipients of a bone marrow transplant from green fluorescent rats. Adenoviral delivery of A20 prevented neointimal hyperplasia and decreased macrophage infiltration. This was associated with decreased ICAM-1 and MCP-1 expression in vitro. Additionally, A20 reduced neovascularization in the adventitia of balloon injured carotid arteries, which correlated with fewer VEGF positive cells. Conclusions: A20 downregulates adhesion markers, chemokine production, and adventitial angiogenesis, all of which are required for macrophage trafficking to sites of vascular injury. This, in turn, diminishes the inflammatory milieu to prevent neointimal hyperplasia. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Ferran, Christiane] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res,Div Vasc Surg, Boston, MA 02215 USA. [Wada, Hiromi; Aird, William C.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Mol Med, Boston, MA 02215 USA. [Ferran, Christiane] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Transplant Inst, Boston, MA 02215 USA. [Ferran, Christiane] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Nephrol,Dept Med, Boston, MA 02215 USA. [Damrauer, Scott M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Ferran, C (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res,Div Vasc Surg, RN 370F G,99 Brookline Ave, Boston, MA 02215 USA. EM cferran@caregroup.harvard.edu OI Moon, Karam/0000-0002-7984-5801 FU NIH [RO1 HL080130, RO1 DK063275, RO1 HL57791, T32 HL07734]; Juvenile Diabetes Research Foundation [1-2007-567] FX This research was supported by NIH grant RO1 HL080130 and in part by NIH grants RO1 DK063275, RO1 HL57791, Juvenile Diabetes Research Foundation grant 1-2007-567 to CF. SMD, MDF, JJS, and VIP were supported by NIH T32 HL07734. NR 32 TC 12 Z9 13 U1 0 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2010 VL 211 IS 2 BP 404 EP 408 DI 10.1016/j.atherosclerosis.2010.03.029 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 634VC UT WOS:000280612700011 PM 20430393 ER PT J AU Otto, MW McHugh, RK Simon, NM Farach, FJ Worthington, JJ Pollack, MH AF Otto, Michael W. McHugh, R. Kathryn Simon, Naomi M. Farach, Frank J. Worthington, John J. Pollack, Mark H. TI Efficacy of CBT for benzodiazepine discontinuation in patients with panic disorder: Further evaluation SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Benzodiazepines; Panic disorder; Cognitive behavior therapy; Drug withdrawal ID COGNITIVE-BEHAVIORAL THERAPY; ALPRAZOLAM DISCONTINUATION; PHARMACOLOGICAL TREATMENT; ANXIETY DISORDER; FOLLOW-UP; WITHDRAWAL; METAANALYSIS; TRIAL; AGORAPHOBIA; DEPRESSION AB Despite its acute efficacy for the treatment of panic disorder, benzodiazepines (BZs) are associated with a withdrawal syndrome that closely mimics anxiety sensations, leading to difficulty with treatment discontinuation and often disorder relapse. An exposure-based cognitive-behavioral treatment for BZ discontinuation, Panic Control Treatment for BZ Discontinuation (CBT) targets the fear of these sensations and has demonstrated efficacy in preventing disorder relapse and facilitating successful BZ discontinuation among patients with panic disorder. In this randomized controlled trial, CBT was compared to taper alone and a taper plus a relaxation condition to control for the effect of therapist contact and support among 47 patients with panic disorder seeking taper from BZs. Based on the primary outcome of successful discontinuation of BZ use, results indicate that adjunctive CBT provided additive benefits above both taper alone and taper plus relaxation, with consistently medium and large effect sizes over time that reached significance at the six month follow-up evaluation. The efficacy of CBT relative to either of the other taper conditions reflected very large and significant effect sizes at that time. These findings suggest that CBT provides specific efficacy for the successful discontinuation from BZs, even when controlling for therapist contact and relaxation training. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Otto, Michael W.] Boston Univ, Ctr Anxiety & Related Disorders, Dept Psychol, Boston, MA 02215 USA. [Simon, Naomi M.; Farach, Frank J.; Worthington, John J.; Pollack, Mark H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Otto, MW (reprint author), Boston Univ, Ctr Anxiety & Related Disorders, Dept Psychol, 648 Beacon St,6th Floor,5th Floor, Boston, MA 02215 USA. EM mwotto@bu.edu OI McHugh, R. Kathryn/0000-0002-3011-8697; Farach, Frank/0000-0002-2145-0145 FU NIDA NIH HHS [R10 DA009692] NR 51 TC 23 Z9 23 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD AUG PY 2010 VL 48 IS 8 BP 720 EP 727 DI 10.1016/j.brat.2010.04.002 PG 8 WC Psychology, Clinical SC Psychology GA 641CP UT WOS:000281102400005 PM 20546699 ER PT J AU Forcione, DG Brugge, WR AF Forcione, David G. Brugge, William R. TI New kid on the block? Autoimmune pancreatitis SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Article ID LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; IMMUNOGLOBULIN G4-ASSOCIATED CHOLANGITIS; IDIOPATHIC CHRONIC-PANCREATITIS; IGG4-RELATED SYSTEMIC-DISEASE; HELICOBACTER-PYLORI INFECTION; PRIMARY SJOGRENS-SYNDROME; OF-THE-LITERATURE; DIAGNOSTIC-CRITERIA; STEROID-THERAPY; CARBONIC-ANHYDRASE C1 [Forcione, David G.; Brugge, William R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM wbrugge@partners.org NR 125 TC 6 Z9 7 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6918 EI 1532-1916 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD AUG PY 2010 VL 24 IS 4 BP 361 EP 378 DI 10.1016/j.bpg.2010.04.002 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 670AN UT WOS:000283392300002 PM 20833341 ER PT J AU Lansdorp-Vogelaar, I Knudsen, AB Brenner, H AF Lansdorp-Vogelaar, Iris Knudsen, Amy B. Brenner, Hermann TI Cost-effectiveness of colorectal cancer screening - An overview SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Article DE Colorectal neoplasms; Mass screening; Cost-benefit analysis; Occult blood; Colonoscopy; Sigmoidoscopy; Colonography, Computed tomographic; Stool DNA; Capsule endoscopy ID FECAL-OCCULT-BLOOD; SERVICES TASK-FORCE; COLON-CANCER; FLEXIBLE SIGMOIDOSCOPY; PERSONALIZED MEDICINE; IMMUNOCHEMICAL TEST; CAPSULE ENDOSCOPY; CT COLONOGRAPHY; DETECTION RATES; UNITED-STATES AB There are several modalities available for a colorectal cancer (CRC) screening program. When determining which CRC screening program to implement, the costs of such programs should be considered in comparison to the health benefits they are expected to provide. Cost-effectiveness analysis provides a tool to do this. In this paper we review the evidence on the cost-effectiveness of CRC screening. Published studies universally indicate that when compared with no CRC screening, all screening modalities provide additional years of life at a cost that is deemed acceptable by most industrialized nations. Many recent studies even find CRC screening to be cost-saving. However, when the alternative CRC screening strategies are compared against each other in an incremental cost-effectiveness analysis, no single optimal strategy emerges across the studies. There is consensus that the new technologies of stool DNA testing, computed tomographic colonography and capsule endoscopy are not yet cost-effective compared with the established CRC screening tests. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Lansdorp-Vogelaar, Iris] Erasmus MC, Univ Med Ctr, Dept Publ Hlth, NL-3000 CA Rotterdam, Netherlands. [Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69115 Heidelberg, Germany. RP Lansdorp-Vogelaar, I (reprint author), Erasmus MC, Univ Med Ctr, Dept Publ Hlth, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM i.vogelaar@erasmusmc.nl; aknudsen@mgh-ita.org; h.brenner@Dkfz-Heidelberg.de RI Brenner, Hermann/B-4627-2017 OI Brenner, Hermann/0000-0002-6129-1572 FU National Cancer Institute [U01-CA-097426, U01-CA-115953, U01-CA-088204] FX Drs. Lansdorp-Vogelaar and Knudsen are supported in part by Cancer Intervention and Surveillance Modeling Network grants from the National Cancer Institute: (U01-CA-097426 (Lansdorp-Vogelaar), U01-CA-115953 (Lansdorp-Vogelaar), and U01-CA-088204 (Knudsen)). NR 91 TC 21 Z9 22 U1 1 U2 8 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6918 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD AUG PY 2010 VL 24 IS 4 BP 439 EP 449 DI 10.1016/j.bpg.2010.04.004 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 670AN UT WOS:000283392300009 PM 20833348 ER PT J AU Wheeler, JM Guthrie, CR Kraemer, BC AF Wheeler, Jeanna M. Guthrie, Chris R. Kraemer, Brian C. TI The role of MSUT-2 in tau neurotoxicity: a target for neuroprotection in tauopathy? SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE aggresome; Alzheimer's disease; neurodegeneration; neurofibrillary tangle; protein aggregation; tau ID CAENORHABDITIS-ELEGANS; PROTEIN AGGREGATION; AGGRESOME FORMATION; MISFOLDED PROTEINS; MISSENSE MUTATIONS; FTDP-17 MUTATIONS; POLYADENOSINE RNA; DEMENTIA FTDP-17; INCLUSION-BODIES; MOUSE MODEL AB We previously developed a transgenic Caenorhabditis elegons model of human tauopathy disorders by expressing human tau in nematode worm neurons to explore genetic pathways contributing to tau-induced neurodegeneration. This animal model recapitulates several hallmarks of human tauopathies, including altered behaviour, accumulation of detergent-insoluble phosphorylated tau protein and neurodegeneration. To identify genes required for tau neurotoxicity, we carried out a forward genetic screen for mutations that suppress tau neurotoxicity. We ultimately cloned the sut-2 (suppressor of tau pathology-2) gene, mutations in which alleviate tau neurotoxicity in C. elegons. SUT-2 encodes a novel subtype of CCCH zinc-finger protein conserved across animal phyla. SUT-2 shares significant identity with the mammalian SUT-2 (MSUT-2). We identified components of the aggresome as binding partners of MSUT-2. Thus we hypothesize that MSUT-2 plays a role in the formation and/or clearance of protein aggregates. We are currently exploring the role of MSUT-2 in tauopathy using mammalian systems. The identification of sut-2 as a gene required for tau neurotoxicity in C. elegons suggests new neuroprotective strategies targeting MSUT-2 that may be effective in modulating tau neurotoxicity in human tauopathy disorders. C1 [Kraemer, Brian C.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Gerontol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Geriatr Med, Seattle, WA 98195 USA. RP Kraemer, BC (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle Div, 1660 S Colombian Way, Seattle, WA 98108 USA. EM kraemerb@u.washington.edu FU Department of Veterans Affairs; National Institute of Neurological Disorders and Stroke [R01NS064131] FX This work was Supported by a Department of Veterans Affairs Merit Review Grant and by the National Institute of Neurological Disorders and Stroke [grant number R01NS064131 (to B.C.K.)]. NR 39 TC 6 Z9 7 U1 1 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD AUG PY 2010 VL 38 BP 973 EP 976 DI 10.1042/BST0380973 PN 4 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 636QL UT WOS:000280753600021 PM 20658987 ER PT J AU Merkulova, M Bakulina, A Thaker, YR Gruber, G Marshansky, V AF Merkulova, Maria Bakulina, Anastasia Thaker, Youg Raj Grueber, Gerhard Marshansky, Vladimir TI Specific motifs of the V-ATPase a2-subunit isoform interact with catalytic and regulatory domains of ARNO SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article DE V-type ATPase; Arf-GEF ARNO; Sec7-domain; PB-domain; BIAcore; NMR; Peptide structure; Phosphorylation ID VACUOLAR H+-ATPASE; NUCLEOTIDE EXCHANGE FACTORS; RENAL TUBULAR-ACIDOSIS; A-SUBUNIT; PROTON PUMP; ARF; YEAST; PHYSIOLOGY; ALDOLASE; FAMILY AB We have previously shown that the V-ATPase a2-subunit isoform interacts specifically, and in an intra-endosomal acidification-dependent manner, with the Arf-GEF ARNO. In the present study, we examined the molecular mechanism of this interaction using synthetic peptides and purified recombinant proteins in protein-association assays. In these experiments, we revealed the involvement of multiple sites on the N-terminus of the V-ATPase a2-subunit (a2N) in the association with ARNO. While six a2N-derived peptides interact with wild-type ARNO, only two of them (named a2N-01 and a2N-03) bind to its catalytic Sec7-domain. However, of these, only the a2N-01 peptide (MGSLFRSESMCLAQLFL) showed specificity towards the Sec7-domain compared to other domains of the ARNO protein. Surface plasmon resonance kinetic analysis revealed a very strong binding affinity between this a2N-01 peptide and the Sec7-domain of ARNO, with dissociation constant K(D) = 3.44 x 10(-7) M. similar to the K(D) = 3.13 x 10(-7) M binding affinity between wild-type a2N and the full-length ARNO protein. In further pull-down experiments, we also revealed the involvement of multiple sites on ARNO itself in the association with a2N. However, while its catalytic Sec7-domain has the strongest interaction, the PH-, and PB-domains show much weaker binding to a2N. Interestingly, an interaction of the a2N to a peptide corresponding to ARNO's PB-domain was abolished by phosphorylation of ARNO residue Ser(392). The 3D-structures of the non-phosphorylated and phosphorylated peptides were resolved by NMR spectroscopy, and we have identified rearrangements resulting from Ser(392) phosphorylation. Homology modeling suggests that these alterations may modulate the access of the a2N to its interaction pocket on ARNO that is formed by the Sec7 and PB-domains. Overall, our data indicate that the interaction between the a2-subunit of V-ATPase and ARNO is a complex process involving various binding sites on both proteins. Importantly, the binding affinity between the a2-subunit and ARNO is in the same range as those previously reported for the intramolecular association of subunits within V-ATPase complex itself, indicating an important cell biological role for the interaction between the V-ATPase and small GTPase regulatory proteins. (C) 2010 Elsevier B.V. All rights reserved. C1 [Marshansky, Vladimir] Massachusetts Gen Hosp, CPZN, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Merkulova, Maria; Marshansky, Vladimir] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. [Merkulova, Maria; Marshansky, Vladimir] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bakulina, Anastasia] State Res Ctr Virol & Biotechnol VECTOR, Koltsov 630559, Novosibirsk Reg, Russia. [Thaker, Youg Raj; Grueber, Gerhard] Nanyang Technol Univ, Div Struct & Computat Biol, Sch Biol Sci, Singapore 637551, Singapore. [Grueber, Gerhard] Bioinformat Inst ASTAR, Singapore 138671, Singapore. RP Marshansky, V (reprint author), Massachusetts Gen Hosp, CPZN, Ctr Syst Biol, Program Membrane Biol, 185 Cambridge St,Suite 8212, Boston, MA 02114 USA. EM Vladimir_Marshansky@hms.harvard.edu RI Bakulina, Anastasia/A-6215-2014; Thaker, Youg/K-6083-2016; OI thaker, youg/0000-0002-6496-1017 FU National Institutes of Health (NIH) [DK038452]; Boston Area Diabetes Endocrinology Research Center (BADERC) [DK057521-08]; School of Biological Sciences, Nanyang Technological University (NTU) [SUG/31/05] FX We would like to thank Dr. Dennis Brown and Dr. Masamitsu Futai for the critical reading and constructive suggestions during the preparation of this manuscript. We also would like to thank Dr. Ashok Khatri, (Director of Partners/MGH Peptide/Protein Core Facility) for the assistance with peptide synthesis. We are grateful to Dr. James Casanova for his generous gift of the cDNA construct of human ARNO. We are also grateful to S. Gayen, School of Biological Sciences, NTU, for the assistance in generating the NMR related figures. This study was supported by a National Institutes of Health (NIH) grant DK038452 and by Boston Area Diabetes Endocrinology Research Center (BADERC) grant DK057521-08 (to VM) as well as by the School of Biological Sciences, Nanyang Technological University (NTU) grant SUG/31/05 (to GG). Y.R. Thaker is grateful to the authority of NTU for awarding a research scholarship. NR 50 TC 20 Z9 20 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD AUG PY 2010 VL 1797 IS 8 BP 1398 EP 1409 DI 10.1016/j.bbabio.2010.02.009 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 625IM UT WOS:000279888700006 PM 20153292 ER PT J AU Bhattacharyya, R Kovacs, DM AF Bhattacharyya, Raja Kovacs, Dora M. TI ACAT inhibition and amyloid beta reduction SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE Alzheimer's disease; A beta; ACAT; Cholesterol; Cholesteryl ester; Lipid droplet ID A-CHOLESTEROL ACYLTRANSFERASE; LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY ATHEROSCLEROSIS; DOMINANT-NEGATIVE MUTANT; TRANSGENIC MOUSE MODEL; MAMMALIAN ACYL-COA; ALZHEIMERS-DISEASE; LIPID DROPLETS; PRECURSOR PROTEIN; APOLIPOPROTEIN-E AB Alzheimer's disease (AD) is a devastating neurodegenerative disorder. Accumulation and deposition of the beta-amyloid (A beta) peptide generated from its larger amyloid precursor protein (APP) is one of the pathophysiological hallmarks of AD. Intracellular cholesterol was shown to regulate A beta production. Recent genetic and biochemical studies indicate that not only the amount, but also the distribution of intracellular cholesterol is critical to regulate A beta generation. Acyl-coenzyme A: cholesterol acyl-transferase (ACAT) is a family of enzymes that regulates the cellular distribution of cholesterol by converting membrane cholesterol into hydrophobic cholesteryl esters for cholesterol storage and transport. Using pharmacological inhibitors and transgenic animal models, we and others have identified ACAT1 as a potential therapeutic target to lower A beta generation and accumulation. Here we discuss data focusing on ACAT inhibition as an effective strategy for the prevention and treatment of AD. (C) 2010 Elsevier B.V. All rights reserved. C1 [Bhattacharyya, Raja; Kovacs, Dora M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Dis Lab,Genet & Aging Res Unit,MIND, Charlestown, MA 02129 USA. RP Kovacs, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurobiol Dis Lab,Genet & Aging Res Unit,MIND, Charlestown, MA 02129 USA. EM dora_kovacs@hms.harvard.edu FU Cure Alzheimer's Fund; U.S. National Institutes of Health [R01 NS45860] FX This study was supported by grants from the Cure Alzheimer's Fund (D.M.K.) and the U.S. National Institutes of Health (R01 NS45860; D.M.K.). NR 112 TC 29 Z9 29 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD AUG PY 2010 VL 1801 IS 8 SI SI BP 960 EP 965 DI 10.1016/j.bbalip.2010.04.003 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 620CG UT WOS:000279476000028 PM 20398792 ER PT J AU Dominy, JE Lee, Y Gerhart-Hines, Z Puigserver, P AF Dominy, John E., Jr. Lee, Yoonjin Gerhart-Hines, Zachary Puigserver, Pere TI Nutrient-dependent regulation of PGC-1 alpha's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5 SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Review DE PGC-1 alpha; GCN5; Sirt1; Acetylation ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; HEPATIC GLUCOSE-PRODUCTION; PPAR-GAMMA COACTIVATOR-1; NAD(+) SALVAGE PATHWAY; FATTY-ACID OXIDATION; RECEPTOR-GAMMA; DEACETYLASE SIRT1; MODULATES GLUCONEOGENESIS; MITOCHONDRIAL-FUNCTION; INSULIN SENSITIVITY AB Mammals possess an intricate regulatory system for controlling flux through fuel utilization pathways in response to the dietary availability of particular macronutrients. Under fasting conditions, for instance, mammals initiate a whole body metabolic response that limits glucose utilization and favors fatty acid oxidation. Understanding the underlying mechanisms by which this process occurs will facilitate the development of new treatments for metabolic disorders such as type II diabetes and obesity. One of the recently identified components of the signal transduction pathway involved in metabolic reprogramming is PGC-1 alpha. This transcriptional coactivator is able to coordinate the expression of a wide array of genes involved in glucose and fatty acid metabolism. The nutrient-mediated control of PGC-1 alpha activity is tightly correlated with its acetylation state. In this review, we evaluate how the nutrient regulation of PGC-1 alpha activity squares with the regulation of its acetylation state by the deacetylase Sirt1 and the acetyltransferase GCN5. We also propose an outline of additional experimental directives that will help to shed additional light on this very powerful transcriptional coactivator. (C) 2009 Elsevier B.V. All rights reserved. C1 [Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM pere_puigserver@dfci.harvard.edu FU NIDDK NIH HHS [R01 DK069966, R01 DK069966-01A1, R01 DK069966-02, R01 DK069966-03, R01 DK069966-04, R01 DK069966-05] NR 70 TC 74 Z9 77 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD AUG PY 2010 VL 1804 IS 8 SI SI BP 1676 EP 1683 DI 10.1016/j.bbapap.2009.11.023 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 621JA UT WOS:000279571200014 PM 20005308 ER PT J AU Wang, J Fivecoat, H Ho, L Pan, Y Ling, E Pasinetti, GM AF Wang, Jun Fivecoat, Hayley Ho, Lap Pan, Yong Ling, Emi Pasinetti, Giulio Maria TI The role of Sirt1: At the crossroad between promotion of longevity and protection against Alzheimer's disease neuropathology SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Review DE Sirtuins; Caloric restriction; Neurodegeneration; Alzheimer's disease; Dementia ID CALORIC RESTRICTION; LIFE-SPAN; SACCHAROMYCES-CEREVISIAE; AMYLOID NEUROPATHOLOGY; MOUSE MODEL; MECHANISM; PROTEIN; DEACETYLATION; NICOTINAMIDE; YEAST AB Sirt1, a mammalian member of the sirtuin gene family, holds great potential for promoting longevity, preventing against disease and increasing cell survival. For example, studies suggest that the beneficial impact of caloric restriction in promoting longevity and cellular function may be mediated, in part, by Sirt1 through mechanisms involving PGC-1 alpha, which plays important role in the regulation of cellular metabolism and inflammatory and antioxidant responses. Sirt1 may also interfere with mechanisms implicated in pathological disorders. We will present recent evidence indicating that Sirt1 may protect against Alzheimer's disease by interfering with the generation of beta-amyloid peptides. We will discuss Sirt1 as a potential novel target, in addition to the development of Sirt1 activators for the prevention and treatment of Alzheimer's disease. Published by Elsevier B.V. C1 [Wang, Jun; Fivecoat, Hayley; Ho, Lap; Pan, Yong; Ling, Emi; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol,Brain Inst, Ctr Excellence Novel Approaches Neurodiagnost & N, Ctr Excellence Res Complementary & Alternat Med A, New York, NY 10029 USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, GRECC, Biomed Res & Training Program, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol,Brain Inst, Ctr Excellence Novel Approaches Neurodiagnost & N, Ctr Excellence Res Complementary & Alternat Med A, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU Atkins Foundation FX The studies reported in this review article were generously supported by the Atkins Foundation. NR 38 TC 38 Z9 42 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD AUG PY 2010 VL 1804 IS 8 SI SI BP 1690 EP 1694 DI 10.1016/j.bbapap.2009.11.015 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 621JA UT WOS:000279571200016 PM 19945548 ER PT J AU Hook, V Hook, G Kindy, M AF Hook, Vivian Hook, Gregory Kindy, Mark TI Pharmacogenetic features of cathepsin B inhibitors that improve memory deficit and reduce beta-amyloid related to Alzheimer's disease SO BIOLOGICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 6th General Meeting of the International-Proteolysis-Society CY OCT 26-30, 2009 CL Gold Coast, AUSTRALIA SP Int Proteolysis Soc DE Alzheimer's disease; beta-amyloid; cathepsin B; cleavage site; inhibitor; memory; pharmacogenetics; protease; transgenic AD mice ID REGULATED SECRETORY VESICLES; PRECURSOR PROTEIN; TRANSGENIC MICE; WILD-TYPE; IN-VIVO; SELECTIVE INHIBITOR; CHROMAFFIN CELLS; THERAPEUTICS; PEPTIDES; BACE1 AB Beta-amyloid (A beta) in the brain is a major factor involved in Alzheimer's disease (AD) that results in severe memory deficit. Our recent studies demonstrate pharmacogenetic differences in the effects of inhibitors of cathepsin B to improve memory and reduce A beta in different mouse models of AD. The inhibitors improve memory and reduce brain A beta in mice expressing the wild-type (WT) beta-secretase site of human APP, expressed in most AD patients. However, these inhibitors have no effect in mice expressing the rare Swedish (Swe) mutant amyloid precursor protein (APP). Knockout of the cathepsin B decreased brain A beta in mice expressing WT APP, validating cathepsin B as the target. The specificity of cathepsin B to cleave the WT beta-secretase site, but not the Swe mutant site, of APP for A beta production explains the distinct inhibitor responses in the different AD mouse models. In contrast to cathepsin B, the BACE1 beta-secretase prefers to cleave the Swe mutant site. Discussion of BACE1 data in the field indicate that they do not preclude cathepsin B as also being a beta-secretase. Cathepsin B and BACE1 could participate jointly as beta-secretases. Significantly, the majority of AD patients express WT APP and, therefore, inhibitors of cathepsin B represent candidate drugs for AD. C1 [Hook, Vivian] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Hook, Vivian] Univ Calif San Diego, Dept Neurosci, Sch Med, La Jolla, CA 92093 USA. [Hook, Vivian] Univ Calif San Diego, Dept Pharmacol, Sch Med, La Jolla, CA 92093 USA. [Hook, Vivian] Univ Calif San Diego, Dept Med, Sch Med, La Jolla, CA 92093 USA. [Hook, Gregory] Amer Life Sci Pharmaceut Inc, San Diego, CA 92109 USA. [Kindy, Mark] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Kindy, Mark] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Hook, V (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. EM vhook@ucsd.edu FU NIA NIH HHS [R21 AG027446, R44 AG032784, R44 AG030865, 1R44AG032784]; NIDA NIH HHS [R01 DA004271] NR 47 TC 16 Z9 18 U1 2 U2 7 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD AUG PY 2010 VL 391 IS 8 BP 861 EP 872 DI 10.1515/BC.2010.110 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 642HL UT WOS:000281198700004 PM 20536395 ER PT J AU Alyea, EP DeAngelo, DJ Moldrem, J Pagel, JM Przepiorka, D Sadelin, M Young, JW Giralt, S Bishop, M Riddell, S AF Alyea, Edwin P. DeAngelo, Daniel J. Moldrem, Jeffrey Pagel, John M. Przepiorka, Donna Sadelin, Michel Young, James W. Giralt, Sergio Bishop, Michael Riddell, Stan TI NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematologic Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic cell transplantation; Relapse prevention; Acute graft-versus-host disease; Immunotherapy; Resistant leukemia ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; HUMAN T-CELLS; ANTIGEN-PRESENTING CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; TOTAL-BODY IRRADIATION; REDUCED-INTENSITY TRANSPLANTATION AB Prevention of relapse after allogeneic hematopoietic stem cell transplantation is the most likely approach to improve survival of patients treated for hematologic malignancies. Herein we review the limits of currently available transplant therapies and the innovative strategies being developed to overcome resistance to therapy or to fill therapeutic modalities not currently available. These novel strategies include nonimmunologic therapies, such as targeted preparative regimens and posttransplant drug therapy, as well as immunologic interventions, including graft engineering, donor lymphocyte infusions, T cell engineering, vaccination, and dendritic cell-based approaches. Several aspects of the biology of the malignant cells as well as the host have been identified that obviate success of even these newer strategies. To maximize the potential for success, we recommend pursuing research to develop additional targeted therapies to be used in the preparative regimen or as maintenance posttransplant, better characterize the T cell and dendritic cells subsets involved in graft-versus-host disease and the graft-versus-leukemia/tumor effect, identify strategies for timing immunologic or nonimmunologic therapies to eliminate the noncycling cancer stem cell, identify more targets for immunotherapies, develop new vaccines that will not be limited by HLA, and develop methods to identify populations at very high risk for relapse to accelerate clinical development and avoid toxicity in patients not at risk for relapse. Biol Blood Marrow Transplant 16: 1037-1069 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Alyea, Edwin P.; DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moldrem, Jeffrey; Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Pagel, John M.; Riddell, Stan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Pagel, John M.; Riddell, Stan] Univ Washington, Seattle, WA 98195 USA. [Przepiorka, Donna] US FDA, Rockville, MD 20857 USA. [Sadelin, Michel; Young, James W.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bishop, Michael] NCI, Bethesda, MD 20892 USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM edwin_alyea@dfci.harvard.edu FU NCI NIH HHS [P01 CA018029, P01 CA018029-36] NR 280 TC 23 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2010 VL 16 IS 8 BP 1037 EP 1069 DI 10.1016/j.bbmt.2010.05.005 PG 33 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 628RH UT WOS:000280137800002 PM 20580849 ER PT J AU Schriber, J Agovi, MA Ho, V Ballen, KK Bacigalupo, A Lazarus, HM Bredeson, CN Gupta, V Maziarz, RT Hale, GA Litzow, MR Logan, B Bornhauser, M Giller, RH Isola, L Marks, DI Rizzo, JD Pasquini, MC AF Schriber, Jeffrey Agovi, Manza-A Ho, Vincent Ballen, Karen K. Bacigalupo, Andrea Lazarus, Hillard M. Bredeson, Christopher N. Gupta, Vikas Maziarz, Richard T. Hale, Gregory A. Litzow, Mark R. Logan, Brent Bornhauser, Martin Giller, Roger H. Isola, Luis Marks, David I. Rizzo, J. Douglas Pasquini, Marcelo C. TI Second Unrelated Donor Hematopoietic Cell Transplantation for Primary Graft Failure SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Graft failure; Second transplant; Nonengraftment ID BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; APLASTIC-ANEMIA; BLOOD; FLUDARABINE; REJECTION; RISK AB Failure to engraft donor cells is a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We describe the results of 122 patients reported to the National Marrow Donor Program between 1990 and 2005, who received a second unrelated donor HCT after failing to achieve an absolute neutrophil count of >= 500/mu L without recurrent disease. Patients were transplanted for leukemia (n = 83), myelodysplastic disorders (n = 16), severe aplastic anemia (n = 20), and other diseases (n = 3). The median age was 29 years. Twenty-four patients received second grafts from a different unrelated donor. Among 98 patients who received a second graft from the same donor, 28 received products that were previously collected and cryopreserved for the first transplantation. One-year overall survival (OS) after second transplant was 11%, with 10 patients alive at last follow-up. We observed no differences between patients who received grafts from the same or different donors, or in those who received fresh or cryopreserved product. The outcomes after a second allogeneic HCT for primary graft failure are dismal. Identifying risk factors for primary graft failure can decrease the incidence of this complication. Further studies are needed to test whether early recognition and hastened procurement of alternative grafts can improve transplant outcomes for primary graft failure. Biol Blood Marrow Transplant 16: 1099-1106 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Agovi, Manza-A; Logan, Brent; Rizzo, J. Douglas; Pasquini, Marcelo C.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Schriber, Jeffrey] Banner Blood Marrow Transplant Program, Phoenix, AZ USA. [Schriber, Jeffrey] City Hope Banner, Phoenix, AZ USA. [Ho, Vincent] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bacigalupo, Andrea] Osped San Martino Genova, Genoa, Italy. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Bredeson, Christopher N.] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Milwaukee, WI 53226 USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Hale, Gregory A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Bornhauser, Martin] Univ Klinikum Carl Gustav Carus, Dresden, Germany. [Giller, Roger H.] Univ Colorado, Childrens Hosp, Aurora, CO USA. [Isola, Luis] Mt Sinai Hosp, New York, NY 10029 USA. [Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England. RP Pasquini, MC (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite CC5500, Milwaukee, WI 53226 USA. EM mpasquin@mcw.edu RI Bornhauser, Martin/F-8101-2010 FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung, and Blood Institute (NHLBI) [5U01HL069294]; National Institute of Allergy and Infectious Diseases (NIAID); Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech, an Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); 2 Grants, N00014-06-1-0704 and N00014-08-1-0058, from the Office of Naval Research; and grants from AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech, an Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck & Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. NR 19 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2010 VL 16 IS 8 BP 1099 EP 1106 DI 10.1016/j.bbmt.2010.02.013 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 628RH UT WOS:000280137800007 PM 20172038 ER PT J AU Cutler, C Kim, HT Ayanian, S Bradwin, G Revta, C Aldridge, J Ho, V Alyea, E Koreth, J Armand, P Soiffer, R Ritz, J Richardson, PG Antin, JH AF Cutler, Corey Kim, Haesook T. Ayanian, Shake Bradwin, Gary Revta, Carolyn Aldridge, Julie Ho, Vincent Alyea, Edwin Koreth, John Armand, Philippe Soiffer, Robert Ritz, Jerome Richardson, Paul G. Antin, Joseph H. TI Prediction of Veno-Occlusive Disease Using Biomarkers of Endothelial Injury SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Veno-occlusive disease; Endothelium; Sirolimus ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; VON-WILLEBRAND-FACTOR; THROMBOTIC MICROANGIOPATHY; GROWTH-FACTOR; SIROLIMUS; LIVER; DEFIBROTIDE; PARAMETERS; MARKERS AB Predicting the development of veno-occlusive disease (VOD) of the liver remains challenging. We hypothesized that biomarkers of endothelial injury in myeloablative allogeneic transplantation recipients could predict VOD occurrence. We evaluated 4 biomarkers-von Willebrand Factor (vWF), thrombomodulin, E-selectin, and soluble intercellular adhesion molecule-1 (sICAM-1)-weekly in the peritransplantation period in an attempt to predict VOD. In the patients who received sirolimus, vWF, thrombomodulin, and sICAM-1 levels were significantly elevated in patients with VOD compared with those without VOD on day - 1 (P <= .035), day +7 (P <= .0001), and day +14 (P <= .004). E-selectin was predictive on day +7 (P = .007). Levels of vWF >= 1400 IU/mL and thrombomodulin >= 100 ng/mL on day +7 were both 100% sensitive and 100% specific in predicting VOD. These biomarkers were informative when adjusted for other risk factors for VOD in regression analysis. Among patients not receiving sirolimus, biomarkers of endothelial injury were not informative. We conclude that vWF, thrombomodulin, and sICAM-1 elevations before and early after transplantation may be useful in predicting VOD in patients receiving sirolimus. Biol Blood Marrow Transplant 16: 1180-1185 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Cutler, Corey; Revta, Carolyn; Ho, Vincent; Alyea, Edwin; Koreth, John; Armand, Philippe; Soiffer, Robert; Ritz, Jerome; Richardson, Paul G.; Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Oncol, Boston, MA 02115 USA. [Kim, Haesook T.; Aldridge, Julie] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Ayanian, Shake; Bradwin, Gary] Childrens Hosp Boston, Boston, MA 02115 USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Oncol, 44 Binney St,D1B13, Boston, MA 02115 USA. EM corey_cutler@dfci.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU Ted and Eileen Pasquarello Research Fund; National Institutes of Health [AI29530, CA142106, HL070149]; Stem Cell Cyclists of the Pan-Mass Challenge FX This work was supported by the Ted and Eileen Pasquarello Research Fund and National Institutes of Health Grants AI29530, CA142106, and HL070149. Corey Cutler is supported by the Stem Cell Cyclists of the Pan-Mass Challenge. NR 23 TC 24 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD AUG PY 2010 VL 16 IS 8 BP 1180 EP 1185 DI 10.1016/j.bbmt.2010.02.016 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 628RH UT WOS:000280137800017 PM 20184961 ER PT J AU Moskowitz, JS Blaisse, MR Samuel, RE Hsu, HP Harris, MB Martin, SD Lee, JC Spector, M Hammond, PT AF Moskowitz, Joshua S. Blaisse, Michael R. Samuel, Raymond E. Hsu, Hu-Ping Harris, Mitchel B. Martin, Scott D. Lee, Jean C. Spector, Myron Hammond, Paula T. TI The effectiveness of the controlled release of gentamicin from polyelectrolyte multilayers in the treatment of Staphylococcus aureus infection in a rabbit bone model SO BIOMATERIALS LA English DT Article DE Antibacterial; Animal model; Bone; Controlled drug release; Layer-by-layer; Coating ID LAYER THIN-FILMS; IN-VIVO; EXPONENTIAL-GROWTH; POLY(ACRYLIC ACID); DRUG-RELEASE; PLASMID DNA; PMMA BEADS; OSTEOMYELITIS; IMPLANTS; COATINGS AB While the infection rate of orthopedic implants is low, the required treatment, which can involve six weeks of antibiotic therapy and two additional surgical operations, is life threatening and expensive, and thus motivates the development of a one-stage re-implantation procedure. Polyelectrolyte multilayers incorporating gentamicin were fabricated using the layer-by-layer deposition process for use as a device coating to address an existing bone infection in a direct implant exchange operation. The films eluted about 70% of their payload in vitro during the first three days and subsequently continued to release drug for more than four additional weeks, reaching a total average release of over 550 mu g/cm(2). The coatings were demonstrated to be bactericidal against Staphylococcus aureus, and degradation products were generally nontoxic towards MC3T3-E1 murine preosteoblasts. Film-coated titanium implants were compared to uncoated implants in an in vivo S. aureus bone infection model. After a direct exchange procedure, the antimicrobial-coated devices yielded bone homogenates with a significantly lower degree of infection than uncoated devices at both day four (p < 0.004) and day seven (p < 0.03). This study has demonstrated that a self-assembled ultrathin film coating is capable of effectively treating an experimental bone infection in vivo and lays the foundation for development of a multi-therapeutic film for optimized, synergistic treatment of pain, infection, and osteomyelitis. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Moskowitz, Joshua S.; Blaisse, Michael R.; Samuel, Raymond E.; Hammond, Paula T.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Hsu, Hu-Ping; Spector, Myron] VA Boston Healthcare Syst, Tissue Engn Labs, Boston, MA 02130 USA. [Hsu, Hu-Ping; Harris, Mitchel B.; Martin, Scott D.; Spector, Myron] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Hsu, Hu-Ping; Harris, Mitchel B.; Martin, Scott D.; Lee, Jean C.; Spector, Myron] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lee, Jean C.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. RP Hammond, PT (reprint author), 77 Massachusetts Ave,Room 66-352, Cambridge, MA 02139 USA. EM hammond@mit.edu FU National Institutes of Health, National Institute of Aging [5R01AG029601-03] FX This work was financially supported by the National Institutes of Health, National Institute of Aging (5R01AG029601-03). We thank Catrina Wong, Alison Hayward, DVM, and Alison Darby, DVM (animal support staff. Division of Comparative Medicine, MIT) for care, handling, and anesthesia of animals, Ellen Buckley and Nikki Lew (microbiologists, Division of Comparative Medicine, MIT) for blood analyses, cultures, and biofilm studies, Wayne Schwark, DVM, PhD (Professor of Pharmacology, Department of Molecular Medicine, Cornell University), for gentamicin assays, and Helen Chuang, PhD (Research Scientist, ChromoLogic, Pasadena, CA), for consultation on in vitro film studies. The authors greatly appreciate the use of equipment available at the Institute for Soldier Nanotechnologies (ISN), as well as the Robert Langer Laboratory for scintillation counting, the Center for Materials Science and Engineering for profilometry, and the Division of Comparative Medicine's animal facilities for all in vivo work. NR 52 TC 63 Z9 66 U1 5 U2 44 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD AUG PY 2010 VL 31 IS 23 BP 6019 EP 6030 DI 10.1016/j.biomaterials.2010.04.011 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 623DZ UT WOS:000279719600013 PM 20488534 ER PT J AU Felts, AS Lindsley, SR Lamb, JP Rodriguez, AL Menon, UN Jadhav, S Jones, CK Conn, PJ Lindsley, CW Emmitte, KA AF Felts, Andrew S. Lindsley, Stacey R. Lamb, Jeffrey P. Rodriguez, Alice L. Menon, Usha N. Jadhav, Satyawan Jones, Carrie K. Conn, P. Jeffrey Lindsley, Craig W. Emmitte, Kyle A. TI 3-Cyano-5-fluoro-N-arylbenzamides as negative allosteric modulators of mGlu(5): Identification of easily prepared tool compounds with CNS exposure in rats SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE mGlu5; GPCR; Allosteric modulator; CNS; GERD; Fragile X syndrome; Addiction; PD-LID ID MGLUR5 ANTAGONIST MPEP; METABOTROPIC GLUTAMATE-RECEPTOR-5 ANTAGONIST; RECEPTOR SUBTYPE-5 ANTAGONISTS; CUE-INDUCED REINSTATEMENT; GLUTAMATE RECEPTORS; GASTROESOPHAGEAL-REFLUX; SQUIRREL-MONKEYS; SEEKING BEHAVIOR; COCAINE SEEKING; POTENT AB Development of SAR in a 3-cyano-5-fluoro-N-arylbenzamide series of non-competitive antagonists of mGlu(5) using a functional cell-based assay is described in this Letter. Further characterization of selected potent compounds in in vitro assays designed to measure their metabolic stability and protein binding is also presented. Subsequent evaluation of two new compounds in pharmacokinetic studies using intraperitoneal dosing in rats demonstrated good exposure in both plasma and brain samples. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Felts, Andrew S.; Lindsley, Stacey R.; Lamb, Jeffrey P.; Rodriguez, Alice L.; Menon, Usha N.; Jadhav, Satyawan; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Felts, Andrew S.; Lindsley, Stacey R.; Lamb, Jeffrey P.; Rodriguez, Alice L.; Menon, Usha N.; Jadhav, Satyawan; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A.] Vanderbilt Univ, Med Ctr, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA. [Jones, Carrie K.; Lindsley, Craig W.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Jones, Carrie K.] Tennesse Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37212 USA. RP Emmitte, KA (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. EM kyle.a.emmitte@Vanderbilt.edu RI Conn, Peter/D-7848-2012 FU NIDA [RO1 DA023947-01]; Seaside Therapeutics [VUMC33842] FX We thank NIDA (RO1 DA023947-01) and Seaside Therapeutics (VUMC33842) for their support of our programs in the development of non-competitive antagonist of mGlu5. Matt Mulder, Chris Denicola, and Sichen Chang are also thanked for the purification of compounds using the mass-directed HPLC system. NR 48 TC 17 Z9 17 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 1 PY 2010 VL 20 IS 15 BP 4390 EP 4394 DI 10.1016/j.bmcl.2010.06.064 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 625BK UT WOS:000279866300020 PM 20598884 ER PT J AU Reilly-Harrington, NA DeBonis, D Leon, AC Sylvia, L Perlis, R Lewis, D Sachs, GS AF Reilly-Harrington, Noreen A. DeBonis, Daniel Leon, Andrew C. Sylvia, Louisa Perlis, Roy Lewis, Daniel Sachs, Gary S. TI The interactive computer interview for mania SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; computerized interviews; rater reliability ID SAMPLE-SIZE REQUIREMENTS; CLINICAL-TRIALS; MEASUREMENT ERROR; DEPRESSION; EFFICACY; AGREEMENT; VALIDITY; DESIGN AB Objectives: The Interactive Computer Interview for Mania (ICI-M) is a computer-administered interview that presents probes to assess symptom severity and utilizes a scoring algorithm to select follow-up questions and rate subject responses in accordance with rating scale anchor points. The current study examines the acceptability, feasibility, and reliability of the ICI-M as a potential method for evaluating the performance of human raters. Methods: Participants with a diagnosis of bipolar I or II disorder completed both a live interview of the Young Mania Rating Scale with a human rater (LR) and the ICI-M. A panel of three expert raters reviewed each videotaped LR and assigned a consensus rating (CR). Participants completed a modified version of the Client Satisfaction Questionnaire to assess each method. Results: Intraclass correlation coefficients were 0.91 between the ICI-M and CR and 0.97 between the LR and CR (n = 100), providing empirical support for the inter-rater reliability of each approach. Coefficient alphas indicated comparable internal consistency reliability: ICI-M = 0.82, LR = 0.83, and CR = 0.84. The ICI-M was significantly more sensitive in detecting symptomatology than the LR (p < 0.001) and the CR (p < 0.001), and resulted in significantly higher ratings than CR on mood, speech, psychotic content, and disruptive-aggressive behavior. While participants endorsed significantly higher overall satisfaction with LR, no significant differences emerged between ICI-M and LR regarding willingness to participate again or ability to understand the questions. Conclusions: The ICI-M is a well-accepted and reliable method for assessing manic symptoms. The ICI-M is a tool with adequate sensitivity to elicit symptoms and rate severity and is recommended as a tool to monitor and improve rater performance, not as a replacement of a human rater. C1 [Reilly-Harrington, Noreen A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Reilly-Harrington, Noreen A.; DeBonis, Daniel; Sylvia, Louisa; Perlis, Roy; Lewis, Daniel; Sachs, Gary S.] Concordant Rater Syst, Boston, MA USA. [Reilly-Harrington, Noreen A.; Sylvia, Louisa; Perlis, Roy; Sachs, Gary S.] Harvard Univ, Sch Med, Boston, MA USA. [Leon, Andrew C.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Reilly-Harrington, NA (reprint author), Massachusetts Gen Hosp, Bipolar Clin, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM nhreilly@partners.org FU NIMH [1 R43 MH65796-01A1]; AstraZeneca; Eli Lilly Co.; Pfizer; GlaxoSmithKline; Bristol-Myers Squibb FX This study was funded by NIMH Grant 1 R43 MH65796-01A1 to NAR-H, Principal Investigator.; NAR-H is a shareholder and consultant for Concordant Rater Systems and receives royalties from Oxford University Press and the American Psychological Association. DD is president and shareholder of Concordant Rater Systems. ACL serves on the Data and Safety Monitoring Boards for AstraZeneca, Dainippon Sumitomo Pharma America, and Pfizer; has served as a consultant/advisor to the FDA, NIMH, Cyberonics, MedAvante, Schering Plough, and Takeda; and has equity in MedAvante. LS is a consultant for Concordant Rater Systems. RP has received speaker's fees/honoraria from AstraZeneca, Eli Lilly & Co., Pfizer, GlaxoSmithKline, and Bristol-Myers Squibb; has served on the consulting/advisory boards for AstraZeneca, Eli Lilly & Co., Pfizer, Bristol-Myers Squibb, and Proteus LLC; and has received royalties from Concordant Rater Systems. DL is a shareholder in Concordant Rater Systems. GSS serves on the speakers bureaus of Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Co., GlaxoSmithKline, Janssen, Memory Pharmaceuticals, Novartis, Pfizer, Sanofi-aventis, and Wyeth; serves as an advisory board member or consultant for Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, CNS Response, Concordant Rater Systems, Elan Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Janssen, Memory Pharmaceuticals, Merck, Novartis, Organon, Otsuka, Pfizer, Repligen, Sanofi-aventis, Schering Plough, Sepracor, Shire, Sigma-Tau, Solvay Pharmaceuticals, and Wyeth; and his spouse holds shares in Concordant Rater Systems. NR 22 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2010 VL 12 IS 5 BP 521 EP 527 DI 10.1111/j.1399-5618.2010.00844.x PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 639PX UT WOS:000280987800007 PM 20712753 ER PT J AU Altshuler, LL Abulseoud, OA Foland-Ross, L Bartzokis, G Chang, S Mintz, J Hellemann, G Vinters, HV AF Altshuler, Lori L. Abulseoud, Osama A. Foland-Ross, Lara Bartzokis, George Chang, Sean Mintz, Jim Hellemann, Gerhard Vinters, Harry V. TI Amygdala astrocyte reduction in subjects with major depressive disorder but not bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE amygdala; astrocyte; bipolar disorder; depression; glial cell; neuron ID MAGNETIC-RESONANCE SPECTROSCOPY; DORSOLATERAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; FIBRILLARY ACIDIC PROTEIN; TEMPORAL-LOBE STRUCTURES; GAMMA-AMINOBUTYRIC-ACID; GLIAL-CELL DENSITY; MOOD DISORDERS; NEUROPATHOLOGY CONSORTIUM; GLUTAMINE-SYNTHETASE AB Objectives: Several magnetic resonance imaging studies have found changes in amygdala volumes in adults with mood disorders. The cellular basis for these changes has not been explored in detail. Specifically, it is not known whether differences in the density and/or volume of neurons or glial cells contribute to tissue volume changes seen on magnetic resonance images. Methods: Postmortem amygdala samples were obtained from the Stanley Foundation Neuropathology Consortium from subjects diagnosed with bipolar disorder (n = 10), major depressive disorder (n = 11), and schizophrenia (n = 9), and from normal controls (n = 14). Samples were first stained with glial fibrillary acidic protein (GFAP) and counter-stained with hematoxylin to ascertain neuron and glia (astrocyte) densities. Results: No significant differences in neuronal densities were found between groups. However, a reduction in the density of GFAP immunoreactive astrocytes was observed in the amygdala of subjects with major depressive disorder compared to the bipolar disorder, schizophrenia, and normal control postmortem samples. Conclusions: A decrease in density of GFAP immunoreactive astrocytes in the amygdala of depressed subjects is consistent with prior histologic reports and might contribute to amygdala volume reductions reported in several in vivo neuroimaging studies. C1 [Altshuler, Lori L.; Bartzokis, George; Hellemann, Gerhard] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Altshuler, Lori L.; Bartzokis, George; Mintz, Jim] VA Greater Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA USA. [Abulseoud, Osama A.] Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [Foland-Ross, Lara; Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Lab Neuroimaging, Dept Neurol,Div Brain Mapping, Los Angeles, CA 90095 USA. [Chang, Sean] Albert Einstein Jacobi Med Ctr, Dept Radiol, Bronx, NY USA. [Vinters, Harry V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Vinters, Harry V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 1544,Box 6, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu RI Bartzokis, George/K-2409-2013 FU Stanley Medical Research Institute (Bethesda, MD, USA); Daljit S. and Elaine Sarkaria Chair in Diagnostic Medicine; Janssen FX Postmortem brain tissue was donated by the Stanley Medical Research Institute's brain collection. Financial support for this research was provided by the Stanley Medical Research Institute (Bethesda, MD, USA). HHV is supported in part by the Daljit S. and Elaine Sarkaria Chair in Diagnostic Medicine. We are grateful to Arnold Scheibel for consultation regarding identification of amygdala nuclei, and to Teri English for editorial assistance.; LLA is on the scientific advisory board for Forest Laboratories (for matters related to s-citalopram). GB has received grant support from Janssen and is on the speakers bureaus for and receives honoraria from Pfizer and Novartis, none for matters related to bipolar disorder. HVV has stock holdings in the following pharmaceutical companies: Pfizer, GlaxoSmithKline Beecham, and Teva. All authors report that they do not have any conflict of interest relevant to this manuscript. NR 72 TC 46 Z9 47 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2010 VL 12 IS 5 BP 541 EP 549 DI 10.1111/j.1399-5618.2010.00838.x PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 639PX UT WOS:000280987800010 PM 20712756 ER PT J AU Cipriano, LE Barth, WH Zaric, GS AF Cipriano, L. E. Barth, W. H., Jr. Zaric, G. S. TI The cost-effectiveness of targeted or universal screening for vasa praevia at 18-20 weeks of gestation in Ontario SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Cost effectiveness analysis; prenatal diagnosis; screening; ultrasonography; ultrasound; vasa praevia ID UMBILICAL-CORD; COLOR DOPPLER; VELAMENTOUS INSERTION; PRENATAL-DIAGNOSIS; ULTRASOUND; TECHNOLOGY; SONOGRAPHY; GUIDELINES AB Objectives To estimate the cost-effectiveness of targeted and universal screening for vasa praevia at 18-20 weeks of gestation in singleton and twin pregnancies. Design Cost-utility analysis based on a decision-analytic model comparing relevant strategies and life-long outcomes for mother and infant(s). Setting Ontario, Canada. Population A cohort of pregnant women in 1 year. Methods We constructed a decision-analytic model to estimate the lifetime incremental costs and benefits of screening for vasa praevia. Inputs were estimated from the literature. Costs were collected from the London Health Sciences Centre, the Ontario Health Insurance Program, and other sources. We used one-way, scenario and probabilistic sensitivity analysis to determine the robustness of the results. Main outcome measures Incremental costs, life expectancy, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER). Results Universal transvaginal ultrasound screening of twin pregnancies has an ICER of $5488 per QALY-gained. Screening all singleton pregnancies with the risk factors low-lying placentas, in vitro fertilisation (IVF) conception, accessory placental lobes, or velamentous cord insertion has an ICER of $15,764 per QALY-gained even though identifying some of these risk factors requires routine use of colour Doppler during transabdominal examinations. Screening women with a marginal cord insertion costs an additional $27,603 per QALY-gained. Universal transvaginal screening for vasa praevia in singleton pregnancies costs $579,164 per QALY compared with targeted screening. Conclusions Compared with current practice, screening all twin pregnancies for vasa praevia with transvaginal ultrasound is cost-effective. Among the alternatives considered, the use of colour Doppler at all transabdominal ultrasound examinations of singleton pregnancies and targeted use of transvaginal ultrasound for IVF pregnancies or when the placenta has been found to be associated with one or more risk factors is cost-effective. Universal screening of singleton pregnancies is not cost-effective compared with targeted screening. C1 [Zaric, G. S.] Univ Western Ontario, Richard Ivey Sch Business, London, ON N6A 3K7, Canada. [Cipriano, L. E.] Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA. [Barth, W. H., Jr.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Boston, MA 02114 USA. [Barth, W. H., Jr.] Harvard Univ, Sch Med, Boston, MA USA. RP Zaric, GS (reprint author), Univ Western Ontario, Richard Ivey Sch Business, 1151 Richmond St N, London, ON N6A 3K7, Canada. EM gzaric@ivey.uwo.ca RI Zaric, Gregory/B-7665-2013; Cipriano, Lauren/C-3521-2017 OI Cipriano, Lauren/0000-0001-5568-4516 FU Natural Science and Engineering Research Council of Canada (NSERC) FX This work was funded by the Natural Science and Engineering Research Council of Canada (NSERC). NR 33 TC 12 Z9 12 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD AUG PY 2010 VL 117 IS 9 BP 1108 EP 1118 DI 10.1111/j.1471-0528.2010.02621.x PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 620WN UT WOS:000279532500011 PM 20560948 ER PT J AU Araldi, E Schipani, E AF Araldi, Elisa Schipani, Ernestina TI Hypoxia, HIFs and bone development SO BONE LA English DT Article DE Chondrocyte; Osteoblast; Hypoxia; HIF-1alpha; HIF-2alpha ID ARTICULAR CHONDROCYTE PHENOTYPE; INDUCIBLE FACTOR 1-ALPHA; CELL-CYCLE ARREST; GROWTH-PLATE; TRANSCRIPTIONAL ACTIVITY; GENE-EXPRESSION; DISTRACTION OSTEOGENESIS; MICRORNA TARGETS; LYSYL OXIDASE; STEM-CELLS AB Oxygen is not only an obviously important substrate, but it is also a regulatory signal that controls expression of a specific genetic program. Crucial mediator of the adaptive response of cells to hypoxia is the family of Hypoxia-inducible Transcription Factors (HIFs). The fetal growth plate, which is an avascular structure of mesenchymal origin, has a unique out-in gradient of oxygenation. HIF-1 alpha is necessary for chondrogenesis in vivo by controlling a complex homeostatic response that allows chondrocytes to survive and differentiate in a hypoxic environment. Moreover. HIFs are also essential in osteogenesis and joint development. This brief Perspective summarizes the critical role of HIFs in endochondral bone development. (C) 2010 Elsevier Inc. All rights reserved. C1 [Schipani, Ernestina] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schipani, E (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM schipani@helix.mgh.harvard.edu FU NIH [RO1 AR048191 -06] FX This paper was supported by NIH RO1 AR048191 -06 to E.S. NR 111 TC 50 Z9 53 U1 2 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD AUG PY 2010 VL 47 IS 2 BP 190 EP 196 DI 10.1016/j.bone.2010.04.606 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 632SW UT WOS:000280449300003 PM 20444436 ER PT J AU Sahyoun, CP Belliveau, JW Mody, M AF Sahyoun, Cherif P. Belliveau, John W. Mody, Maria TI White matter integrity and pictorial reasoning in high-functioning children with autism SO BRAIN AND COGNITION LA English DT Article DE High-functioning autism; Pictorial reasoning; Language; White matter ID SUPERIOR TEMPORAL GYRUS; SPECTRUM DISORDERS; WORKING-MEMORY; SENTENCE COMPREHENSION; CORPUS-CALLOSUM; FRONTAL-CORTEX; DIFFUSION; LANGUAGE; BRAIN; CONNECTIVITY AB The current study investigated the neurobiological role of white matter in visuospatial versus linguistic processing abilities in autism using diffusion tensor imaging. We examined differences in white matter integrity between high-functioning children with autism (HFA) and typically developing controls (CTRL), in relation to the groups' response times (RT) on a pictorial reasoning task under three conditions: visuospatial, V. semantic. S, and V + S. a hybrid condition allowing language use to facilitate visuospatial transformations. Diffusion-weighted images were collected from HFA and CTRL participants, matched on age and IQ and significance maps were computed for group differences in fractional anisotropy (FA) and in RT-FA association for each condition. Typically developing children showed increased FA within frontal white matter and the superior longitudinal fasciculus (SLF). HFA showed increased FA within peripheral white matter, including the ventral temporal lobe. Additionally, RT-FA relationships in the semantic condition (5) implicated white matter near the STG and in the SLF within the temporal and frontal lobes to a greater extent in CTRL Performance in visuospatial reasoning (V, V + S), in comparison, was related to peripheral parietal and superior precentral white matter in HFA, but to the SLF, callosal, and frontal white matter in CTRL Our results appear to support a preferential use of linguistically-mediated pathways in reasoning by typically developing children, whereas autistic cognition may rely more on visuospatial processing networks. (C) 2010 Elsevier Inc. All rights reserved. C1 [Sahyoun, Cherif P.; Mody, Maria] Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Sahyoun, CP (reprint author), Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, 149 13th St, Charlestown, MA 02129 USA. EM cherif@mit.edu; maria@nmr.mgh.harvard.edu FU National Institutes of Health [NS037462, HD40712]; National Center for Research Resources [P41RR14075] FX This research was supported by funding from the National Institutes of Health (NS037462; HD40712) and in part by the National Center for Research Resources (P41RR14075). We would like to thank all the children and parents for their willingness to participate in the study. We thank Seppo Ahlfors, Douglas Greve, Saad Jbabdi, Shira Schwartz, and Isabelle Soulieres for various aspects of analysis and interpretation. NR 78 TC 28 Z9 28 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD AUG PY 2010 VL 73 IS 3 BP 180 EP 188 DI 10.1016/j.bandc.2010.05.002 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 627DV UT WOS:000280020300005 PM 20542370 ER PT J AU Lin, NU AF Lin, Nancy U. TI Concordance of HER2 in primary tumor and leptomeningeal metastases: now what? SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Editorial Material ID NERVOUS-SYSTEM METASTASES; BREAST-CANCER; MENINGEAL CARCINOMATOSIS; INTRATHECAL TRASTUZUMAB; BRAIN METASTASES; MET; RESISTANCE; EXPRESSION; SURVIVAL; SITES C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM nlin@partners.org NR 27 TC 5 Z9 5 U1 0 U2 0 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 AUG PY 2010 VL 123 IS 1 BP 129 EP 131 DI 10.1007/s10549-009-0720-7 PG 3 WC Oncology SC Oncology GA 627SP UT WOS:000280063200014 PM 20054640 ER PT J AU Gunnarsdottir, KA Jensen, MB Zahrieh, D Gelber, RD Knoop, A Bonetti, M Mouridsen, H Ejlertsen, B AF Gunnarsdottir, Katrin A. Jensen, Maj-Britt Zahrieh, David Gelber, Richard D. Knoop, Ann Bonetti, Marco Mouridsen, Henning Ejlertsen, Bent TI CEF is superior to CMF for tumours with TOP2A aberrations: a Subpopulation Treatment Effect Pattern Plot (STEPP) analysis on Danish Breast Cancer Cooperative Group Study 89D SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; TOP2A; Treatment; Anthracycline; STEPP ID TOPOISOMERASE-II-ALPHA; TREATMENT-COVARIATE INTERACTIONS; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; PREDICTIVE MARKERS; RANDOMIZED-TRIAL; CYCLOPHOSPHAMIDE; METHOTREXATE; FLUOROURACIL; DOXORUBICIN AB The aim of this study was to examine TOP2A gene copy number changes as a means to identify groups of breast cancer patients with superior benefit from treatment with anthracyclines. Tumour tissue was retrospectively collected and successfully analysed for TOP2A in 773 of 980 Danish patients randomly assigned to receive intravenous CMF (cyclophosphamide, methotrexate and fluorouracil) or CEF (cyclophosphamide, epirubicin and fluorouracil) in DBCG trial 89D. Subgroup analyses on this material published by Knoop et al. (J Clin Oncol 23:7483-7490, 2005) and updated by Nielsen et al. (Acta Oncol 47:725-734, 2008) demonstrated that superiority of CEF over CMF is limited to patients with TOP2A aberrations, defined as patients whose tumours have TOP2A ratio below 0.8 or above 2.0. The Subpopulation Treatment Effect Pattern Plot (STEPP) technique was applied to these data to explore the pattern of treatment effect relative to TOP2A and to compare that pattern to the ranges previously used to define 'aberrations'. The pattern of treatment effect illustrated by the STEPP analysis confirmed that the superiority of CEF over CMF is indeed limited to patients whose tumours have high or low TOP2A ratios. The hypothesis of no treatment effect-covariate interaction was rejected (P = 0.02). Furthermore, results indicated that the interval of TOP2A ratios hitherto denoted as 'normal' could be narrower than previously assumed. A more optimal separation of TOP2A subgroups could be obtained by altering cut-points currently used to define TOP2A amplified and TOP2A deleted tumours by narrowing the TOP2A normal interval, and consequently enlarging the population with TOP2A aberrated tumours. C1 [Gunnarsdottir, Katrin A.; Jensen, Maj-Britt; Knoop, Ann; Mouridsen, Henning; Ejlertsen, Bent] Rigshosp, Danish Breast Canc Cooperat Grp DBCG, DBCG Secretariat, DK-2100 Copenhagen, Denmark. [Zahrieh, David; Gelber, Richard D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bonetti, Marco] Bocconi Univ, Milan, Italy. RP Jensen, MB (reprint author), Rigshosp, Danish Breast Canc Cooperat Grp DBCG, DBCG Secretariat, Bldg 2501,9 Blegdamsvej, DK-2100 Copenhagen, Denmark. EM mj@dbcg.dk RI Knoop, Ann/L-7436-2016; OI Knoop, Ann/0000-0003-2898-1093; Bonetti, Marco/0000-0003-2304-4180 FU United States National Cancer Institute [CA-75362] FX This study was supported in part by Grant No. CA-75362 from the United States National Cancer Institute. NR 24 TC 10 Z9 10 U1 0 U2 2 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 AUG PY 2010 VL 123 IS 1 BP 163 EP 169 DI 10.1007/s10549-010-0931-y PG 7 WC Oncology SC Oncology GA 627SP UT WOS:000280063200019 PM 20464479 ER PT J AU Paridaens, RJ Gelber, S Cole, BF Gelber, RD Thurlimann, B Price, KN Holmberg, SB Crivellari, D Coates, AS Goldhirsch, A AF Paridaens, Robert J. Gelber, Shari Cole, Bernard F. Gelber, Richard D. Thuerlimann, Beat Price, Karen N. Holmberg, Stig B. Crivellari, Diana Coates, Alan S. Goldhirsch, Aron TI Adjuvant (c) Online estimation of chemotherapy effectiveness when added to ovarian function suppression plus tamoxifen for premenopausal women with estrogen-receptor-positive breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Adjuvant (c); Online; Estrogen receptor; Premenopausal; Chemotherapy; Endocrine therapy; International Breast Cancer Study Group ID RANDOMIZED-TRIALS; THERAPY; CYCLOPHOSPHAMIDE; FLUOROURACIL; METHOTREXATE; GOSERELIN; SURVIVAL; BLOCKADE; PROGRAM AB Adjuvant!(A (c)) Online (Adjuvant!) is a user-friendly, web-based tool that provides estimates of adjuvant therapy outcomes for individual patients. While reliable evidence underpins estimates for most patient cohorts, there is a paucity of data on the effect of adding chemotherapy to complete estrogen blockade for premenopausal women with estrogen-receptor positive breast cancer. International Breast Cancer Study Group (IBCSG) Trial 11-93 enrolled 174 premenopausal women with estrogen-receptor positive, node-positive breast cancer. Among these patients, 55% had one positive axillary lymph node and 97% had three or fewer positive nodes. Patients were randomized to receive ovarian function suppression plus 5 years of tamoxifen with or without anthracycline-based chemotherapy. Estimated hazard rates and corresponding 10-year relapse-free survival percentages obtained from Trial 11-93 data were compared with those predicted using Adjuvant!. The 10-year relapse-free survival percentages predicted from Adjuvant! were 64.4% (95% CI, 61.9-67.2%) for endocrine therapy alone and 74.9% (95% CI, 73.1-76.8%) for chemoendocrine therapy. By contrast, these estimates in Trial 11-93 were 76.4% (95% CI, 65.8-84.0%) for endocrine therapy alone and 74.9% (95% CI, 64.5-82.7%) for chemoendocrine therapy. The Adjuvant! estimate for the endocrine-alone control group is lower than that observed in Trial 11-93 (P = 0.03), while the estimates for the two chemoendocrine therapy groups are similar. Adjuvant! appears to underestimate the effectiveness of adjuvant endocrine therapy alone for premenopausal women with endocrine responsive breast cancer, thus overestimating the added benefit, if any, from chemotherapy for this patient population. C1 [Paridaens, Robert J.] Catholic Univ Louvain, Univ Hosp Gasthuisberg, Dept Med Oncol, B-3000 Louvain, Belgium. [Gelber, Shari; Cole, Bernard F.; Gelber, Richard D.; Price, Karen N.] IBCSG Stat Ctr, Dana Farber Canc Inst, Boston, MA USA. [Gelber, Shari; Gelber, Richard D.; Price, Karen N.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Cole, Bernard F.] Univ Vermont, Dept Math & Stat, Coll Engn & Math Sci, Burlington, VT 05405 USA. [Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Thuerlimann, Beat] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Holmberg, Stig B.] Sahlgrens Univ Hosp, Dept Surg, Gothenburg, Sweden. [Crivellari, Diana] Ctr Riferimento Oncol, Aviano, Italy. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland. RP Paridaens, RJ (reprint author), Catholic Univ Louvain, Univ Hosp Gasthuisberg, Dept Med Oncol, Herestr 49, B-3000 Louvain, Belgium. EM robert.paridaens@uz.kuleuven.ac.be; shari@jimmy.harvard.edu; ccole@cems.uvm.edu; gelber@jimmy.harvard.edu; beat.thuerlimann@kssg.ch; price@jimmy.harvard.edu; stig.holmberge@vgregion.se; dcrivellari@cro.it; alan.coates@ibcsg.org; aron.goldhirsch@ibcsg.org FU International Breast Cancer Study Group (IBCSG); Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (NHMRC) [940892]; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Research of Eastern Switzerland (OSKK); United States National Cancer Institute [CA-75362] FX The International Breast Cancer Study Group (IBCSG) funded this research. The IBCSG is funded by the Swedish Cancer Society; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (NHMRC grant number 940892); The Frontier Science and Technology Research Foundation, the Swiss Group for Clinical Cancer Research (SAKK); Cancer Research Switzerland/Oncosuisse, the Foundation for Clinical Research of Eastern Switzerland (OSKK); and the United States National Cancer Institute (CA-75362). We thank Love Nickerson for collecting information on patient population from Adjuvant(C) Online. NR 18 TC 12 Z9 12 U1 0 U2 1 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 AUG PY 2010 VL 123 IS 1 BP 303 EP 310 DI 10.1007/s10549-010-0794-2 PG 8 WC Oncology SC Oncology GA 627SP UT WOS:000280063200036 PM 20195744 ER PT J AU Richardson, PG Badros, AZ Jagannath, S Tarantolo, S Wolf, JL Albitar, M Berman, D Messina, M Anderson, KC AF Richardson, Paul G. Badros, Ashraf Z. Jagannath, Sundar Tarantolo, Stefano Wolf, Jeffrey L. Albitar, Maher Berman, David Messina, Marianne Anderson, Kenneth C. TI Tanespimycin with bortezomib: activity in relapsed/refractory patients with multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE tanespimycin; bortezomib; HSP90; HSP70; peripheral neuropathy ID HEAT-SHOCK PROTEINS; PHASE-I TRIAL; ADVANCED CANCER; REFRACTORY MYELOMA; ADULT PATIENTS; HSP90; DEXAMETHASONE; COMBINATION; THERAPY; 17-(ALLYLAMINO)-17-DEMETHOXYGELDANAMYCIN AB P>Tanespimycin (17-allylamino-17-demethoxygeldanamycin, 17-AAG) disrupts heat shock protein 90 (HSP90), a key molecular chaperone for signal transduction proteins critical to myeloma growth, survival and drug resistance. In previous studies, tanespimycin monotherapy was well tolerated and active in heavily pretreated patients with relapsed/refractory multiple myeloma (MM). Preclinical data have shown antitumour synergy between tanespimycin and bortezomib, with more pronounced intracellular accumulation of ubiquitinated proteins than either drug alone, an effect attributed to the synergistic suppression of chymotryptic activity in the 20S proteasome. HSP70 induction has been observed in all Phase 1 tanespimycin studies in which it has been measured, with several separate reports of HSP70 overexpression protecting against peripheral nerve injury. In this Phase 2, open-label multicentre study, we compared 1 center dot 3 mg/m2 bortezomib + three doses of tanespimycin: 50, 175 and 340 mg/m2 in heavily pretreated patients with relapsed and refractory MM and measured HSP70 expression and proteasome activity levels in plasma of treated patients. The study was closed prematurely for resource-based reasons, precluding dose comparison. Nonetheless, antitumour activity was observed, with promising response rates and promising severity of peripheral neuropathy. C1 [Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Badros, Ashraf Z.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Jagannath, Sundar] St Vincents Comprehens Canc Ctr, New York, NY USA. [Wolf, Jeffrey L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Albitar, Maher] Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA. [Berman, David] Bristol Myers Squibb Co, Princeton, NJ USA. [Messina, Marianne] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. 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; Millennium Pharmaceuticals; Celgene Corporation; Novartis FX The authors wish to thank all of the patients and their families, and the research nurses, physicians, coordinators, and other staff at the study sites. We would also like to thank Katie Redman for administrative assistance; and Anne Lambert for editorial assistance. This study was sponsored by Bristol-Myers Squibb (and previously Kosan Biosciences).; Conflicts of Interest; Dr. Richardson serves on advisory boards for Millennium Pharmaceuticals and Celgene Corporation and receives research funding from Millennium Pharmaceuticals. Drs. Badros, Jagannath, Tarantolo, Wolf and Albitar have no other relevant conflicts of interest to disclose. Dr. Berman and Ms. Messina are employees of Bristol-Myers Squibb and have no other relevant conflicts of interest to disclose. Dr. Anderson is a consultant and has received honoraria and research funding from Celgene Corporation, Novartis, Millennium Pharmaceuticals, and Bristol-Myers Squibb. NR 43 TC 42 Z9 42 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2010 VL 150 IS 4 BP 428 EP 437 DI 10.1111/j.1365-2141.2010.08264.x PG 10 WC Hematology SC Hematology GA 635AZ UT WOS:000280629300004 PM 20618338 ER PT J AU Richardson, PG Chanan-Khan, AA Alsina, M Albitar, M Berman, D Messina, M Mitsiades, CS Anderson, KC AF Richardson, Paul G. Chanan-Khan, Asher A. Alsina, Melissa Albitar, Maher Berman, David Messina, Marianne Mitsiades, Constantine S. Anderson, Kenneth C. TI Tanespimycin monotherapy in relapsed multiple myeloma: results of a phase 1 dose-escalation study SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Multiple myeloma; tanespimycin; HSP90; HSP70; 17-AAG ID ADVANCED CANCER; I TRIAL; REFRACTORY MYELOMA; ADULT PATIENTS; BORTEZOMIB; 17-(ALLYLAMINO)-17-DEMETHOXYGELDANAMYCIN; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; 17-DEMETHOXYGELDANAMYCIN; 17-ALLYLAMINO; DEXAMETHASONE AB P>Tanespimycin, a heat shock protein 90 (HSP90) inhibitor, induces apoptosis in drug-sensitive and -resistant MM cell lines and in tumour cells from patients with relapsed MM. In this phase 1 dose-escalation study, the safety, plasma pharmacokinetics, and biological/antitumour activity of tanespimycin were evaluated in heavily pretreated patients with relapsed/refractory MM. Tanespimycin (150-525 mg/m2) was given on days 1, 4, 8, and 11 of each 3-week cycle for up to 8 cycles. Non-haematological AEs included diarrhoea (59%), back pain (35%), fatigue (38%), and nausea (35%); haematological AEs included anaemia (24%) and thrombocytopenia (21%). One patient (3%) achieved minimal response (MR), with a progression-free survival (PFS) of 3 months, a 41% decrease from baseline in urine M protein, and a 33% decrease from baseline in serum M protein. Fifteen patients (52%) achieved SD with a median PFS of 2 center dot 1 months; 5/15 had reductions in serum M protein ranging from 7% to 38% and in urine M protein ranging from 6% to 91%. Mean HSP70 levels increased from day 1 h 0 to day 1 h 4 with further increases on day 11 h 0 and day 11 h 4, consistent with a therapeutic treatment effect. Tanespimycin monotherapy was well tolerated and demonstrated activity across all doses tested. C1 [Richardson, Paul G.; Mitsiades, Constantine S.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chanan-Khan, Asher A.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Alsina, Melissa] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Albitar, Maher] Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA. [Berman, David] Bristol Myers Squibb Co, Princeton, NJ USA. [Messina, Marianne] Bristol Myers Squibb Co, Res & Dev, Wallingford, CT 06492 USA. 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; Millennium Pharmaceuticals FX The authors gratefully acknowledge Alison L. Hannah, MD, consultant, for her contributions to the study and study design. The authors would especially like to thank the patients and their families, as well as the research nurses, physicians, coordinators, and other staff at the study sites including: Dana-Farber Cancer Institute; Roswell Park Cancer Institute; H. Lee Moffitt Cancer Center and Research Institute; and Quest Diagnostics Nichols Institute. We would also like to thank Katie Redman for administrative assistance, and Lauren Cerruto and AOI Communications, L. P., for editorial assistance in the preparation of this manuscript. This study was sponsored by Bristol-Myers Squibb (and previously Kosan Biosciences).; Dr. Richardson serves on advisory committees for Millennium Pharmaceuticals and Celgene Corporation and also receives research funding from Millennium Pharmaceuticals. Dr. Chanan-Khan is on a speakers bureau and receives honoraria from Celgene Corporation, ImmunoGen, Inc., and Millennium Pharmaceuticals. Dr. Alsina has received commercial research grants from Millennium Pharmaceuticals and Centocor Ortho Biotech Inc., and is a consultant for Millennium Pharmaceuticals and Celgene Corporation. Dr. Albitar has no other relevant conflicts of interest to disclose. Dr. Berman and Ms. Messina are employees of Bristol-Myers Squibb and have no relevant conflicts of interest to disclose. Dr. Mitsiades is a consultant for Millennium Pharmaceuticals, Novartis, Bristol-Myers Squibb, Merck & Co., Pharmion and Centocor. He receives research funding from OSI Pharmaceuticals, Amgen Pharmaceuticals, AVEO Pharma, EMD Serono, Sunesis Pharmaceuticals, and Gloucester Pharmaceuticals. He has received honoraria from Millennium Pharmaceuticals, Novartis, Bristol-Myers Squibb, Merck & Co., and Pharmion. He receives royalties from patents from PharmaMar. Dr. Anderson is a consultant and has received honoraria and research funding from Celgene Corporation, Novartis, Millennium Pharmaceuticals, and Bristol- Myers Squibb. NR 22 TC 40 Z9 42 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 EI 1365-2141 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2010 VL 150 IS 4 BP 438 EP 445 DI 10.1111/j.1365-2141.2010.08265.x PG 8 WC Hematology SC Hematology GA 635AZ UT WOS:000280629300005 PM 20618337 ER PT J AU Lopez-Posadas, R Ballester, I Mascaraque, C Suarez, MD Zarzuelo, A Martinez-Augustin, O de Medina, FS AF Lopez-Posadas, R. Ballester, I. Mascaraque, C. Suarez, M. D. Zarzuelo, A. Martinez-Augustin, O. Sanchez de Medina, F. TI Flavonoids exert distinct modulatory actions on cyclooxygenase 2 and NF-kappa B in an intestinal epithelial cell line (IEC18) SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE flavonoids; cyclooxygenase 2; NF-kappa B; intestinal epithelial cells ID INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE-RECEPTORS; EXPERIMENTAL COLITIS; GENE-EXPRESSION; ACID; MACROPHAGES; QUERCETIN; COLON; RAT; PHOSPHORYLATION AB Background and purpose: Cyclooxygenase 2 (COX-2) is involved in inflammatory bowel disease, but the effect of flavonoids at the intestinal epithelial level is unknown. We aimed to characterize the effect and structure-activity relationship of nine selected flavonoids on COX-2 expression in intestinal epithelial cell (IEC)18 cells. We also investigated the signal transduction pathway(s) responsible for the effects observed. Experimental approach: Intestinal epithelial cell 18, a non-tumour cell line with intestinal epithelial phenotype, was used. COX-2 was measured by Western blot and the involvement of the NF-kappa B pathway assessed by Western blot, pharmacological inhibition, luciferase reporter assays and nuclear translocation experiments. Key results: The effect of flavonoids on COX-2 expression depended on the experimental conditions tested [non-stimulated and lipopolysaccharide (LPS)-stimulated]. Flavonoids caused an increase in COX-2 expression and NF-kappa B-dependent gene transcription under basal conditions. Conversely, under LPS stimulation flavonoids increased, decreased or did not affect COX-2 levels depending on the specific type. Variable effects were observed on extracellular signal regulated kinase/p38/c-Jun N-terminal kinase phosphorylation and p50/65 nuclear translocation. Conclusion and implications: The effect of flavonoids on COX-2 expression depended on the balance of the interference with I kappa B-alpha phosphorylation and other signalling targets, and therefore depends on the experimental conditions and on the type of flavonoids. This is expected to result in different effects in inflammatory conditions. In general, flavonoids may limit epithelial COX-2 expression in inflammatory conditions while favouring it when inflammation is not present. C1 [Lopez-Posadas, R.; Mascaraque, C.; Zarzuelo, A.; Sanchez de Medina, F.] Univ Granada, Sch Pharm, Dept Pharmacol, CIBERehd, E-18071 Granada, Spain. [Suarez, M. D.; Martinez-Augustin, O.] Univ Granada, Sch Pharm, Dept Biochem & Mol Biol 2, CIBERehd, E-18071 Granada, Spain. [Ballester, I.] Massachusetts Gen Hosp, Gastrointestinal Unit GRJ716, Boston, MA 02114 USA. RP de Medina, FS (reprint author), Univ Granada, Sch Pharm, Dept Pharmacol, CIBERehd, Campus Cartuja S-N, E-18071 Granada, Spain. EM fsanchez@ugr.es RI Zarzuelo, Antonio/L-2840-2014; Lorente, M Dolores/N-1313-2014; Suarez Ortega, Maria Dolores/H-1240-2015; Martinez Augustin, Olga/K-6720-2014 OI Suarez Ortega, Maria Dolores/0000-0003-3197-2518; Martinez Augustin, Olga/0000-0001-8291-3468 FU Instituto de Salud Carlos III [PI051625, PI051651]; Ministry of Science and Innovation [SAF2008-01432, AGL2008-04332]; CIBERehd; Ministerio de Educacion y Ciencia, Spain; European Regional Development Fund [BFU2007-30688-E/BFI] FX This work was supported by grants from the Instituto de Salud Carlos III (PI051625 and PI051651) and the Ministry of Science and Innovation (SAF2008-01432 and AGL2008-04332). The CIBERehd is funded by the Instituto de Salud Carlos III. IB and RLP are funded by the Ministry of Science and Innovation. CM is funded by CIBERehd. The group is member of the Network for Cooperative Research on Membrane Transport Proteins (REIT), co-funded by the Ministerio de Educacion y Ciencia, Spain and the European Regional Development Fund (Grant BFU2007-30688-E/BFI). NR 39 TC 12 Z9 13 U1 2 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 AUG PY 2010 VL 160 IS 7 BP 1714 EP 1726 DI 10.1111/j.1476-5381.2010.00827.x PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 621WM UT WOS:000279616400015 PM 20649574 ER PT J AU Lorenz, KA Malin, JL AF Lorenz, Karl A. Malin, Jennifer L. TI How Might VA-Medicare Differences Inform the Delivery of End-of-Life Cancer Care? SO CANCER LA English DT Editorial Material ID UNITED-STATES; ASSOCIATIONS; ACCESS; HEALTH; COSTS C1 [Lorenz, Karl A.] Vet Adm Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. [Lorenz, Karl A.] Vet Adm Greater Los Angeles Healthcare Syst, Div Palliat Care, Los Angeles, CA USA. [Lorenz, Karl A.; Malin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Malin, Jennifer L.] Vet Adm Greater Los Angeles Healthcare Syst, Div Hematol Oncol, Los Angeles, CA USA. RP Lorenz, KA (reprint author), Vet Adm Greater Los Angeles, VA Palliat Care Qual Improvement Resource Ctr, Vet Integrated Palliat Program, 11301 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM karl.lorenz@va.gov NR 16 TC 2 Z9 2 U1 0 U2 0 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 AUG 1 PY 2010 VL 116 IS 15 BP 3533 EP 3536 DI 10.1002/cncr.25101 PG 4 WC Oncology SC Oncology GA 629TS UT WOS:000280223200004 PM 20564077 ER PT J AU Wadlow, RC Ryan, DP AF Wadlow, Raymond C. Ryan, David P. TI The Role of Targeted Agents in Preoperative Chemoradiation for Rectal Cancer SO CANCER LA English DT Review DE rectal cancer; chemoradiation; targeted therapy; biomarkers; angiogenesis ID METASTATIC COLORECTAL-CANCER; GROWTH-FACTOR-RECEPTOR; PHASE-II TRIAL; TYROSINE KINASE INHIBITOR; TOTAL MESORECTAL EXCISION; VENOUS INFUSION 5-FLUOROURACIL; PATHOLOGICAL COMPLETE RESPONSE; FLUOROURACIL PLUS LEUCOVORIN; EXTERNAL-BEAM RADIOTHERAPY; K-RAS MUTATION AB In the United States, randomized trials have established preoperative chemoradiation as the standard of care for patients with locally advanced rectal cancer. Pathologic complete response (pCR) rates occur in 10% to 16% of patients and have been shown to be correlated with both disease-free and overall survival. Therefore, recent efforts incorporating newer cytotoxic and molecularly targeted agents into chemoradiotherapy regimens have reported the pCR rate to be a surrogate marker of clinical outcomes. Substitution of oral fluoropyrimidines, including capecitabine, for infusional 5-fluorouracil reportedly generated pCR rates of up to 32% in phase 2 studies, but definitive evaluation awaits results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 trial. Similarly, regimens incorporating irinotecan generated pCR rates as high as 38%, but to the authors' knowledge have not been evaluated in randomized trials. In contrast, 2 large randomized trials reported that the addition of weekly oxaliplatin to fluoropyrimidine-based chemoradiation led to an increase in grade 3/4 toxicity but no difference in pCR rates. Early phase trials evaluating the anti-epidermal growth factor receptor (EGFF) antibody cetuximab in combination with chemoradiation reported modest pCR rates of 5% to 12%, and efforts have focused on identifying biomarkers of response including EGFR copy number, k-ras mutational status, and both serum and tumor-specific expression of EGFR ligands. Finally, incorporation of the anti-vascular endothelial growth factor antibody bevacizumab into chemoradiation appears to be safe and feasible, with initial studies reporting a beneficial effect on vascular normalization and correlations between circulating biomarkers of angiogenesis and pathologic response. Future efforts should include prospective studies of these agents in biomarker-defined subpopulations, as well as studies of novel agents that target angiogenesis, tumor-stromal interaction, and the cell signaling pathways implicated in colorectal cancer. Cancer 2010;116;3537-48. (C) 2070 American Cancer Society. C1 [Wadlow, Raymond C.; Ryan, David P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02114 USA. RP Ryan, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, 55 Fruit St,Yawkey 7, Boston, MA 02114 USA. EM dpryan@partners.org NR 102 TC 15 Z9 17 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 AUG 1 PY 2010 VL 116 IS 15 BP 3537 EP 3548 DI 10.1002/cncr.25155 PG 12 WC Oncology SC Oncology GA 629TS UT WOS:000280223200005 PM 20564106 ER PT J AU Keating, NL Landrum, MB Lamont, EB Earle, CC Bozeman, SR McNeil, BJ AF Keating, Nancy L. Landrum, Mary Beth Lamont, Elizabeth B. Earle, Craig C. Bozeman, Samuel R. McNeil, Barbara J. TI End-of-Life Care for Older Cancer Patients in the Veterans Health Administration Versus the Private Sector SO CANCER LA English DT Article DE end-of-life care; lung cancer; colorectal cancer; metastatic cancer ID MEDICARE BENEFICIARIES; MYOCARDIAL-INFARCTION; PROPENSITY SCORE; QUALITY; INDICATORS; HOSPICE; SYSTEM; PLACE; DEATH; AGGRESSIVENESS AB BACKGROUND: Treatment of older cancer patients at the end of life has become increasingly aggressive, despite the absence of evidence for better outcomes. We compared aggressiveness of end-of-life care of older metastatic cancer patients treated in the Veterans Health Administration (VHA) and those under fee-for-service Medicare arrangements. METHODS: Using propensity score methods, we matched 2913 male veterans who were diagnosed with stage IV lung or colorectal cancer in 2001-2002 and died before 2006 with 2913 similar men enrolled in fee-for-service Medicare living in Surveillance, Epidemiology, and End Result (SEER) areas. We assessed chemotherapy within 14 days of death, intensive care unit (ICU) admissions within 30 days of death, and >1 emergency room visit within 30 days of death. RESULTS: Among matched cohorts, men treated in the VHA were less likely than men in the private sector to receive chemotherapy within 14 days of death (4.6% vs 7.5%, P < .001), be admitted to an ICU within 30 days of death (12.5% vs 19.7%, P < .001), or have >1 emergency room visit within 30 days of death (13.1 vs 14.7, P = .09). CONCLUSIONS: Older men with metastatic lung or colorectal cancer treated in the VHA healthcare system received less aggressive end-of-life care than similar men in fee-for-service Medicare. This may result from the absence of financial incentives for more intensive care in the VHA or because this integrated delivery system is better structured to limit potentially overly aggressive care. Additional studies are needed to assess whether men undergoing less aggressive end-of-life care also experience better outcomes. Cancer 2010;116;3732-9. (C) 2010 American Cancer Society. C1 [Keating, Nancy L.; Landrum, Mary Beth; Lamont, Elizabeth B.; McNeil, Barbara J.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Div Adult Oncol, Boston, MA 02114 USA. [Earle, Craig C.] Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. [Bozeman, Samuel R.] ABT Associates Inc, Cambridge, MA 02138 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU Department of Veterans Affairs through the Office of Policy and Planning FX This work was funded by the Department of Veterans Affairs through the Office of Policy and Planning as part of a larger evaluation of oncology care. NR 37 TC 37 Z9 38 U1 0 U2 0 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 AUG 1 PY 2010 VL 116 IS 15 BP 3732 EP 3739 DI 10.1002/cncr.25077 PG 8 WC Oncology SC Oncology GA 629TS UT WOS:000280223200027 PM 20564065 ER PT J AU Michaud, DS Vrieling, A Jiao, L Mendelsohn, JB Steplowski, E Lynch, SM Wactawski-Wende, J Arslan, AA Bueno-de-Mesquita, HB Fuchs, CS Gross, M Helzlsouer, K Jacobs, EJ LaCroix, A Petersen, G Zheng, W Allen, N Ammundadottir, L Bergmann, MM Boffetta, P Buring, JE Canzian, F Chanock, SJ Clavel-Chapelon, F Clipp, S Freiberg, MS Gaziano, JM Giovannucci, EL Hankinson, S Hartge, P Hoover, RN Hubbell, FA Hunter, DJ Hutchinson, A Jacobs, K Kooperberg, C Kraft, P Manjer, J Navarro, C Peeters, PHM Shu, XO Stevens, V Thomas, G Tjonneland, A Tobias, GS Trichopoulos, D Tumino, R Vineis, P Virtamo, J Wallace, R Wolpin, BM Yu, K Zeleniuch-Jacquotte, A Stolzenberg-Solomon, RZ AF Michaud, Dominique S. Vrieling, Alina Jiao, Li Mendelsohn, Julie B. Steplowski, Emily Lynch, Shannon M. Wactawski-Wende, Jean Arslan, Alan A. Bueno-de-Mesquita, H. Bas Fuchs, Charles S. Gross, Myron Helzlsouer, Kathy Jacobs, Eric J. LaCroix, Andrea Petersen, Gloria Zheng, Wei Allen, Naomi Ammundadottir, Laufey Bergmann, Manuela M. Boffetta, Paolo Buring, Julie E. Canzian, Federico Chanock, Stephen J. Clavel-Chapelon, Francoise Clipp, Sandra Freiberg, Matthew S. Gaziano, J. Michael Giovannucci, Edward L. Hankinson, Susan Hartge, Patricia Hoover, Robert N. Hubbell, F. Allan Hunter, David J. Hutchinson, Amy Jacobs, Kevin Kooperberg, Charles Kraft, Peter Manjer, Jonas Navarro, Carmen Peeters, Petra H. M. Shu, Xiao-Ou Stevens, Victoria Thomas, Gilles Tjonneland, Anne Tobias, Geoffrey S. Trichopoulos, Dimitrios Tumino, Rosario Vineis, Paolo Virtamo, Jarmo Wallace, Robert Wolpin, Brian M. Yu, Kai Zeleniuch-Jacquotte, Anne Stolzenberg-Solomon, Rachael Z. TI Alcohol intake and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan) SO CANCER CAUSES & CONTROL LA English DT Article DE Alcohol; Pancreatic cancer; Pooled analysis ID BASE-LINE CHARACTERISTICS; GENOME-WIDE ASSOCIATION; LIFE-STYLE FACTORS; WOMENS HEALTH; UNITED-STATES; COFFEE CONSUMPTION; RISK; TOBACCO; DESIGN; SUSCEPTIBILITY AB The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer; however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed these associations using 1,530 pancreatic cancer cases and 1,530 controls from the Pancreatic Cancer Cohort Consortium (PanScan) nested case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for potential confounders. We observed no significant overall association between total alcohol (ethanol) intake and pancreatic cancer risk (OR = 1.38, 95% CI = 0.86-2.23, for 60 or more g/day vs. > 0 to < 5 g/day). A statistically significant increase in risk was observed among men consuming 45 or more grams of alcohol from liquor per day (OR = 2.23, 95% CI = 1.02-4.87, compared to 0 g/day of alcohol from liquor, P-trend = 0.12), but not among women (OR = 1.35, 95% CI = 0.63-2.87, for 30 or more g/day of alcohol from liquor, compared to none). No associations were noted for wine or beer intake. Overall, no significant increase in risk was observed, but a small effect among heavy drinkers cannot be ruled out. C1 [Michaud, Dominique S.; Peeters, Petra H. M.; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Michaud, Dominique S.; Giovannucci, Edward L.; Hankinson, Susan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Vrieling, Alina; Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Jiao, Li; Mendelsohn, Julie B.; Ammundadottir, Laufey; Chanock, Stephen J.; Hartge, Patricia; Hoover, Robert N.; Hutchinson, Amy; Jacobs, Kevin; Thomas, Gilles; Tobias, Geoffrey S.; Yu, Kai; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA. [Lynch, Shannon M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU Canc Inst, New York, NY USA. [Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Hankinson, Susan; Hunter, David J.; Wolpin, Brian M.] Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. [Helzlsouer, Kathy] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Jacobs, Eric J.; Stevens, Victoria] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [LaCroix, Andrea; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Petersen, Gloria] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Allen, Naomi] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Ammundadottir, Laufey; Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, US Dept HHS,NIH, Bethesda, MD 20892 USA. [Bergmann, Manuela M.] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany. [Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Clavel-Chapelon, Francoise] Inst Gustave Roussy, Villejuif, France. [Clavel-Chapelon, Francoise] INSERM, Villejuif, France. [Clipp, Sandra] George W Comstock Ctr Publ Hlth Res & Prevent, Johns Hopkins Bloomberg Sch Publ Hlth, Hagerstown, MD USA. [Freiberg, Matthew S.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hubbell, F. Allan] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. [Tumino, Rosario] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece. [Tumino, Rosario] Civile MP Arezzo Hosp, Canc Registry, Ragusa, Italy. [Tumino, Rosario] Civile MP Arezzo Hosp, Dept Histopathol, Ragusa, Italy. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wallace, Robert] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Wallace, Robert] Univ Iowa, Dept Internal Med, Coll Publ Hlth, Iowa City, IA 52242 USA. [Wallace, Robert] Univ Iowa, Coll Med, Dept Epidemiol, Iowa City, IA 52242 USA. [Wallace, Robert] Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. RP Michaud, DS (reprint author), Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. EM d.michaud@imperial.ac.uk RI Clavel-Chapelon, Francoise/G-6733-2014; Michaud, Dominique/I-5231-2014; Vrieling, Alina/A-2725-2016; Tobias, Geoffrey/M-4135-2016; OI Tobias, Geoffrey/0000-0002-2878-8253; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NCI NIH HHS [P01 CA087969, P01 CA087969-12, R01 CA082729, R01 CA124908, R37 CA070867] NR 41 TC 42 Z9 44 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2010 VL 21 IS 8 BP 1213 EP 1225 DI 10.1007/s10552-010-9548-z PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 627TI UT WOS:000280065400007 PM 20373013 ER PT J AU Barnett, CM Nielson, CM Shannon, J Chan, JM Shikany, JM Bauer, DC Hoffman, AR Barrett-Connor, E Orwoll, E Beer, TM AF Barnett, Christine M. Nielson, Carrie M. Shannon, Jackie Chan, June M. Shikany, James M. Bauer, Douglas C. Hoffman, Andrew R. Barrett-Connor, Elizabeth Orwoll, Eric Beer, Tomasz M. TI Serum 25-OH vitamin D levels and risk of developing prostate cancer in older men SO CANCER CAUSES & CONTROL LA English DT Article DE Vitamin D; Prostate cancer ID UNITED-STATES; 1,25-DIHYDROXYVITAMIN D-3; SUBSEQUENT DEVELOPMENT; ULTRAVIOLET-RADIATION; D METABOLITES; COLON-CANCER; D DEFICIENCY; IN-VIVO; 25-HYDROXYVITAMIN-D; MORTALITY AB Multiple studies have shown clear evidence of vitamin D's anti-tumor effects on prostate cancer cells in laboratory experiments, but the evidence has not been consistent in humans. We sought to examine the association between vitamin D and prostate cancer risk in a cohort of older men. We conducted a prospective case-cohort study nested within the multicenter Osteoporotic Fractures in Men (MrOS) study. Baseline serum 25-OH vitamin D was measured in a randomly selected sub-cohort of 1,433 men a parts per thousand yen65 years old without a history of prostate cancer and from all participants with an incident diagnosis of prostate cancer (n = 297). Cox proportional hazards models were used to evaluate the associations between quartiles of total 25-OH vitamin D and incident prostate cancer, as well as Gleason score. In comparison with the lowest quartile of 25-OH vitamin D, the hazard ratio for the highest quartile of 25-OH vitamin D was 1.22 (CI 0.50-1.72, p = 0.25), no trend across quartiles (p = 0.94) or association with Gleason score was observed. Adjustment for covariates did not alter the results. In this prospective cohort of older men, we found no association between serum 25-OH vitamin D levels and subsequent risk of prostate cancer. C1 [Barnett, Christine M.; Beer, Tomasz M.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Barnett, Christine M.; Beer, Tomasz M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Nielson, Carrie M.; Shannon, Jackie] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Shannon, Jackie] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. [Shannon, Jackie] Oregon Hlth & Sci Univ, CROET, Portland, OR 97239 USA. [Chan, June M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Chan, June M.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Shikany, James M.] Univ Alabama, Div Prevent Med, Birmingham, AL USA. [Hoffman, Andrew R.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, Dept Family & Prevent Med, Div Epidemiol, San Diego, CA 92103 USA. [Orwoll, Eric] Oregon Hlth & Sci Univ, Div Endocrinol, Bone & Mineral Unit, Portland, OR 97239 USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, CH-14R,3303 SW Bond Ave, Portland, OR 97239 USA. EM beert@ohsu.edu OI Orwoll, Eric/0000-0002-8520-7355 FU NIA NIH HHS [U01 AG042140] NR 47 TC 25 Z9 26 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2010 VL 21 IS 8 BP 1297 EP 1303 DI 10.1007/s10552-010-9557-y PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 627TI UT WOS:000280065400015 PM 20383574 ER PT J AU Mekary, RA Wu, KN Giovannucci, E Sampson, L Fuchs, C Spiegelman, D Willett, WC Smith-Warner, SA AF Mekary, Rania A. Wu, Kana Giovannucci, Edward Sampson, Laura Fuchs, Charles Spiegelman, Donna Willett, Walter C. Smith-Warner, Stephanie A. TI Total antioxidant capacity intake and colorectal cancer risk in the Health Professionals Follow-up Study SO CANCER CAUSES & CONTROL LA English DT Article DE Total antioxidant capacity (TAC); FRAP; Colorectal cancer; Nutrition ID FOOD-FREQUENCY QUESTIONNAIRE; PLANT FOODS; REPRODUCIBILITY; PREVENTION; VALIDITY; DISEASE AB To examine the association between total antioxidant capacity (TAC) intake and colorectal cancer incidence. TAC intake was assessed in 1986 and every 4 years thereafter in the Health Professionals Follow-up Study, a prospective cohort study of 47,339 men. Between 1986 and 2004, 952 colorectal cancer cases were diagnosed. Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). Comparing the highest versus lowest quintile, TAC intake from foods only (dietary TAC) was not associated with colorectal (multivariate-RR: 0.98; 95% CI: 0.78, 1.23) or colon (multivariate-RR: 1.20; 95% CI: 0.90, 1.61) cancer risk, but was inversely associated with rectal cancer risk (multivariate-RR: 0.58; 95% CI: 0.35, 0.96). For the same comparison, TAC intake from foods and supplements (total TAC) was not associated with colorectal (multivariate-RR: 0.91; 95% CI: 0.73, 1.14), colon (multivariate-RR: 1.01; 95% CI: 0.77, 1.33), or rectal (multivariate-RR: 0.85; 95% CI: 0.52, 1.38) cancer risk. Dietary and total TAC intakes were not associated with colorectal and colon cancer risk. Dietary, but not total, TAC intake was inversely associated with rectal cancer risk, suggesting antioxidants per se may not be associated with rectal cancer risk. C1 [Mekary, Rania A.; Wu, Kana; Giovannucci, Edward; Sampson, Laura; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Mekary, Rania A.; Giovannucci, Edward; Spiegelman, Donna; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward; Fuchs, Charles; Willett, Walter C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA USA. [Fuchs, Charles] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Mekary, RA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2,Rm 355A, Boston, MA 02115 USA. EM Rmekary@hsph.harvard.edu FU National Institutes for Health [CA098566, CA55075] FX This work was supported by CA098566 and CA55075 from the National Institutes for Health. NR 22 TC 19 Z9 19 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2010 VL 21 IS 8 BP 1315 EP 1321 DI 10.1007/s10552-010-9559-9 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 627TI UT WOS:000280065400017 PM 20390446 ER PT J AU Chiorean, EG Malireddy, S Younger, AE Jones, DR Waddell, MJ Sloop, MI Yu, MG Hall, SD Schneider, B Sweeney, CJ AF Chiorean, E. Gabriela Malireddy, Srikar Younger, Anne E. Jones, David R. Waddell, Mary-Jane Sloop, Melissa I. Yu, Menggang Hall, Stephen D. Schneider, Bryan Sweeney, Christopher J. TI A phase I dose escalation and pharmacokinetic study of vatalanib (PTK787/ZK 222584) in combination with paclitaxel in patients with advanced solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Paclitaxel; Phase I; PTK/ZK; VEGFR ID ENDOTHELIAL GROWTH-FACTOR; ADVANCED COLORECTAL-CANCER; RECEPTOR TYROSINE KINASES; METASTATIC BREAST-CANCER; HUMAN LIVER-MICROSOMES; CELL LUNG-CANCER; OVARIAN-CANCER; INHIBITOR; CARBOPLATIN; METABOLISM AB To define the maximum-tolerated dose (MTD) for weekly paclitaxel administered in combination with daily vatalanib (PTK787/ZK 222584, PTK/ZK) and assess for a drug-drug interaction. Patients were treated with escalating doses of weekly paclitaxel (75-85 mg/m(2)), and daily PTK/ZK (250-1,000 mg). During the first cycle only, paclitaxel was given on days 1 and 15, and PTK/ZK on days 3-28. Pharmacokinetic studies were conducted on cycle 1 days 1 and 15 for paclitaxel, and on cycle 1 day 15 for PTK/ZK. Therapy was given until disease progression. Twenty-seven patients were accrued to four dose levels. Two of five patients treated with paclitaxel 85 mg/m(2) and PTK/ZK 1,000 mg had Grade 3 transaminase elevation as dose-limiting toxicity. Paired PK analyses demonstrated a significant increase in paclitaxel clearance on day 15 (p = 0.006). Activity included one partial response and 11 patients with stable disease a parts per thousand yen4 months, including patients previously treated with paclitaxel. The MTD for weekly paclitaxel plus daily PTK/ZK is 75 mg/m(2) and 750 mg. PK analysis revealed a significant drug-drug interaction, with an increase in paclitaxel clearance. This combination was well tolerated with evidence of anti-cancer activity and provides guidance for phase 2 planning. C1 [Sweeney, Christopher J.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med, Boston, MA 02115 USA. [Yu, Menggang] Indiana Univ, Dept Biostat, Indianapolis, IN 46204 USA. [Chiorean, E. Gabriela; Malireddy, Srikar; Younger, Anne E.; Jones, David R.; Waddell, Mary-Jane; Sloop, Melissa I.; Hall, Stephen D.; Schneider, Bryan; Sweeney, Christopher J.] Indiana Univ, Dept Med, Simon Canc Ctr, Indianapolis, IN USA. RP Sweeney, CJ (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med, 44 Binney St,Rm 1230, Boston, MA 02115 USA. EM Christopher_Sweeney@dfci.harvard.edu FU Novartis Pharmaceuticals; Indiana University School of Medicine [M01RR00750] FX Supported by Novartis Pharmaceuticals; General Clinical Research Center at Indiana University School of Medicine M01RR00750. NR 27 TC 4 Z9 4 U1 0 U2 1 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 AUG PY 2010 VL 66 IS 3 BP 441 EP 448 DI 10.1007/s00280-009-1179-2 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 611PJ UT WOS:000278831600004 PM 20091169 ER PT J AU Grundmark, B Garmo, H Loda, M Busch, C Holmberg, L Zethelius, B AF Grundmark, Birgitta Garmo, Hans Loda, Massimo Busch, Christer Holmberg, Lars Zethelius, Bjorn TI The Metabolic Syndrome and the Risk of Prostate Cancer under Competing Risks of Death from Other Causes SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; MYOCARDIAL-INFARCTION; MEN; COHORT; SIZE; PREVENTION; COMPONENTS; PREDICTOR; SURVIVAL; REGISTER AB Background: Associations between metabolic syndrome (MetS) components and prostate cancer development have not been studied comprehensively; results have been divergent. Using the National Cholesterol Education Program Adult Treatment panel III (NCEP) and International Diabetes Federation (IDF) definitions of the MetS, we investigated such associations taking competing risks of death into consideration. Methods: In the prospective Uppsala Longitudinal Study of Adult Men of 2,322 Caucasian men with 34 years of follow-up baseline, MetS measurements at age 50 years were used. Cumulative incidence of prostate cancer and death with/without the MetS were calculated. Competing risk of dying was taken into account by calculating the conditional probability of prostate cancer with/without the MetS. Results: Two hundred and thirty-seven prostate cancers were identified. Prostate cancer probability by age 80 years with baseline MetS compared with without MetS was nonsignificantly higher [5.2 percent units (confidence interval (CI), -0.8% to 11.3%; NCEP); 2.7 percent units (CI, -2.7% to 8.0%; IDF)]; cumulative incidence proportions of death was significantly higher [19.3 percent units (CI, 13.4-25.3%; NCEP); 15.3 percent units (CI, 9.5-21.1%; IDF)]; and conditional probability of prostate cancer considering death from other causes was significantly higher [7.3 percent-units (CI, 0.2-14.5%); odds ratio of 1.64 (CI, 1.03-2.23; NCEP)] and nonsignificantly higher [5.0 percent-units (CI, -1.6% to 11.6%); odds ratio of 1.43 (CI, 0.89-1.90; IDF]. Conclusions: The MetS by the NCEP definition is associated with prostate cancer, taking the competing risk of early death from other causes into account. Impact: The results further highlight the public health effect of the increasing prevalence of MetS and the importance of considering competing risks when studying risk factors for cancer. Cancer Epidemiol Biomarkers Prev; 19(8); 2088-96. (C) 2010 AACR. C1 [Grundmark, Birgitta; Garmo, Hans; Holmberg, Lars] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden. [Busch, Christer] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. [Zethelius, Bjorn] Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden. [Grundmark, Birgitta; Garmo, Hans; Holmberg, Lars] Univ Uppsala Hosp, Reg Oncol Ctr Uppsala Orebro Reg, SE-75185 Uppsala, Sweden. [Grundmark, Birgitta; Zethelius, Bjorn] Med Prod Agcy, Uppsala, Sweden. [Garmo, Hans; Holmberg, Lars] Kings Coll London, Sch Med, Div Canc Studies, London WC2R 2LS, England. [Loda, Massimo] Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Grundmark, B (reprint author), Univ Uppsala Hosp, Reg Oncol Ctr, SE-75185 Uppsala, Sweden. EM birgitta.grundmark@surgsci.uu.se OI Garmo, Hans/0000-0001-7181-7083 FU Ernfors Family; Thuring; Thureus; Ake Wiberg Foundations; Swedish Diabetes Association; Swedish Medical Products Agency; Swedish Cancer Society; Cancer Research UK; Prostate Cancer Foundation; National Cancer Institute [RO1CA131945, P50 CA90381]; Dana-Farber Cancer Institute; Linda and Arthur Gelb Center for Translational Research FX Grants from the Ernfors Family(B. Zethelius), the Thuring (B. Zethelius), the Thureus (B. Zethelius) and the Ake Wiberg (B. Zethelius) Foundations, the Swedish Diabetes Association Research Fund (B. Zethelius), the Swedish Medical Products Agency (B. Grundmark and B. Zethelius), The Swedish Cancer Society (B. Grundmark and L. Holmberg), Cancer Research UK (H. Garmo and L. Holmberg), the Prostate Cancer Foundation (M. Loda), the National Cancer Institute grant RO1CA131945, P50 CA90381 (M. Loda), the Dana-Farber Cancer Institute-Novartis Drug Development Program (M. Loda), and the Linda and Arthur Gelb Center for Translational Research, a gift from Nuclea Biomarkers (M. Loda). NR 40 TC 33 Z9 33 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2010 VL 19 IS 8 BP 2088 EP 2096 DI 10.1158/1055-9965.EPI-10-0112 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 635RY UT WOS:000280675000023 PM 20647401 ER PT J AU Ghosh, SK Kim, P Zhang, XA Yun, SH Moore, A Lippard, SJ Medarova, Z AF Ghosh, Subrata K. Kim, Pilhan Zhang, Xiao-an Yun, Seok-Hyun Moore, Anna Lippard, Stephen J. Medarova, Zdravka TI A Novel Imaging Approach for Early Detection of Prostate Cancer Based on Endogenous Zinc Sensing SO CANCER RESEARCH LA English DT Article ID UPTAKE TRANSPORTER; TRANSGENIC MOUSE; TUMORS; RECEPTOR; ANTIGEN; CELLS; MODEL AB The early detection of prostate cancer is a life-saving event in patients harboring potentially aggressive disease. With the development of malignancy, there is a dramatic reduction in the zinc content of prostate tissue associated with the inability of cancer cells to accumulate the ion. In the current study, we used endogenous zinc as an imaging biomarker for prostate cancer detection and progression monitoring. We employed a novel fluorescent sensor for mobile zinc (ZPP1) to detect and monitor the development of prostate cancer in a transgenic mouse model of prostate adenocarcinoma, using in vivo optical imaging correlated with biological fluid-based methods. We showed that the progression of prostate cancer could be monitored in vivo judging by the decreasing zinc content in the prostates of tumor-bearing mice in an age-dependent manner. In a novel quantitative assay, we determined the concentration of mobile zinc in both prostate cell lysates and mouse prostate extracts through simple titration of the ZPP1 sensor. Our findings fulfill the promise of zinc-based prostate cancer diagnostics with the prospect for immediate clinical translation. Cancer Res; 70(15); 6119-27. (C) 2010 AACR. C1 [Ghosh, Subrata K.; Moore, Anna; Medarova, Zdravka] Harvard Univ, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Sch Med,Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Kim, Pilhan; Yun, Seok-Hyun] Harvard Univ, Wellman Ctr Photomed, Dept Dermatol, Sch Med,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Zhang, Xiao-an; Lippard, Stephen J.] MIT, Dept Chem, Cambridge, MA 02139 USA. RP Medarova, Z (reprint author), Harvard Univ, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Sch Med,Dept Radiol,Massachusetts Gen Hosp, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu; lippard@mit.edu; zmedarova@partners.org RI Kim, Pilhan/C-1836-2011; Zhang, Xiao-an/E-4458-2016 OI Kim, Pilhan/0000-0001-8388-1840; Zhang, Xiao-an/0000-0001-9417-4228 FU National Institute of General Medical Sciences [GM065519]; National Cancer Institute [R00CA129070]; National Institute of Diabetes and Digestive and Kidney Diseases [RC1DK086242]; Tosteson Postdoctoral Fellowship FX Work at the Massachusetts Institute of Technology was supported under grant GM065519 from the National Institute of General Medical Sciences. Work at the Martinos Center for Biomedical Imaging was supported in part under grant R00CA129070 from the National Cancer Institute. Work at the Wellman Center for Photomedicine was supported in part under grant RC1DK086242 from the National Institute of Diabetes and Digestive and Kidney Diseases and a Tosteson Postdoctoral Fellowship. NR 23 TC 47 Z9 47 U1 4 U2 22 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2010 VL 70 IS 15 BP 6119 EP 6127 DI 10.1158/0008-5472.CAN-10-1008 PG 9 WC Oncology SC Oncology GA 634CQ UT WOS:000280557500002 PM 20610630 ER PT J AU Monte, NM Webster, KA Neuberg, D Dressler, GR Mutter, GL AF Monte, Nicolas M. Webster, Kaitlyn A. Neuberg, Donna Dressler, Gregory R. Mutter, George L. TI Joint Loss of PAX2 and PTEN Expression in Endometrial Precancers and Cancer SO CANCER RESEARCH LA English DT Article ID INTRAEPITHELIAL-NEOPLASIA; TUMOR-SUPPRESSOR; WILMS-TUMOR; CARCINOMA; PROGRESSION; MARKER; BREAST; HYPERPLASIA; MUTATIONS; TAMOXIFEN AB Latent endometrial carcinoma precancers are normal-appearing endometrial glands with sporadic loss of tumor suppressor gene function such as PTEN. Progression to carcinoma is inefficient and requires additional genetic damage that creates a histologic precursor lesion called endometrial intraepithelial neoplasia (EIN). In this study, we examined loss of PAX2 expression, a gene required for embryonic uterine development, during endometrial carcinogenesis. Normal proliferative, EIN, and malignant (endometrial adenocarcinoma) endometrial tissues were immunostained for PTEN and PAX2. Proliferative samples with loss of protein in at least one gland were scored as latent precancers. EIN and cancer lesions were scored by the majority pattern. Overall prevalence and topography of joint PAX2-PTEN expression loss was examined. The prevalence of PAX2 protein loss in the sequence of normal to precancer to cancer was 36%, 71%, and 77%, respectively, and for PTEN, it was 49%, 44%, and 68%, respectively. The normal endometrial prevalence of PAX2- or PTEN-deficient latent precancers was unaffected by biopsy indication, but increased significantly with age. Coincident loss of PAX2 and PTEN expression in an individual normal endometrium was seen in 21% of patients, but usually involved different glands. Coincident loss was more common in precancers (31%) and carcinoma (55%), in which case, both markers were protein null in an overlapping clonal distribution. PAX2 and PTEN protein loss occurs independently and accumulates with increasing age in latent precancers of normal premenopausal endometrium. Loss of function of both genes in an overlapping distribution characterizes the clinical emergence of a premalignant lesion which is carried forward to carcinoma. Cancer Res; 70(15); 6225-32. (C) 2010 AACR. C1 [Mutter, George L.] Brigham & Womens Hosp, Div Womens & Perinatal Pathol, Dept Pathol, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Dressler, Gregory R.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Mutter, GL (reprint author), Brigham & Womens Hosp, Div Womens & Perinatal Pathol, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM gmutter@rics.bwh.harvard.edu FU NIH [RO1-CA100833] FX NIH grant RO1-CA100833 (G. Mutter). NR 30 TC 36 Z9 40 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2010 VL 70 IS 15 BP 6225 EP 6232 DI 10.1158/0008-5472.CAN-10-0149 PG 8 WC Oncology SC Oncology GA 634CQ UT WOS:000280557500012 PM 20631067 ER PT J AU Tyner, JW Fletcher, LB Wang, EQ Yang, WF Rutenberg-Schoenberg, ML Beadling, C Mori, M Heinrich, MC Deininger, MW Druker, BJ Loriaux, MM AF Tyner, Jeffrey W. Fletcher, Luke B. Wang, Ellen Q. Yang, Wayne F. Rutenberg-Schoenberg, Michael L. Beadling, Carol Mori, Motomi Heinrich, Michael C. Deininger, Michael W. Druker, Brian J. Loriaux, Marc M. TI MET Receptor Sequence Variants R970C and T992I Lack Transforming Capacity SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; ACTIVATING MUTATIONS; FUNCTIONAL-ANALYSIS; MYELOID-LEUKEMIA; FOLLOW-UP; C-MET; PROTOONCOGENE; EXPRESSION; GEFITINIB; CARCINOMA AB High-throughput sequencing promises to accelerate the discovery of sequence variants, but distinguishing oncogenic mutations from irrelevant "passenger" mutations remains a major challenge. Here we present an analysis of two sequence variants of the MET receptor (hepatocyte growth factor receptor) R970C and T992I (also designated R988C and T1010I). Previous reports indicated that these sequence variants are transforming and contribute to oncogenesis. We screened patients with chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), colorectal cancer, endometrial cancer, thyroid cancer, or melanoma, as well as individuals without cancer, and found these variants at low frequencies in most cohorts, including normal individuals. No evidence of increased phosphorylation or transformative capacity by either sequence variant was found. Because small-molecule inhibitors for MET are currently in development, it will be important to distinguish between oncogenic sequence variants and rare single-nucleotide polymorphisms to avoid the use of unnecessary, and potentially toxic, cancer therapy agents. Cancer Res; 70(15); 6233-7. (C) 2010 AACR. C1 [Tyner, Jeffrey W.; Fletcher, Luke B.; Wang, Ellen Q.; Yang, Wayne F.; Rutenberg-Schoenberg, Michael L.; Beadling, Carol; Mori, Motomi; Heinrich, Michael C.; Deininger, Michael W.; Druker, Brian J.; Loriaux, Marc M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Tyner, Jeffrey W.; Fletcher, Luke B.; Wang, Ellen Q.; Yang, Wayne F.; Rutenberg-Schoenberg, Michael L.; Deininger, Michael W.; Druker, Brian J.; Loriaux, Marc M.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. [Beadling, Carol; Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. [Mori, Motomi] Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Druker, Brian J.] Howard Hughes Med Inst, Portland, OR USA. [Loriaux, Marc M.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. RP Tyner, JW (reprint author), Oregon Hlth & Sci Univ, Knight Canc Inst, 3181 SW Sam Jackson Pk Rd,Mailcode L592, Portland, OR 97239 USA. EM tynerj@ohsu.edu OI Tyner, Jeffrey/0000-0002-2133-0960 FU Leukemia and Lymphoma Society; TJ Martell Foundation; Doris Duke Charitable Foundation; William Lawrence and Blanche Hughes Fund; National Center for Research Resources (NRCC); VA Merit Review Grant; OHSU cancer center [5 p30 CA069533]; Knight Cancer Institute [5P50CA069533]; Oregon Clinical & Translational Research Institute [UL1 RR024140] FX The Leukemia and Lymphoma Society, the TJ Martell Foundation, and the Doris Duke Charitable Foundation. J.W. Tyner is supported by grants from the William Lawrence and Blanche Hughes Fund, and the Oregon Clinical and Translational Research Institute (OCTRI) grant number UL1 RR024140 from the National Center for Research Resources (NRCC), a component of the NIH, and NIH Roadmap for Medical Research. M. C. Heinrich is supported in part by a VA Merit Review Grant. B.J. Druker is an investigator of the Howard Hughes Medical Institute and principal investigator of the OHSU cancer center support grant 5 p30 CA069533. M. M. Loriaux is supported by the Leukemia and Lymphoma Society and the TJ Martell Foundation. Biostatistics support (M. Mori) is in part provided by the Biostatistics Shared Resource of the Knight Cancer Institute (5P50CA069533) and the Biostatistics & Design Program of the Oregon Clinical & Translational Research Institute (UL1 RR024140). NR 22 TC 37 Z9 37 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2010 VL 70 IS 15 BP 6233 EP 6237 DI 10.1158/0008-5472.CAN-10-0429 PG 5 WC Oncology SC Oncology GA 634CQ UT WOS:000280557500013 PM 20670955 ER PT J AU Sasajima, J Mizukami, Y Sugiyama, Y Nakamura, K Kawamoto, T Koizumi, K Fujii, R Motomura, W Sato, K Suzuki, Y Tanno, S Fujiya, M Sasaki, K Shimizu, N Karasaki, H Kono, T Kawabe, J Ii, M Yoshiara, H Kamiyama, N Ashida, T Bardeesy, N Chung, DC Kohgo, Y AF Sasajima, Junpei Mizukami, Yusuke Sugiyama, Yoshiaki Nakamura, Kazumasa Kawamoto, Toru Koizumi, Kazuya Fujii, Rie Motomura, Wataru Sato, Kazuya Suzuki, Yasuaki Tanno, Satoshi Fujiya, Mikihiro Sasaki, Katsunori Shimizu, Norihiko Karasaki, Hidenori Kono, Toru Kawabe, Jun-ichi Ii, Masaaki Yoshiara, Hiroki Kamiyama, Naohisa Ashida, Toshifumi Bardeesy, Nabeel Chung, Daniel C. Kohgo, Yutaka TI Transplanting Normal Vascular Proangiogenic Cells to Tumor-Bearing Mice Triggers Vascular Remodeling and Reduces Hypoxia in Tumors SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL PROGENITOR CELLS; PANCREATIC-CANCER CELLS; STEM-CELLS; ADULT NEOVASCULARIZATION; HEDGEHOG PROMOTES; ANGIOGENESIS; GROWTH; GEMCITABINE; METASTASIS; EXPRESSION AB Blood vessels deliver oxygen and nutrients to tissues, and vascular networks are spatially organized to meet the metabolic needs for maintaining homeostasis. In contrast, the vasculature of tumors is immature and leaky, resulting in insufficient delivery of nutrients and oxygen. Vasculogenic processes occur normally in adult tissues to repair "injured" blood vessels, leading us to hypothesize that bone marrow mononuclear cells (BMMNC) may be able to restore appropriate vessel function in the tumor vasculature. Culturing BMMNCs in endothelial growth medium resulted in the early outgrowth of spindle-shaped attached cells expressing CD11b/Flt1/Tie2/c-Kit/CXCR4 with proangiogenic activity. Intravenous administration of these cultured vascular proangiogenic cells (VPC) into nude mice bearing pancreatic cancer xenografts and Pdx1-Cre; LSL-Kras(G12D);p53(lox/+) genetically engineered mice that develop pancreatic ductal adenocarcinoma significantly reduced areas of hypoxia without enhancing tumor growth. The resulting vasculature structurally mimicked normal vessels with intensive pericyte coverage. Increases in vascularized areas within VPC-injected xenografts were visualized with an ultrasound diagnostic system during injection of a microbubble-based contrast agent (Sonazoid), indicating a functional "normalization" of the tumor vasculature. In addition, gene expression profiles in the VPC-transplanted xenografts revealed a marked reduction in major factors involved in drug resistance and "stemness" of cancer cells. Together, our findings identify a novel alternate approach to regulate abnormal tumor vessels, offering the potential to improve the delivery and efficacy of anticancer drugs to hypoxic tumors. Cancer Res; 70(15); 6283-92. (C) 2010 AACR. C1 [Sasajima, Junpei; Mizukami, Yusuke; Sugiyama, Yoshiaki; Nakamura, Kazumasa; Kawamoto, Toru; Koizumi, Kazuya; Fujii, Rie; Motomura, Wataru; Sato, Kazuya; Suzuki, Yasuaki; Tanno, Satoshi; Fujiya, Mikihiro; Sasaki, Katsunori; Kohgo, Yutaka] Asahikawa Med Coll, Div Gastroenterol & Hematol Oncol, Dept Med, Asahikawa, Hokkaido 0788510, Japan. [Shimizu, Norihiko] Asahikawa Med Coll, Dept Anim Facil, Asahikawa, Hokkaido 0788510, Japan. [Karasaki, Hidenori; Kono, Toru] Asahikawa Med Coll, Div Gastroenterol & Gen Surg, Dept Surg, Asahikawa, Hokkaido 0788510, Japan. [Kawabe, Jun-ichi] Asahikawa Med Coll, Dept Cardiovasc Regenerat & Innovat, Asahikawa, Hokkaido 0788510, Japan. [Ii, Masaaki] Osaka Med Coll, Dept Pharmacol, Osaka, Japan. [Yoshiara, Hiroki; Kamiyama, Naohisa] Toshiba Med Syst Corp, Otawara, Tochigi, Japan. [Ashida, Toshifumi] Sapporo Higashi Tokusyukai Hosp, Ctr IBD, Sapporo, Hokkaido, Japan. [Bardeesy, Nabeel; Chung, Daniel C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bardeesy, Nabeel; Chung, Daniel C.] Harvard Univ, Sch Med, Boston, MA USA. RP Mizukami, Y (reprint author), Asahikawa Med Coll, Div Gastroenterol & Hematol Oncol, Dept Med, 2-1 Midorigaoka Higashi, Asahikawa, Hokkaido 0788510, Japan. EM mizu@asahikawa-med.ac.jp FU New Energy and Industrial Technology Development Organization of Japan [07A05010a] FX New Energy and Industrial Technology Development Organization of Japan grant 07A05010a (Y. Mizukami). NR 51 TC 16 Z9 16 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2010 VL 70 IS 15 BP 6283 EP 6292 DI 10.1158/0008-5472.CAN-10-0412 PG 10 WC Oncology SC Oncology GA 634CQ UT WOS:000280557500019 PM 20631070 ER PT J AU d'Othee, BJ Walker, TG Kalva, SP Ganguli, S Davison, B AF d'Othee, Bertrand Janne Walker, T. Gregory Kalva, Sanjeeva P. Ganguli, Suvranu Davison, Brian TI Endovenous Laser Ablation of the Small Saphenous Vein Sparing the Saphenopopliteal Junction SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Varicose vein; Endovenous ablation; Saphenous veins; Laser; Endovenous thermal ablation; Small saphenous vein ID RADIOFREQUENCY OBLITERATION; ARTERIOVENOUS-FISTULA; VENOUS INSUFFICIENCY; VARICOSE-VEINS; REFLUX; EXPERIENCE AB To assess outcomes after endovenous laser ablation (EVLA) of the small saphenous vein (SSV). Retrospective review was performed of all consecutive EVLA procedures performed over a 39-month period at three neighboring vein practices for symptomatic, duplex ultrasound-proven incompetence of the SSV. EVLA was performed under ultrasound guidance with an 810- or 980-nm diode laser in continuous mode using the pullback method while sparing the deep, most cephalad segment of the SSV near the saphenopopliteal junction. Follow-up after EVLA included patient symptoms, physical examination, and duplex ultrasound. Pretreatment variables were similar across all three practices. EVLA was performed to treat 67 incompetent SSVs in 63 patients (86% women; mean age and 95% confidence interval, 50 +/- A 3 years; range, 20-82 years). Average energy delivered was 92 J/cm. Immediate technical success and occlusion of the treated vein at 1-2 weeks was 100%. Imaging follow-up length was 243 +/- A 65 days (range, 3-893 days). Clinical follow-up (243 +/- A 66 days) showed symptomatic improvement in 66 (99%) of 67 patients; one patient had recanalization with recurrent reflux by ultrasound (2%). Complications included one case of paresthesias lasting beyond 1 month of follow-up (2%) and three cases of superficial phlebitis (4%), but no deep vein thrombosis, skin burns, or other complications. Although ablation involved only the superficial portion of the SSV and spared its deep segment in the popliteal fossa, SSV occlusion typically extended up to the saphenopopliteal junction or to a gastrocnemial collateral, without popliteal vein involvement. EVLA of the SSV is safe and effective when the saphenopopliteal junction and popliteal fossa are avoided. This approach may help reduce the risk of paresthesias or other complications while maintaining low recanalization rates. C1 [d'Othee, Bertrand Janne] Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Div Vasc & Intervent Radiol, Baltimore, MD 21201 USA. [d'Othee, Bertrand Janne; Walker, T. Gregory; Kalva, Sanjeeva P.; Ganguli, Suvranu; Davison, Brian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Imaging & Intervent,Dept Imaging, Boston, MA 02114 USA. [d'Othee, Bertrand Janne; Ganguli, Suvranu] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Davison, Brian] Lincoln Med Ctr, TVV, Framingham, MA 01702 USA. RP d'Othee, BJ (reprint author), Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Div Vasc & Intervent Radiol, 22 S Greene St, Baltimore, MD 21201 USA. EM bjannedothee@umm.edu NR 16 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 EI 1432-086X J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD AUG PY 2010 VL 33 IS 4 BP 766 EP 771 DI 10.1007/s00270-010-9806-1 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 629UQ UT WOS:000280225800017 ER PT J AU Robbins, CS Swirski, FK AF Robbins, Clinton S. Swirski, Filip K. TI The multiple roles of monocyte subsets in steady state and inflammation SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Monocyte subsets; Inflammation; Hematopoietic system; Macrophage; Dendritic cell ID HUMAN PERIPHERAL-BLOOD; CD8(+) T-CELLS; COUNTERFLOW CENTRIFUGATION ELUTRIATION; ATHEROSCLEROTIC LESION FORMATION; DENDRITIC CELLS; LYMPHOID ORGANS; BONE-MARROW; IN-VIVO; BACTERIAL-INFECTION; MYD88-DEPENDENT ACTIVATION AB Monocytes participate importantly in immunity. Produced in the bone marrow and released into the blood, they circulate in blood or reside in a spleen reservoir before entering tissue and giving rise to macrophages or dendritic cells. Monocytes are more than transitional cells that adapt to a particular tissue environment indiscriminately. Accumulating evidence now indicates that monocytes are heterogeneous in several species and are themselves predetermined for particular function in the steady state and inflammation. Future therapeutics may harness this heterogeneity to target harmful functions while sparing those that are beneficial. Here, we review recent advances on the ontogeny and function of monocytes and their subsets in humans and mice. C1 [Robbins, Clinton S.; Swirski, Filip K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Swirski, FK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM fswirski@mgh.harvard.edu FU NIH [1R01HL095612]; AHA FX This work was funded by NIH grant 1R01HL095612 (to FKS) and an AHA postdoctoral fellowship (to CSR). NR 109 TC 64 Z9 68 U1 0 U2 11 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD AUG PY 2010 VL 67 IS 16 BP 2685 EP 2693 DI 10.1007/s00018-010-0375-x PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 634FF UT WOS:000280564600002 PM 20437077 ER PT J AU Mishra, BB Moura-Alves, P Sonawane, A Hacohen, N Griffiths, G Moita, LF Anes, E AF Mishra, Bibhuti B. Moura-Alves, Pedro Sonawane, Avinash Hacohen, Nir Griffiths, Gareth Moita, Luis F. Anes, Elsa TI Mycobacterium tuberculosis protein ESAT-6 is a potent activator of the NLRP3/ASC inflammasome SO CELLULAR MICROBIOLOGY LA English DT Article ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; CASPASE-1 ACTIVATION; MURINE MACROPHAGES; NALP3 INFLAMMASOME; MURAMYL DIPEPTIDE; INDUCED APOPTOSIS; INFECTION; SECRETION; RECOGNITION; RECEPTORS AB P>Interleukin-1 beta (IL-1 beta) represents one of the most important mediators of inflammation and host responses to infection. Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, induces IL-1 beta secretion at the site of infection, but the underlying mechanism(s) are poorly understood. In this work we show that Mtb infection of macrophages stimulates caspase-1 activity and promotes the secretion of IL-1 beta. This stimulation requires live intracellular bacteria expressing a functional ESX-1 secretion system. ESAT-6, an ESX-1 substrate implicated in membrane damage, is both necessary and sufficient for caspase-1 activation and IL-1 beta secretion. ESAT-6 promotes the access of other immunostimulatory agents such as AG85 into the macrophage cytosol, indicating that this protein may contribute to caspase-1 activation largely by perturbing host cell membranes. Using a high-throughput shRNA-based screen we found that numerous NOD-like receptors (NLRs) and CARD domain-containing proteins (CARDs) were important for IL-1 beta secretion upon Mtb infection. Most importantly, NLRP3, ASC and caspase-1 form an infection-inducible inflammasome complex that is essential for IL-1 beta secretion. In summary, we show that recognition of Mtb infection by the NLRP3 inflammasome requires the activity of the bacterial virulence factor ESAT-6, and the subsequent IL-1 beta response is regulated by a number of NLR/CARD proteins. C1 [Moura-Alves, Pedro; Moita, Luis F.] Univ Lisbon, Fac Med, Inst Mol Med, Cell Biol Immune Syst Unit, P-1649028 Lisbon, Portugal. [Mishra, Bibhuti B.; Anes, Elsa] Univ Lisbon, Fac Farm, Ctr Patogenese Mol, Unidade Retrovirus & Infeccoes Associadas, P-1649028 Lisbon, Portugal. [Mishra, Bibhuti B.; Anes, Elsa] Univ Lisbon, Fac Farm, Inst Mol Med, P-1649028 Lisbon, Portugal. [Moura-Alves, Pedro] Univ Porto, Abel Salazar Inst Biomed Sci, Grad Program Basic & Appl Biol, P-4099003 Oporto, Portugal. [Sonawane, Avinash; Griffiths, Gareth] Univ Oslo, Dept Mol Biosci, N-0316 Oslo, Norway. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. [Hacohen, Nir] Broad Inst Harvard, Cambridge, MA 02142 USA. [Hacohen, Nir] MIT, Cambridge, MA 02142 USA. RP Moita, LF (reprint author), Univ Lisbon, Fac Med, Inst Mol Med, Cell Biol Immune Syst Unit, P-1649028 Lisbon, Portugal. EM lmoita@fm.ul.pt; eanes@ff.ul.pt RI Moita, Luis/L-1296-2013; iMed.ULisboa, iMed.ULisboa/C-6292-2014; Anes, Elsa/K-3124-2013; iMed.ULisboa, HPI /B-4239-2014 OI Moita, Luis/0000-0003-0707-315X; Anes, Elsa/0000-0001-5934-0198; iMed.ULisboa, HPI /0000-0001-5934-0198 FU National Foundation for Science-FCT [PPCDT/BIA-BCM/55327/2004, PIC/IC/82859/2007, SFRH/BD/28173/2006, SFRH/BD/15238/2004]; Human Frontier Science Program; FLAD; FCT [PTDC/SAU-MII/69280/2006, PTDC/SAU-MII/78333/2006] FX We thank Dr Christopher Sassetti for his critical review of the manuscript and helpful suggestions. We are thankful to Drs Fernando Maltez, Amelia Pimpao and Lurdes Fernandes for providing us the blood samples from TB patients. We thank Dr Takahashi Miyashita for providing the p11-GFP and p45-GFP plasmids. We are also grateful for the reagents provided by the Colorado State University, USA and by the Centralised Facility for AIDS Reagents (NISB). We thank Professor David R Sherman of the Seattle Biomedical Research Institute, USA for providing us the Mtb mutant strains. This work was supported by grants from the National Foundation for Science-FCT project PPCDT/BIA-BCM/55327/2004, PIC/IC/82859/2007 to E.A., SFRH/BD/28173/2006 fellowship to B.B.M. and SFRH/BD/15238/2004 fellowship to P.M.-A. L.F.M. is a Young Investigator from the Human Frontier Science Program and receives support from FLAD and FCT (PTDC/SAU-MII/69280/2006 and PTDC/SAU-MII/78333/2006). NR 64 TC 130 Z9 133 U1 2 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD AUG PY 2010 VL 12 IS 8 BP 1046 EP 1063 DI 10.1111/j.1462-5822.2010.01450.x PG 18 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 623ER UT WOS:000279721400004 PM 20148899 ER PT J AU Stevens, WD Buckner, RL Schacter, DL AF Stevens, W. Dale Buckner, Randy L. Schacter, Daniel L. TI Correlated Low-Frequency BOLD Fluctuations in the Resting Human Brain Are Modulated by Recent Experience in Category-Preferential Visual Regions SO CEREBRAL CORTEX LA English DT Article DE fMRI; functional connectivity; intrinsic activity; network; resting-state ID STATE FUNCTIONAL CONNECTIVITY; DEFAULT-MODE NETWORK; FUSIFORM FACE AREA; EVENT-RELATED FMRI; STRUCTURAL CONNECTIVITY; ALZHEIMERS-DISEASE; COMPONENT ANALYSIS; NEURAL ACTIVITY; CORTEX; MEMORY AB The resting brain is associated with significant intrinsic activity fluctuations, such as the correlated low-frequency (IF) blood oxygen level-dependent (BOLD) fluctuations measured by functional magnetic resonance imaging. Despite a recent expansion of studies investigating resting-state LF-BOLD correlations, their nature and function are poorly understood. A major constraint on IF-BOLD correlations appears to be stable properties of anatomic connectivity. There is also evidence that coupling can be modulated by recent or ongoing task performance, suggesting that certain components of correlated dynamics are malleable on short timescales. Here, we compared activity during extended periods of rest following performance of 2 distinct cognitive tasks using different categories of visual stimuli faces and complex scenes. Prolonged exposure to these distinct categories of visual information caused frontal networks to couple differentially with posterior category-preferential visual regions during subsequent periods of rest. In addition, we report preliminary evidence suggesting that conditions exist in which the degree of modulation of LF-BOLD correlations predicts subsequent memory. The finding that resting-state IF-BOLD correlations are modulated by recent experience in functionally specific brain regions engaged during prior task performance clarifies their role as a dynamic phenomenon which may be involved in mnemonic processes. C1 [Stevens, W. Dale; Buckner, Randy L.; Schacter, Daniel L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Stevens, W. Dale; Buckner, Randy L.; Schacter, Daniel L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Stevens, WD (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM dstevens@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061 FU National Institutes of Health [MH060941, AG021910]; Howard Hughes Medical Institute FX National Institutes of Health (MH060941 to D.L.S.); Howard Hughes Medical Institute and a National Institutes of Health (AG021910 to R.L.B.). NR 68 TC 90 Z9 91 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD AUG PY 2010 VL 20 IS 8 BP 1997 EP 2006 DI 10.1093/cercor/bhp270 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 634QD UT WOS:000280597100022 PM 20026486 ER PT J AU O'Donnell, CR Bankier, AA Stiebellehner, L Reilly, JJ Brown, R Loring, SH AF O'Donnell, Carl R. Bankier, Alexander A. Stiebellehner, Leopold Reilly, John J. Brown, Robert Loring, Stephen H. TI Comparison Among Different Methods on Measurement of Total Lung Capacity in COPD Response SO CHEST LA English DT Letter ID VOLUMES C1 [O'Donnell, Carl R.] Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Dept Pulm & Crit Care Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bankier, Alexander A.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA. [Loring, Stephen H.] Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA USA. [Stiebellehner, Leopold] Med Univ Vienna, Dept Pulmonol, Vienna, Austria. [Reilly, John J.] Univ Pittsburgh, Div Pulm & Crit Care Med, Pittsburgh, PA USA. [Brown, Robert] Massachusetts Gen Hosp, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. RP O'Donnell, CR (reprint author), Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Dept Pulm & Crit Care Med, Beth Israel Deaconess Med Ctr, E Dana 717,330 Brookline Ave, Boston, MA 02215 USA. RI Reilly, John/H-8755-2012 NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2010 VL 138 IS 2 BP 459 EP 460 DI 10.1378/chest.10-1093 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 636NI UT WOS:000280743600038 ER PT J AU Hawkins, AO Danielson, CK de Arellano, MA Hanson, RF Ruggiero, KJ Smith, DW Saunders, BE Kilpatrick, DG AF Hawkins, Alesia Oscea Danielson, Carla Kmett de Arellano, Michael A. Hanson, Rochelle F. Ruggiero, Kenneth J. Smith, Daniel W. Saunders, Benjamin E. Kilpatrick, Dean G. TI Ethnic/Racial Differences in the Prevalence of Injurious Spanking and Other Child Physical Abuse in a National Survey of Adolescents SO CHILD MALTREATMENT LA English DT Article DE adolescent victims; ethnic minority populations; physical abuse ID VIOLENCE; VICTIMIZATION; MALTREATMENT; PUNISHMENT; YOUTH AB Limited research has examined whether similar patterns in injurious spanking and other forms of child physical abuse (CPA) exist across specific ethnic/racial groups. The authors examined and compared differences in the lifetime prevalence of injurious spanking and CPA in two national samples of adolescents across ethnic/racial groups and over time. Participants were 4,023 youth (12-17 years) and 3,614 youth (12-17 years) who participated in the 1995 National Survey of Adolescents (NSA) and 2005 National Survey of Adolescents-Replication (NSA-R), respectively. Adolescents, who were identified through random digit dial procedures, completed a telephone interview assessment. Results indicated significant ethnic/racial variation across groups in reports of injurious spanking in the NSA and the NSA-R samples; however, significant differences were not observed within groups between the two samples over time. Ethnic/racial differences also were found between groups in reports of CPA in the NSA-R sample. Limitations and future directions of this research are discussed. C1 [Hawkins, Alesia Oscea] Univ Illinois, Coll Med Rockford, Dept Family & Community Med, Rockford, IL 61107 USA. [de Arellano, Michael A.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, COPE, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Hawkins, AO (reprint author), Univ Illinois, Coll Med Rockford, Dept Family & Community Med, 1601 Parkview Ave, Rockford, IL 61107 USA. EM alesiah@uic.edu FU NICHD NIH HHS [R01 HD046830]; NIDA NIH HHS [K23DA018686] NR 21 TC 18 Z9 18 U1 1 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5595 J9 CHILD MALTREATMENT JI Child Maltreatment PD AUG PY 2010 VL 15 IS 3 BP 242 EP 249 DI 10.1177/1077559510367938 PG 8 WC Family Studies; Social Work SC Family Studies; Social Work GA 628PJ UT WOS:000280132400005 PM 20498129 ER PT J AU Thanassoulis, G Massaro, JM O'Donnell, CJ Hoffmann, U Levy, D Ellinor, PT Wang, TJ Schnabel, RB Vasan, RS Fox, CS Benjamin, EJ AF Thanassoulis, George Massaro, Joseph M. O'Donnell, Christopher J. Hoffmann, Udo Levy, Daniel Ellinor, Patrick T. Wang, Thomas J. Schnabel, Renate B. Vasan, Ramachandran S. Fox, Caroline S. Benjamin, Emelia J. TI Pericardial Fat Is Associated With Prevalent Atrial Fibrillation The Framingham Heart Study SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; pericardial adipose tissue; obesity; epidemiology; risk factor ID EPICARDIAL ADIPOSE-TISSUE; P-WAVE DISPERSION; CORONARY-ARTERY-DISEASE; VISCERAL ABDOMINAL FAT; LIPOMATOUS HYPERTROPHY; OBESE SUBJECTS; INTERATRIAL SEPTUM; WEIGHT-LOSS; CLINICAL-SIGNIFICANCE; MORPHOLOGIC FEATURES AB Background-Obesity represents an important risk factor for atrial fibrillation (AF). We tested the hypothesis that pericardial fat, a unique fat deposit in close anatomic proximity to cardiac structures and autonomic fibers, is associated with prevalent AF. Methods and Results-Participants from the Framingham Heart Study underwent multidetector computed tomography from 2002 to 2005. We estimated the association between quantitative pericardial, intrathoracic and visceral adipose tissue volumes (per standard deviation of volume) with prevalent AF adjusting for established AF risk factors (age, sex, systolic blood pressure, blood pressure treatment, PR interval, and clinically significant valvular disease). Of the 3217 eligible participants (mean age, 50.6 +/- 10.1 years; 48% women), 54 had a confirmed diagnosis of AF. Pericardial fat but not intrathoracic or visceral abdominal fat was associated with prevalent AF in multivariable-adjusted models (odds ratio per standard deviation of pericardial fat volume, 1.28; 95% confidence intervals, 1.03 to 1.58). Further adjustments for body mass index, heart failure, myocardial infarction, and intrathoracic fat volume did not materially change the association between pericardial fat and AF. Conclusions-Pericardial fat was associated with prevalent AF even after adjustment for AF risk factors, including body mass index. If this association is replicated, further investigations into the mechanisms linking pericardial fat to AF are merited. (Circ Arrhythm Electrophysiol. 2010;3:345-350.) C1 [Thanassoulis, George; O'Donnell, Christopher J.; Levy, Daniel; Schnabel, Renate B.; Vasan, Ramachandran S.; Fox, Caroline S.; Benjamin, Emelia J.] Boston Univ, Framingham, MA 01702 USA. NHLBI, NIH, Framingham, MA 01702 USA. [Thanassoulis, George; Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Massaro, Joseph M.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [O'Donnell, Christopher J.; Hoffmann, Udo; Ellinor, Patrick T.; Wang, Thomas J.; Fox, Caroline S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hoffmann, Udo] MGH PET MR CT Program, Boston, MA USA. [O'Donnell, Christopher J.; Levy, Daniel; Fox, Caroline S.] NIH, Div Intramural Res, Bethesda, MD 20892 USA. RP Benjamin, EJ (reprint author), Boston Univ, 73 Mt Wayte Ave,2, Framingham, MA 01702 USA. EM emelia@bu.edu RI Schnabel, Renate/F-6527-2014; OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Framingham Heart Study, Boston University; National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC 25195]; Canadian Institute of Health Research; Fonds de Recherche en Sante Quebec; [1R01HL092577]; [RO1 HL076784]; [1RC1HL101056]; [R01 AG028321]; [R01-DK-080739] FX This study was supported by the Framingham Heart Study, Boston University and the National Institutes of Health/National Heart, Lung, and Blood Institute, grant N01-HC 25195. Dr Thanassoulis is supported by a Research Fellowship from the Canadian Institute of Health Research and the Fonds de Recherche en Sante Quebec. Dr Benjamin was supported in part by grants 1R01HL092577, RO1 HL076784, 1RC1HL101056, and R01 AG028321. Dr Vasan was supported in part by grant R01-DK-080739. NR 46 TC 112 Z9 114 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD AUG PY 2010 VL 3 IS 4 BP 345 EP 350 DI 10.1161/CIRCEP.109.912055 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 639WI UT WOS:000281006700008 PM 20558845 ER PT J AU Mills, RW Milan, DJ AF Mills, Robert W. Milan, David J. TI Trpm4-Linked Isolated Cardiac Conduction Defects Bad Trafficking Causes Electrical Gridlock SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Editorial Material DE Editorials; conduction; genetics ID PR INTERVAL; HEART; SUMOYLATION; ARRHYTHMIA; DISEASES; TRPM4 C1 [Milan, David J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Mills, Robert W.; Milan, David J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Milan, DJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM DMilan@Partners.org NR 18 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD AUG PY 2010 VL 3 IS 4 BP 311 EP 313 DI 10.1161/CIRCGENETICS.110.957670 PG 3 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 639WH UT WOS:000281006600002 PM 20716750 ER PT J AU Keebler, ME Deo, RC Surti, A Konieczkowski, D Guiducci, C Burtt, N Buxbaum, SG Sarpong, DF Steffes, MW Wilson, JG Taylor, HA Kathiresan, S AF Keebler, Mary E. Deo, Rahul C. Surti, Aarti Konieczkowski, David Guiducci, Candace Burtt, Noel Buxbaum, Sarah G. Sarpong, Daniel F. Steffes, Michael W. Wilson, James G. Taylor, Herman A. Kathiresan, Sekar TI Fine-Mapping in African Americans of 8 Recently Discovered Genetic Loci for Plasma Lipids The Jackson Heart Study SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE lipids; genetics; epidemiology; risk factors ID GENOME-WIDE ASSOCIATION; CHOLESTEROL; ADMIXTURE; VARIANTS; DISEASE; RISK AB Background-Genome-wide association studies in cohorts of European descent have identified novel genomic regions as associated with lipids, but their relevance in African Americans remains unclear. Methods and Results-We genotyped 8 index single nucleotide polymorphisms (SNPs) and 488 tagging SNPs across 8 novel lipid loci in the Jackson Heart Study, a community-based cohort of 4605 African Americans. For each trait, we calculated residuals adjusted for age, sex, and global ancestry and performed multivariable linear regression to detect genotype-phenotype association with adjustment for local ancestry. To explore admixture effects, we conducted stratified analyses in individuals with a high probability of 2 African ancestral alleles or at least 1 European allele at each locus. We confirmed 2 index SNPs as associated with lipid traits in African Americans, with suggestive association for 3 more. However, the effect sizes for 4 of the 5 associated SNPs were larger in the European local ancestry subgroup compared with the African local ancestry subgroup, suggesting that the replication is driven by European ancestry segments. Through fine-mapping, we discovered 3 new SNPs with significant associations, 2 with consistent effect on triglyceride levels across ancestral groups: rs636523 near DOCK7/ANGPTL3 and rs780093 in GCKR. African linkage disequilibrium patterns did not assist in narrowing association signals. Conclusions-We confirm that 5 genetic regions associated with lipid traits in European-derived populations are relevant in African Americans. To further evaluate these loci, fine-mapping in larger African American cohorts and/or resequencing will be required. (Circ Cardiovasc Genet. 2010; 3: 358-364.) C1 [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Keebler, Mary E.; Surti, Aarti; Konieczkowski, David; Guiducci, Candace; Burtt, Noel; Kathiresan, Sekar] Broad Inst, Cambridge, MA USA. [Buxbaum, Sarah G.; Sarpong, Daniel F.; Taylor, Herman A.] Jackson State Univ, Jackson, MS USA. [Steffes, Michael W.] Univ Minnesota, Minneapolis, MN USA. [Wilson, James G.] GV Sonny Montgomery VA Med Ctr, Jackson, MS USA. [Wilson, James G.; Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Taylor, Herman A.] Tougaloo Coll, Tougaloo, MS USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St,CZPN 5-252, Boston, MA 02115 USA. EM skathiresan@partners.org RI Buxbaum, Sarah/E-1970-2013 OI Buxbaum, Sarah/0000-0002-4886-3564 FU NHLBI NIH HHS [N01 HC095171, K08 HL098361, K08 HL098361-01A1, K08 HL098361-02, K23 HL083102, K23 HL083102-01A1, N01 HC095170, N01 HC095172, N01-HC-95170, N01-HC-95171, N01-HC-95172, N01HC95170, N01HC95171, N01HC95172, R01 HL084107, R01 HL084107-01, R01-HL-084107]; NIGMS NIH HHS [T32 GM007753] NR 14 TC 19 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD AUG PY 2010 VL 3 IS 4 BP 358 EP U149 DI 10.1161/CIRCGENETICS.109.914267 PG 8 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 639WH UT WOS:000281006600008 PM 20570916 ER PT J AU Stein, PD Matta, F Yaekoub, AY Kazerooni, EA Cahill, JE Goodman, LR Sostman, HD Hales, CA Denier, JE Weg, JG Ghumman, D Chan, KM Woodard, PK Kwun, Y AF Stein, Paul D. Matta, Fadi Yaekoub, Abdo Y. Kazerooni, Ella A. Cahill, Jennifer Ellis Goodman, Lawrence R. Sostman, H. Dirk Hales, Charles A. Denier, James E. Weg, John G. Ghumman, Dilraj Chan, Kevin M. Woodard, Pamela K. Kwun, Yoojin TI CT Venous Phase Venography With 64-Detector CT Angiography in the Diagnosis of Acute Pulmonary Embolism SO CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS LA English DT Article DE pulmonary embolism; deep venous thrombosis; CT angiography; CT venography; 64-detector CT ID COMPUTED-TOMOGRAPHY VENOGRAPHY; THROMBOEMBOLIC DISEASE; RADIATION-EXPOSURE; PIOPED-II; MULTIDETECTOR CT; HELICAL CT; D-DIMER; THROMBOSIS; SONOGRAPHY; MANAGEMENT AB The value of computed tomographic (CT) venography in combination with CT pulmonary angiography has been questioned because of the potential dangers of radiation. Accordingly, we retrospectively evaluated the diagnostic yield of 64-detector CT angiography with CT venography. Among patients who routinely underwent CT venography with CT angiography, the CT angiogram showed acute pulmonary embolism (PE) in 206 of 1903 patients (10.8%). A positive CT venogram in a patient with a negative CT angiogram was shown in 25 of 1903 patients (1.3%). Either the CT angiogram or the CT venogram showed venous thromboembolism in 231 of 1903 patients (12.1%). The proportion of patients with venous thromboembolism diagnosed only by a CT venogram was 25 of 231 (10.8%). In conclusion, the proportion of patients with venous thromboembolism diagnosed only by a CT venogram is sufficiently high to merit consideration of its use especially in those at high risk for DVT. C1 [Stein, Paul D.; Matta, Fadi; Yaekoub, Abdo Y.; Denier, James E.; Ghumman, Dilraj] St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI USA. [Stein, Paul D.] Wayne State Univ, Dept Med, Detroit, MI 48202 USA. [Kazerooni, Ella A.; Weg, John G.; Chan, Kevin M.; Kwun, Yoojin] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Cahill, Jennifer Ellis; Hales, Charles A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Cahill, Jennifer Ellis; Hales, Charles A.] Harvard Univ, Sch Med, Boston, MA USA. [Goodman, Lawrence R.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. [Sostman, H. Dirk] Weill Cornell Med Coll, Houston, TX USA. [Sostman, H. Dirk] Methodist Hosp, Houston, TX 77030 USA. [Woodard, Pamela K.] Washington Univ, Dept Radiol, St Louis, MO USA. RP Stein, PD (reprint author), St Joseph Mercy Oakland, 44405 Woodward Ave, Pontiac, MI 48341 USA. EM steinp@trinity-health.org NR 36 TC 6 Z9 6 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1076-0296 J9 CLIN APPL THROMB-HEM JI Clin. Appl. Thromb.-Hemost. PD AUG PY 2010 VL 16 IS 4 BP 422 EP 429 DI 10.1177/1076029609335502 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 628PA UT WOS:000280131300007 PM 19520677 ER PT J AU Charles, RC Sheikh, A Krastins, B Harris, JB Bhuiyan, MS LaRocque, RC Logvinenko, T Sarracino, DA Kudva, IT Eisenstein, J Podolsky, MJ Kalsy, A Brooks, WA Ludwig, A John, M Calderwood, SB Qadri, F Ryan, ET AF Charles, Richelle C. Sheikh, Alaullah Krastins, Bryan Harris, Jason B. Bhuiyan, M. Saruar LaRocque, Regina C. Logvinenko, Tanya Sarracino, David A. Kudva, Indira T. Eisenstein, Jana Podolsky, Michael J. Kalsy, Anuj Brooks, W. Abdullah Ludwig, Albrecht John, Manohar Calderwood, Stephen B. Qadri, Firdausi Ryan, Edward T. TI Characterization of Anti-Salmonella enterica Serotype Typhi Antibody Responses in Bacteremic Bangladeshi Patients by an Immunoaffinity Proteomics-Based Technology SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID T-CELL RESPONSES; OUTER-MEMBRANE PROTEINS; C-TERMINAL DOMAIN; SYSTEM PHOP-PHOQ; SEROVAR TYPHI; ESCHERICHIA-COLI; IMMUNE-RESPONSES; HUMAN INFECTION; VIBRIO-CHOLERAE; PARATYPHI-A AB Salmonella enterica serotype Typhi is the cause of typhoid fever and a human-restricted pathogen. Currently available typhoid vaccines provide 50 to 90% protection for 2 to 5 years, and available practical diagnostic assays to identify individuals with typhoid fever lack sensitivity and/or specificity. Identifying immunogenic S. Typhi antigens expressed during human infection could lead to improved diagnostic assays and vaccines. Here we describe a platform immunoaffinity proteomics-based technology (IPT) that involves the use of columns charged with IgG, IgM, or IgA antibody fractions recovered from humans bacteremic with S. Typhi to capture S. Typhi proteins that were subsequently identified by mass spectrometry. This screening tool identifies immunogenic proteins recognized by antibodies from infected hosts. Using this technology and the plasma of patients with S. Typhi bacteremia in Bangladesh, we identified 57 proteins of S. Typhi, including proteins known to be immunogenic (PagC, HlyE, OmpA, and GroEL) and a number of proteins present in the human-restricted serotypes S. Typhi and S. Paratyphi A but rarely found in broader-host-range Salmonella spp. (HlyE, CdtB, PltA, and STY1364). We categorized identified proteins into a number of major groupings, including those involved in energy metabolism, protein synthesis, iron homeostasis, and biosynthetic and metabolic functions and those predicted to localize to the outer membrane. We assessed systemic and mucosal anti-HlyE responses in S. Typhi-infected patients and detected anti-HlyE responses at the time of clinical presentation in patients but not in controls. These findings could assist in the development of improved diagnostic assays. C1 [Charles, Richelle C.; Harris, Jason B.; LaRocque, Regina C.; Eisenstein, Jana; Podolsky, Michael J.; Kalsy, Anuj; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charles, Richelle C.; Harris, Jason B.; LaRocque, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sheikh, Alaullah; Bhuiyan, M. Saruar; Brooks, W. Abdullah; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. [Krastins, Bryan; Sarracino, David A.] Thermo Fisher Sci, Cambridge, MA USA. [Logvinenko, Tanya] Tufts Univ, Biostat Res Ctr, Med Ctr, ICRHPS, Boston, MA 02111 USA. [Kudva, Indira T.] ARS, Food Safety & Enter Pathogens Res Unit, Natl Ctr Anim Hlth, USDA, Ames, IA USA. [Ludwig, Albrecht] Klinikum Johann Wolfgang Goethe Univ, Inst Med Mikrobiol & Krankenhaushyg, Frankfurt, Germany. [John, Manohar] Pathovacs Inc, Ames, IA USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Charles, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM rccharles@partners.org FU National Institutes of Health, National Institute of Allergy and Infectious Diseases [AI072599, AI077883, AI058935, NS059429]; Johns Hopkins Bloomberg School of Public Health; Fogarty International Center [TW05572, TW05572-09S1, TW007409, TW07144]; NIAID [AI089721]; Howard Hughes Medical Institute; Deutsche Forschungsgemeinschaft [LU 842/1-1] FX This work was supported by the ICDDR, B, grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI072599 [E. T. R.], AI077883 [E. T. R.], AI058935 [R. C. C. and S. B. C.], NS059429 [J.B.H.]), the PneumoADIP Project of the Johns Hopkins Bloomberg School of Public Health (W. A. B.), an ICDDRB-US Centers for Disease Control and Prevention Cooperative Agreement (W. A. B.), a Training Grant in Vaccine Development from the Fogarty International Center, including an ARRA supplement (TW05572 [A. S., M. S. B., and F. Q.] and TW05572-09S1 [R. C. C.]), Career Development Awards (K01) from the Fogarty International Center (TW007409 [J.B.H.], TW07144 [R. C. L.]) and (K08) from the NIAID (AI089721 [R. C. C.]), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (R. C. L.), and a grant from the Deutsche Forschungsgemeinschaft (LU 842/1-1 [A. L.]). NR 57 TC 16 Z9 17 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD AUG PY 2010 VL 17 IS 8 BP 1188 EP 1195 DI 10.1128/CVI.00104-10 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 633XG UT WOS:000280539900004 PM 20573880 ER PT J AU Arndt, CAS Koshkina, NV Inwards, CY Hawkins, DS Krailo, MD Villaluna, D Anderson, PM Goorin, AM Blakely, ML Bernstein, M Bell, SA Ray, K Grendahl, DC Marina, N Kleinerman, ES AF Arndt, Carola A. S. Koshkina, Nadya V. Inwards, Carrie Y. Hawkins, Douglas S. Krailo, Mark D. Villaluna, Doojduen Anderson, Peter M. Goorin, Allen M. Blakely, Martin L. Bernstein, Mark Bell, Sharon A. Ray, Kaylee Grendahl, Darryl C. Marina, Neyssa Kleinerman, Eugenie S. TI Inhaled Granulocyte-Macrophage Colony Stimulating Factor for First Pulmonary Recurrence of Osteosarcoma: Effects on Disease-Free Survival and Immunomodulation. A Report From the Children's Oncology Group SO CLINICAL CANCER RESEARCH LA English DT Article ID EARLY LYMPHOCYTE RECOVERY; GM-CSF; AEROSOL GEMCITABINE; ANTITUMOR IMMUNITY; PROGNOSTIC-FACTORS; LUNG METASTASES; FAS EXPRESSION; CELLS; CHEMOTHERAPY; THERAPY AB Purpose: Osteosarcoma most commonly recurs in the lung. Based on preliminary data on the antitumor effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in animal models, and promising phase I trials, we embarked on a feasibility study of inhaled GM-CSF in patients with first isolated pulmonary recurrence of osteosarcoma. Experimental Design: Forty-three eligible patients received inhaled GM-CSF at doses from 250 to 1,750 mu g twice daily on alternate weeks. Following two cycles, patients underwent thoracotomy to resect tumor and analyze pulmonary nodules for expression of Fas/Fas ligand (Fas/FasL), and the presence of dendritic cells by immunostaining for CD1a, clusterin, and S100. Following surgery, patients received 12 additional cycles of therapy on alternating weeks or until progression. Event-free survival and survival, and feasibility of therapy delivery were evaluated. Results: Dose escalation to 1,750 mu g twice daily was feasible with no dose-limiting toxicity. Mean scores for Fas/FasL in nodules from patients with bilateral recurrence who underwent unilateral thoracotomy pretreatment (using a scoring system of 0-3) were 1.3 and 0.88, respectively, compared with 0.78 and 0.62 in nodules resected following two cycles of therapy. Only 11 of 30 nodules postinhalation were positive for CD1a, 4 of 30 for S100, and 6 of 30 for clusterin. Event-free and overall survival at 3 years were 7.8% and 35.4%, respectively. Conclusions: Inhalation of GM-CSF at doses from 250 to 1,750 mu g twice daily on alternate weeks was feasible with low toxicity. However, no detectable immunostimulatory effect in pulmonary metastases or improved outcome postrelapse was seen. Clin Cancer Res; 16(15); 4024-30. (C) 2010 AACR. C1 [Arndt, Carola A. S.; Inwards, Carrie Y.; Bell, Sharon A.; Grendahl, Darryl C.] Mayo Clin, Rochester, MN 55905 USA. [Koshkina, Nadya V.; Anderson, Peter M.; Kleinerman, Eugenie S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hawkins, Douglas S.] Seattle Childrens Hosp, Seattle, WA USA. [Krailo, Mark D.] Univ So Calif, Los Angeles, CA USA. [Villaluna, Doojduen] Childrens Oncol Grp, Arcadia, CA USA. [Goorin, Allen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Blakely, Martin L.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Bernstein, Mark] IWK Hlth Ctr, Halifax, NS, Canada. [Ray, Kaylee] Doernbecher Hosp Children, Portland, OR USA. [Marina, Neyssa] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Arndt, CAS (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM carndt@mayo.edu FU [U10 CA98543]; [U10 CA98413] FX Grant U10 CA98543 and U10 CA98413. NR 30 TC 26 Z9 29 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2010 VL 16 IS 15 BP 4024 EP 4030 DI 10.1158/1078-0432.CCR-10-0662 PG 7 WC Oncology SC Oncology GA 633TT UT WOS:000280530300023 PM 20576718 ER PT J AU Refaat, MM Hashash, JG Shalaby, AA AF Refaat, Marwan M. Hashash, Jana G. Shalaby, Alaa A. TI Late Perforation by Cardiac Implantable Electronic Device Leads: Clinical Presentation, Diagnostic Clues, and Management SO CLINICAL CARDIOLOGY LA English DT Review ID RIGHT-VENTRICULAR PERFORATION; PERMANENT PACEMAKER LEAD; OF-THE-LITERATURE; CARDIOVERTER-DEFIBRILLATOR; ICD LEAD; SUBCUTANEOUS TISSUES; DELAYED PERFORATION; LUNG PERFORATION; EXTRACTION; HEART AB Late intracardiac lead perforation is defined as migration and perforation of an implanted lead after 1 month of cardiac electronic device implantation. It is an under-recognized complication with significant morbidity and mortality, particularly if not recognized early. Two patients with late perforation caused by passive-fixation leads are reported and the clinical features of their presentation and management are reviewed. We conducted a thorough review of the available English language literature pertaining to this complication to draw relevant conclusions regarding presentation, diagnosis, and management. Early recognition of this complication is important as the indications for and numbers of patients who receive cardiac implantable electronic devices continue to expand. C1 [Refaat, Marwan M.; Shalaby, Alaa A.] VA Pittsburgh Healthcare Syst, Div Cardiol, Pittsburgh, PA 15240 USA. [Hashash, Jana G.] Univ Pittsburgh, Dept Internal Med, Med Ctr, Pittsburgh, PA USA. RP Shalaby, AA (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr Div, 111C-U, Pittsburgh, PA 15240 USA. EM alaa.shalaby@va.gov NR 41 TC 20 Z9 21 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD AUG PY 2010 VL 33 IS 8 BP 466 EP 475 DI 10.1002/clc.20803 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645RM UT WOS:000281482200002 PM 20734443 ER PT J AU Zerilli, F Bonanno, C Shehi, E Amicarelli, G Adlerstein, D Makrigiorgos, GM AF Zerilli, Francesco Bonanno, Cinzia Shehi, Erlet Amicarelli, Giulia Adlerstein, Daniel Makrigiorgos, G. Mike TI Methylation-Specific Loop-Mediated Isothermal Amplification for Detecting Hypermethylated DNA in Simplex and Multiplex Formats SO CLINICAL CHEMISTRY LA English DT Article ID CELL LUNG-CANCER; GENE; EPIGENETICS; BIOMARKERS; VIRUS; TUMOR; ASSAY; PCR AB BACKGROUND: Aberrant DNA methylation of gene promoters and the associated silencing of tumor suppressor genes are recognized as mechanisms contributing to tumor development. Therefore, detection of promoter hypermethylation is becoming important for diagnosis, prognosis, and aiding the design of cancer therapies. We describe a novel isothermal method for the detection of DNA hypermethylation. METHODS: Methylation-specific loop-mediated isothermal amplification (MS-LAMP) is a novel adaptation of LAMP. MS-LAMP was used for the highly specific detection of hypermethylated CpGs in the promoters of the CDKN2A [cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)], GATA5 (GATA binding protein 5), and DAPK1 (death-associated protein kinase 1) genes. The reactions occurred under isothermal conditions with 3 primer sets specific for methylated promoters. Both turbidimetry and fluorescence were used for detection. The MS-LAMP assay was validated with bisulfite-treated plasmid and genomic DNA controls of known methylation status and was applied to detect hypermethylation in 18 clinical tumor samples. A multiplex MS-LAMP for CDKN2A, GATA5, and DAPK1 was also validated with the aid of synthetic positive and negative controls. RESULTS: The MS-LAMP assay showed high specificity with plasmid and genomic DNA targets in reactions carried out in <1 h. The assay had a detection limit of approximately 30 copies of methylated target sequence and a selectivity of 0.5% methylated DNA in a mixture with unmethylated DNA. Compared with methylation-specific PCR, the MS-LAMP assay detected lower rates of methylation in lung adenocarcinoma samples. Simultaneous multiplex detection of hypermethylation in the 3 targets (CDKN2A, GATA5, and DAPK1) was readily achieved with the MS-LAMP assay in both the turbidimetric and fluorescence detection formats. CONCLUSIONS: MS-LAMP provides a highly specific isothermal method for methylation detection and is well suited for multiplex approaches. (C) 2010 American Association for Clinical Chemistry C1 [Zerilli, Francesco] Univ Milano Bicocca, Dipartimento Biotecnol & Biosci, Milan, Italy. [Bonanno, Cinzia; Shehi, Erlet; Amicarelli, Giulia; Adlerstein, Daniel] DiaSorin SpA, Saluggia, VC, Italy. [Makrigiorgos, G. Mike] Dana Farber Brigham & Womens Canc Ctr, Div Med Phys & Biophys, Dept Radiat Oncol, Boston, MA USA. [Makrigiorgos, G. Mike] Dana Farber Brigham & Womens Canc Ctr, Div Genome Stabil & DNA Repair, Boston, MA USA. RP Adlerstein, D (reprint author), Biotrin Ltd, 93 Rise, Mt Merrion, Co Dublin, Ireland. EM daniel.adlerstein@biotrin.ie NR 33 TC 14 Z9 15 U1 4 U2 17 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 AUG PY 2010 VL 56 IS 8 BP 1287 EP 1296 DI 10.1373/clinchem.2010.143545 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 633KP UT WOS:000280501400017 PM 20551384 ER PT J AU Melmed, GY Spiegel, BM Bressler, B Cheifetz, AS Devlin, SM Harrell, LE Irving, PM Jones, J Kaplan, GG Kozuch, PL Velayos, FS Baidoo, L Sparrow, MP Siegel, CA AF Melmed, Gil Y. Spiegel, Brennan M. Bressler, Brian Cheifetz, Adam S. Devlin, Shane M. Harrell, Laura E. Irving, Peter M. Jones, Jennifer Kaplan, Gilaad G. Kozuch, Patricia L. Velayos, Fernando S. Baidoo, Leonard Sparrow, Miles P. Siegel, Corey A. TI The Appropriateness of Concomitant Immunomodulators With Anti-Tumor Necrosis Factor Agents for Crohn's Disease: One Size Does Not Fit All SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Crohn's Disease; Inflammatory Bowel Disease; Infliximab; Adalimumab; Certolizumab; Anti-Tumor Necrosis alpha Therapy ID INFLAMMATORY-BOWEL-DISEASE; T-CELL LYMPHOMA; MAINTENANCE INFLIXIMAB; CERTOLIZUMAB PEGOL; RANDOMIZED-TRIAL; THERAPY; ADALIMUMAB; EFFICACY AB BACKGROUND & AIMS: There is no consensus on the appropriateness of concomitant immunomodulators with antitumor necrosis factor (TNF) therapy for Crohn's disease Some patients benefit from concomitant immunomodulators, but concerns related to infections and lymphoma risk have dampened enthusiasm for this approach We applied the RAND/University of California Los Angeles Appropriateness Method toward establishing appropriateness of concomitant immunomodulators and anti-TNF therapies for Crohn's disease METHODS: A literature review was conducted regarding efficacy and safety of concomitant immunomodulators in the setting of anti-TNF therapy for Crohn's disease and presented to the Building Research in Inflammatory Bowel Disease Globally group, a globally diverse panel of 13 gastroenterologists clinically experienced in inflammatory bowel disease A total of 134 scenarios were constructed using several clinical variables Panelists used a modified Delphi method to rate the appropriateness of concomitant immunomodulators, and met to discuss and re-rate appropriateness Disagreement was assessed using a validated index RESULTS: Concomitant immunomodulators were generally rated appropriate for 63 scenarios, uncertain for 60 scenarios, and inappropriate for 11 scenarios In general, concomitant immunomodulators were appropriate for those with extensive disease, shorter duration of disease, perianal involvement, prior surgery, females, and older patients (>26 y) Concomitant immunomodulators were generally rated inappropriate for young males, and in some scenarios involving uncomplicated disease Smoking and the particular anti-TNF medication did not Influence ratings Disagreement was observed in 6 of 134 scenarios CONCLUSIONS: The appropriateness of concomitant immunomodulators with anti-TNF therapy for Crohn's disease was determined through a modified Delphi panel approach based on expert interpretation of the available literature. Clinicians should consider multiple factors when considering concomitant immunomodulators with anti-TNF treatment. C1 [Melmed, Gil Y.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Spiegel, Brennan M.] Univ Calif Los Angeles, Los Angeles Vet Adm Ctr Outcomes Res & Educ, VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ,Digest Dis Res Ctr, Los Angeles, CA USA. [Melmed, Gil Y.; Spiegel, Brennan M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bressler, Brian] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Cheifetz, Adam S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Devlin, Shane M.; Kaplan, Gilaad G.] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Harrell, Laura E.] Univ Chicago, Chicago, IL 60637 USA. [Irving, Peter M.] Guys Hosp, London SE1 9RT, England. [Irving, Peter M.] St Thomas Hosp, London, England. [Jones, Jennifer] Univ Saskatchewan, Saskatoon, SK, Canada. [Kozuch, Patricia L.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Velayos, Fernando S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Baidoo, Leonard] Univ Pittsburgh, Pittsburgh, PA USA. [Sparrow, Miles P.] Alfred Hosp, Dept Gastroenterol, Melbourne, Vic, Australia. [Siegel, Corey A.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Melmed, GY (reprint author), Cedars Sinai Med Ctr, 8635 W 3rd St,960-W, Los Angeles, CA 90048 USA. OI kozuch, patricia/0000-0002-7465-9671; Kaplan, Gilaad/0000-0003-2719-0556 FU Centocor; Setpoint; Amgen; Celgene; Elan; PG; AstraZeneca; Bristol Meyer Squibb; Salix; Takeda; Rose Pharmaceuticals; Prometheus; Schering-Plough Canada; UCB Pharma; Shire; Abbott; Ferring Pharmaceuticals; Abbott Pharmaceuticals; Proctor and Gamble Pharmaceuticals; Crohn's and Colitis Foundation of America; National Institute of Diabetes and Digestive and Kidney Diseases [K23DK078678]; National Institutes of Health/NCRR/OD [KL2 RR024130] FX These authors disclose the following: Gil Melmed was a consultant and/or received research support from Centocor, Setpoint, Amgen, and Celgene, was on the speakers bureaus of Abbott. P&G. and Shire, and was on the advisory board of UCB: Corey Siegel was on the advisory boards of Abbott. UCB, and P&G, was a consultant and received research support from Elan and P&G. and performed CME activities for Abbott and UCB; Brennan Spiegel received research funding from AstraZeneca, Amgen, Bristol Meyer Squibb, Salix, Takeda, Rose Pharmaceuticals, and Prometheus, and was on the advisory Boards of Takeda. Prometheus, and Ironwood, Brian Bressler was on the advisory boards of Abbott. Schering-Plough Canada, UCB, Shire. P&G. and Ferring, and was on the speaker's bureaus of Abbott, Schering-Plough Canada, and Shire. Adam Cheifetz was on the speaker's bureau of Centocor, UCB, and Abbott, and the advisory boards of Abbott and UCB. Jennifer Jones was a consultant, on the speaker's bureaus, and received educational funding from Schering-Plough Canada, UCB Pharma, Shire, P&G, and Abbott. Miles Sparrow received research support from Ferring Pharmaceuticals and Abbott Pharmaceuticals, and was on the advisory board of Schering-Plough Pharmaceuticals; Fernando Velayos was on the speaker's bureau of Centocor, Peter Irving was on the advisory board and speaker's bureau of Abbott; Shane Devlin was on the speaker's bureaus for Schering-Plough and Abbott, and on the advisory boards for Abbott, Centocor, and UCB; Gilaad Kaplan was on the advisory boards of Schering-Plough. Abbott, UCB, and Shire. and Laura Harrell was a consultant for Abbott The remaining authors disclose no conflicts.; Unrestricted funding for the in-person Dallas RAND Appropriateness Panel meeting generously was provided by Proctor and Gamble Pharmaceuticals Unrestricted funding for the Building Research in Inflammatory Bowel Disease Globally group is provided by Abbott, Shire, and Proctor and Gamble Pharmaceuticals,; Dr Kaplan is a Canadian Institutes of Health Research New Investigator and an Alberta Heritage Foundation for Medical Research Population Health Investigator; Dr Harrell is supported by a Crohn's and Colitis Foundation of America Career Development Award: Dr Siegel is supported by a Crohn's and Colitis Foundation of America Career Development Award and by grant number K23DK078678 from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr Velayos is supported by a Crohn's and Colitis Foundation of America Career Development Award and the National Institutes of Health/NCRR/OD UCSF-CTSI award (KL2 RR024130) NR 20 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD AUG PY 2010 VL 8 IS 8 BP 655 EP 659 DI 10.1016/j.cgh.2010.04.023 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 638YX UT WOS:000280938200007 PM 20451665 ER PT J AU Kanwal, F Kramer, J Asch, SM El-Serag, H Spiegel, BMR Edmundowicz, S Sanyal, AJ Dominitz, JA McQuaid, KR Martin, P Keeffe, EB Friedman, LS Ho, SB Durazo, F Bacon, BR AF Kanwal, Fasiha Kramer, Jennifer Asch, Steven M. El-Serag, Hashem Spiegel, Brennan M. R. Edmundowicz, Steven Sanyal, Arun J. Dominitz, Jason A. McQuaid, Kenneth R. Martin, Paul Keeffe, Emmet B. Friedman, Lawrence S. Ho, Samuel B. Durazo, Francisco Bacon, Bruce R. TI An Explicit Quality Indicator Set for Measurement of Quality of Care in Patients With Cirrhosis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Quality of Care; Cirrhosis; Delphi Panel; Performance Measures ID PORTAL-HYPERTENSION; LIVER-TRANSPLANTATION; RHEUMATOID-ARTHRITIS; VARICEAL HEMORRHAGE; ADULT PATIENTS; MANAGEMENT; GUIDELINES; DIAGNOSIS; WORKSHOP; ASCITES AB BACKGROUND & AIMS: Cirrhosis is a prevalent and expensive condition With an increasing emphasis on quality in health care and recognition of inconsistencies in the management of patients with cirrhosis, we established a set of explicit quality indicators (QIs) for their treatment METHODS: We organized an 11-member, multidisciplinary expert panel and followed modified Delphi methods to systematically identify a set of QIs for cirrhosis We provided the panel with a report that summarized the results of a comprehensive literature review of data linking candidate QIs to outcomes The panel performed independent ratings of each candidate QI by using a standard 9-point RAND appropriateness scale (RAS) (ranging from 1 = not appropriate to 9 = most appropriate) The panel members then met, reviewed the ratings, and voted again by using an iterative process of discussion The final set of QIs was selected, QIs had a median RAS >7, and panel members agreed on those selected RESULTS: Among 169 candidate QIs, the panel rated 41 QIs as valid measures of quality care The selected QIs cover 6 domains of care including ascites (13 QIs), variceal bleeding (18 QIs), hepatic encephalopathy (4 QIs), hepatocellular cancer (1 QI), liver transplantation (2 QIs), and general cirrhosis care (3 QIs) Content coverage included prevention, diagnosis, treatment, timeliness, and follow-up CONCLUSIONS: We developed an explicit set of evidence-based QIs for treatment of cirrhosis. These provide physicians and institutions with a tool to identify processes amenable to quality improvement. This tool is intended to be applicable in any setting where care for patients with cirrhosis is provided. C1 [Kanwal, Fasiha] St Louis Vet Adm VA, St Louis, MO USA. [Kanwal, Fasiha; Bacon, Bruce R.] St Louis Univ, Sch Med, Dept Gastroenterol & Hepatol, St Louis, MO 63141 USA. [Kramer, Jennifer; El-Serag, Hashem] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kramer, Jennifer; El-Serag, Hashem] Baylor Coll Med, Dept Med, Div Gastroenterol, Houston, TX 77030 USA. [Asch, Steven M.; Spiegel, Brennan M. R.] Greater Los Angeles VA Healthcare Syst, Dept Med & Hlth Serv Res, Los Angeles, CA USA. [Asch, Steven M.; Spiegel, Brennan M. R.; Durazo, Francisco] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Edmundowicz, Steven] Washington Univ, Sch Med, St Louis, MO USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Med Ctr, Dept Internal Med, Div Gastroenterol Hepatol & Nutr, Richmond, VA USA. [Dominitz, Jason A.] Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [McQuaid, Kenneth R.] Univ Calif San Francisco, Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [McQuaid, Kenneth R.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Martin, Paul] Univ Miami, Sch Med, Div Gastroenterol & Hepatol, Miami, FL USA. [Keeffe, Emmet B.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA USA. [Ho, Samuel B.] VA San Diego Healthcare Syst, Dept Med, San Diego, CA USA. [Ho, Samuel B.] Univ Calif San Diego, San Diego, CA 92103 USA. [Durazo, Francisco] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Dumont Liver Transplant Ctr, Los Angeles, CA 90095 USA. RP Kanwal, F (reprint author), St Louis VA Med Ctr, 915 N Grand,111 JC GI, St Louis, MO 63141 USA. EM fkanwal@yahoo.com OI Edmundowicz, Steven/0000-0002-6541-3485; Dominitz, Jason/0000-0002-8070-7086 FU American Society for Gastrointestinal Endoscopy; American College of Gastroenterology FX This material is based on work supported by the 2008 American Society for Gastrointestinal Endoscopy Quality of Care Award and by the 2009 American College of Gastroenterology Clinical Research Award. NR 31 TC 45 Z9 45 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD AUG PY 2010 VL 8 IS 8 BP 709 EP 717 DI 10.1016/j.cgh.2010.03.028 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 638YX UT WOS:000280938200016 PM 20385251 ER PT J AU Simchowitz, B Shiman, L Spencer, J Brouillard, D Gross, A Connor, M Weingart, SN AF Simchowitz, Brett Shiman, Lawrence Spencer, Justin Brouillard, Daniela Gross, Anne Connor, Maureen Weingart, Saul N. TI Perceptions and Experiences of Patients Receiving Oral Chemotherapy SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID METASTATIC COLORECTAL-CANCER; INTRAVENOUS FLUOROURACIL; PALLIATIVE CHEMOTHERAPY; SAFETY PROFILE; PHASE-III; THERAPY; LEUCOVORIN; CAPECITABINE AB Although many patients prefer orally administered cancer therapy (including oral chemotherapy) because of its convenience, the shift from hospital to home-based administration creates concerns. This article explores the perceptions and experiences of oral chemotherapy users and their caregivers to assess vulnerabilities and improvement opportunities at each stage of the medication process: choosing oral chemotherapy, prescribing, dispensing, administering, and monitoring. The authors recruited 15 current and former oral chemotherapy users, as well as caregivers who administered the medications to children, to participate in one of two focus group sessions at a comprehensive cancer center. Participants largely were satisfied with oral cancer therapy but raised concerns regarding their lack of preparedness for side effects and their unfamiliarity with the possible techniques to mitigate drug toxicity. Participants also described difficulties obtaining medications through retail pharmacies. Parents of pediatric patients with cancer indicated concerns regarding their children's emotional health and correct medication administration. Participants believed that the initial prescribing encounter should have included more education, and they also wanted more frequent follow-up by healthcare practitioners. As oral cancer therapy is used more widely, oncology healthcare providers will need to create robust mechanisms to support their safe use. C1 [Brouillard, Daniela; Gross, Anne; Weingart, Saul N.] Dana Farber Canc Inst, Adult Ambulatory Serv, Boston, MA 02115 USA. [Simchowitz, Brett] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Connor, Maureen] Qual & Patient Safety Consultant, Arlington, MA USA. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Adult Ambulatory Serv, Boston, MA 02115 USA. FU U.S. Agency for Healthcare Research and Quality [1 P20HS017123] FX The authors take full responsibility for the content of the article. The study was supported by a grant from the U.S. Agency for Healthcare Research and Quality (grant # 1 P20HS017123). The authors did not receive honoraria for this work. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or editorial staff. NR 19 TC 16 Z9 16 U1 1 U2 11 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD AUG PY 2010 VL 14 IS 4 BP 447 EP 453 DI 10.1188/10.CJON.447-453 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 636NK UT WOS:000280743800011 PM 20682500 ER PT J AU Walsh, MC AF Walsh, Michele C. TI Impact of Treatment-Related Cardiac Toxicity on Lymphoma Survivors: An Institutional Approach for Risk Reduction and Management SO CLINICAL JOURNAL OF ONCOLOGY NURSING LA English DT Article ID LONG-TERM SURVIVORS; QUALITY-OF-LIFE; HODGKINS-DISEASE; CARE PLANS; CARDIOMYOPATHY; THERAPY; CHEST AB Despite improvements in treatment and overall survival rates, survivors of lymphoma may have long-term and late effects. Given the immense risk for cardiac disease after treatment for Hodgkin lymphoma and non-Hodgkin lymphoma, healthcare providers should focus on prevention of secondary adverse effects. The Dana-Farber Cancer Institute has been working to develop guidelines to address the cardiotoxicities that impact the lymphoma survivor population. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Walsh, MC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM michele_walsh@dfci.harvard.edu NR 24 TC 0 Z9 0 U1 1 U2 1 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 1092-1095 J9 CLIN J ONCOL NURS JI Clin. J. Oncol. Nurs. PD AUG PY 2010 VL 14 IS 4 BP 505 EP 507 DI 10.1188/10.CJON.505-507 PG 3 WC Oncology; Nursing SC Oncology; Nursing GA 636NK UT WOS:000280743800018 PM 20682507 ER PT J AU Schroen, AT Petroni, GR Wang, H Gray, R Wang, XFF Cronin, W Sargent, DJ Benedetti, J Wickerham, DL Djulbegovic, B Slingluff, CL AF Schroen, Anneke T. Petroni, Gina R. Wang, Hongkun Gray, Robert Wang, Xiaofei F. Cronin, Walter Sargent, Daniel J. Benedetti, Jacqueline Wickerham, Donald L. Djulbegovic, Benjamin Slingluff, Craig L., Jr. TI Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials SO CLINICAL TRIALS LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; CANCER CLINICAL-TRIALS; PARTICIPATION; BARRIERS; ENROLLMENT; ATTITUDES AB Background A major challenge for randomized phase III oncology trials is the frequent low rates of patient enrollment, resulting in high rates of premature closure due to insufficient accrual. Purpose We conducted a pilot study to determine the extent of trial closure due to poor accrual, feasibility of identifying trial factors associated with sufficient accrual, impact of redesign strategies on trial accrual, and accrual benchmarks designating high failure risk in the clinical trials cooperative group (CTCG) setting. Methods A subset of phase III trials opened by five CTCGs between August 1991 and March 2004 was evaluated. Design elements, experimental agents, redesign strategies, and pretrial accrual assessment supporting accrual predictions were abstracted from CTCG documents. Percent actual/predicted accrual rate averaged per month was calculated. Trials were categorized as having sufficient or insufficient accrual based on reason for trial termination. Analyses included univariate and bivariate summaries to identify potential trial factors associated with accrual sufficiency. Results Among 40 trials from one CTCG, 21 (52.5%) trials closed due to insufficient accrual. In 82 trials from five CTCGs, therapeutic trials accrued sufficiently more often than nontherapeutic trials (59% vs 27%, p = 0.05). Trials including pretrial accrual assessment more often achieved sufficient accrual than those without (67% vs 47%, p = 0.08). Fewer exclusion criteria, shorter consent forms, other CTCG participation, and trial design simplicity were not associated with achieving sufficient accrual. Trials accruing at a rate much lower than predicted (< 35% actual/predicted accrual rate) were consistently closed due to insufficient accrual. Limitations This trial subset under-represents certain experimental modalities. Data sources do not allow accounting for all factors potentially related to accrual success. Conclusion Trial closure due to insufficient accrual is common. Certain trial design factors appear associated with attaining sufficient accrual. Defining accrual benchmarks for early trial termination or redesign is feasible, but better accrual prediction methods are critically needed. Future studies should focus on identifying trial factors that allow more accurate accrual predictions and strategies that can salvage open trials experiencing slow accrual. Clinical Trials 2010; 7: 312-321. http://ctj.sagepub.com. C1 [Schroen, Anneke T.; Slingluff, Craig L., Jr.] Univ Virginia, Dept Surg, Charlottesville, VA 22903 USA. [Petroni, Gina R.; Wang, Hongkun] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Gray, Robert] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Wang, Xiaofei F.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Cronin, Walter; Wickerham, Donald L.] NSABP Operat Ctr, Pittsburgh, PA USA. [Sargent, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Benedetti, Jacqueline] SW Oncol Grp Stat Ctr, Seattle, WA USA. [Djulbegovic, Benjamin] Univ S Florida, Dept Med, Tampa, FL USA. RP Schroen, AT (reprint author), Univ Virginia, Dept Surg, Charlottesville, VA 22903 USA. EM ats2x@virginia.edu RI Djulbegovic, Benjamin/I-3661-2012; OI Djulbegovic, Benjamin/0000-0003-0671-1447; Sargent, Daniel/0000-0002-2684-4741 FU Commonwealth Foundation for Cancer Research FX This research was supported by the Commonwealth Foundation for Cancer Research support to the University of Virginia Cancer Center. NR 23 TC 34 Z9 34 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD AUG PY 2010 VL 7 IS 4 BP 312 EP 321 DI 10.1177/1740774510374973 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636MV UT WOS:000280741400002 PM 20595245 ER PT J AU Yeh, HC Clark, JM Emmons, KE Moore, RH Bennett, GG Warner, ET Sarwer, DB Jerome, GJ Miller, ER Volger, S Louis, TA Wells, B Wadden, TA Colditz, GA Appel, LJ AF Yeh, Hsin-Chieh Clark, Jeanne M. Emmons, Karen E. Moore, Renee H. Bennett, Gary G. Warner, Erica T. Sarwer, David B. Jerome, Gerald J. Miller, Edgar R., III Volger, Sheri Louis, Thomas A. Wells, Barbara Wadden, Thomas A. Colditz, Graham A. Appel, Lawrence J. TI Independent but coordinated trials: insights from the Practice-based Opportunities for Weight Reduction Trials Collaborative Research Group SO CLINICAL TRIALS LA English DT Article ID UNITED-STATES; RANDOMIZED-TRIAL; OBESITY; INTERVENTIONS; OVERWEIGHT; ADULTS AB Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the 'Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.' Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. Methods The Collaborative Research Group consists of three individual studies: 'Be Fit, Be Well' (Washington University in St. Louis/Harvard University), 'POWER Hopkins' (Johns Hopkins), and 'POWER-UP' (University of Pennsylvania). There are a total of 15 participating clinics with similar to 1100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. Limitations The challenges of the organizational design include the complex decision-making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. C1 [Yeh, Hsin-Chieh] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Dept Med, Baltimore, MD 21218 USA. [Yeh, Hsin-Chieh; Clark, Jeanne M.; Miller, Edgar R., III; Appel, Lawrence J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Emmons, Karen E.; Bennett, Gary G.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Emmons, Karen E.; Bennett, Gary G.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Moore, Renee H.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Moore, Renee H.; Sarwer, David B.; Volger, Sheri; Wadden, Thomas A.] Univ Penn, Dept Psychiat, Ctr Weight & Eating Disorders, Philadelphia, PA 19104 USA. [Bennett, Gary G.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA. [Bennett, Gary G.] Duke Univ, Duke Global Hlth Inst, Durham, NC USA. [Warner, Erica T.; Colditz, Graham A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Jerome, Gerald J.] Towson Univ, Dept Kinesiol, Towson, MD USA. [Louis, Thomas A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Wells, Barbara] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Colditz, Graham A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Colditz, Graham A.] Washington Univ, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Appel, Lawrence J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. RP Yeh, HC (reprint author), Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Dept Med, Baltimore, MD 21218 USA. EM hyeh1@jhmi.edu RI Colditz, Graham/A-3963-2009; OI volger, sheri/0000-0002-1689-1173; Colditz, Graham/0000-0002-7307-0291; Jerome, Gerald/0000-0003-0612-2626 FU NHLBI [U01HL087071, U01HL087085, U01HL087072, NCT00661817, NCT00783315, NCT00826774] FX The POWER Trials Collaborative Research Group is supported by NHLBI grants: U01HL087071 (Washington University), U01HL087085 (Johns Hopkins University), and U01HL087072 (University of Pennsylvania). The ClinicalTrials.gov identifiers are NCT00661817 (Washington University), NCT00783315 (Johns Hopkins University), and NCT00826774 (University of Pennsylvania). NR 15 TC 25 Z9 25 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD AUG PY 2010 VL 7 IS 4 BP 322 EP 332 DI 10.1177/1740774510374213 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 636MV UT WOS:000280741400003 PM 20573639 ER PT J AU Chang, KM AF Chang, Kyong-Mi TI Hepatitis B Immunology for Clinicians SO CLINICS IN LIVER DISEASE LA English DT Article DE Hepatitis B; Innate immunity; Adaptive immunity; Regulatory T cells; Costimulation; Pathogenesis; Programmed death 1 ID REGULATORY T-CELLS; PLASMACYTOID DENDRITIC CELLS; NATURAL-KILLER-CELLS; ADAPTIVE IMMUNE-RESPONSES; ACUTE VIRAL-HEPATITIS; CHRONIC HBV INFECTION; VIRUS-INFECTION; LIVER-DAMAGE; LYMPHOCYTE RESPONSE; ANTIVIRAL THERAPY AB Hepatitis B virus (HBV) is a hepatotrophic DNA virus that causes acute and chronic hepatitis. Despite an effective vaccine, more than 350 million people are chronically infected with HBV worldwide and are at risk for progressive liver disease. There are marked geographic variations in HBV prevalence (ranging from 0.1% to 2% in low prevalence areas and 10% to 20% in high prevalence areas) related to the timing and mode of HBV exposure. In many developed countries, HBV exposure typically occurs in adults via sexual transmission with a low chronicity rate (5%). In regions with high HBV prevalence (eg, Asia, sub-Saharan Africa), HBV exposure tends to occur in the perinatal period (eg, vertical transmission from mother to infant) with a high rate of persistence in the absence of timely vaccination. The course of viral infection is defined by the interplay between the virus and host immune defense. This article introduces the innate and adaptive immune defense mechanisms in general and as related to HBV. In particular, the current concepts regarding the innate and adaptive immune components contributing to the clinical, virologic and therapeutic outcome in acute and chronic hepatitis B are examined. C1 [Chang, Kyong-Mi] Philadelphia VA Med Ctr, Div Gastroenterol, Philadelphia, PA 19104 USA. [Chang, Kyong-Mi] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Chang, KM (reprint author), Philadelphia VA Med Ctr, Div Gastroenterol, A412-A424 Med Res Bldg, Philadelphia, PA 19104 USA. EM kmchang@mail.med.upenn.edu FU NIH [UO1 DK082866, RO1 AI047519] FX This work was supported in part by NIH UO1 DK082866 and NIH RO1 AI047519 NR 82 TC 7 Z9 7 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 1089-3261 J9 CLIN LIVER DIS JI Clin. Liver Dis. PD AUG PY 2010 VL 14 IS 3 BP 409 EP + DI 10.1016/j.cld.2010.05.012 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 639OP UT WOS:000280984400004 PM 20638022 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI My Mother's Levetiracetam SO CNS SPECTRUMS LA English DT Editorial Material C1 [Nierenberg, Andrew A.] Harvard Univ, Psychiat, Sch Med, Cambridge, MA 02138 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Psychiat, Sch Med, Cambridge, MA 02138 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD AUG PY 2010 VL 15 IS 8 BP 487 EP 488 DI 10.1017/S1092852900000419 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA V44BS UT WOS:000209725100001 PM 20703195 ER PT J AU Dording, CM Mischoulon, D Goodness, TM Baer, L Clain, A Stewart, JW Matthews, JD McGrath, PJ Nierenberg, AA Fava, M Papakostas, GI AF Dording, Christina M. Mischoulon, David Goodness, Tracie M. Baer, Lee Clain, Alisabet Stewart, Jonathan W. Matthews, John D. McGrath, Patrick J. Nierenberg, Andrew A. Fava, Maurizio Papakostas, George I. TI Psychoticism and Paranoid Ideation in Patients With Nonpsychotic Major Depressive Disorder: Prevalence, Response to Treatment, and Impact on Short- and Long-Term Treatment Outcome SO CNS SPECTRUMS LA English DT Article AB Objective/Introduction: We sought to characterize the impact of the 90-item Symptom Checklist (SCL-90) subscales for paranoid ideation (PI) and psychoticism (P) in patients with major depressive disorder (MDD), on acute antidepressant response and on relapse prevention. Methods: Subjects with Structured Clinical Interview for DSM Disorders-diagnosed non psychotic MDD were recruited into a clinical trial of open-label fluoxetine 10-60 mg/day for 12 weeks, followed by double-blind randomization of responders (n=262) to fluoxetine continuation or placebo for 12 months. PI and P were assessed with the patient-rated SCL-90. The association of these symptoms with response to treatment was assessed by logistic regression. Results: We found significant decreases in PI and P during acute treatment phase for fluoxetine responders and nonresponders, although only 10.3% and 7.5% of patients experienced a >50% reduction in PI and P scores, respectively. Neither PI nor P scores significantly predicted time to relapse. P scores predicted a lower response rate to treatment with fluoxetine. Discussion:The results of the present study suggest that there is a significant relationship between the presence of psychoticism in patients with nonpsychotic MDD, and the likelihood of overall depressive symptom improvement following a trial of monotherapy with fluoxetine. Conclusion: An increased burden of psychoticism in depressed subjects may confer poorer response to fluoxetine, but not increased risk of relapse among fluoxetine responders. C1 [Dording, Christina M.] Harvard Univ, Sch Med, Sexual Behav Studies, Boston, MA USA. [Dording, Christina M.; Mischoulon, David; Nierenberg, Andrew A.; Fava, Maurizio; Papakostas, George I.] Harvard Univ, Sch Med, Psychiat, Boston, MA USA. [Mischoulon, David] Massachusetts Gen Hosp, Res, Boston, MA 02114 USA. [Mischoulon, David] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA. [Goodness, Tracie M.; Clain, Alisabet; Nierenberg, Andrew A.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Baer, Lee] Harvard Univ, Sch Med, Psychol, Boston, MA USA. [Baer, Lee] Massachusetts Gen Hosp, Dept Psychiat, Psychol, Boston, MA 02114 USA. [Stewart, Jonathan W.; McGrath, Patrick J.] Columbia Univ Coll Phys & Surg, Psychiat Clin, 630 W 168th St, New York, NY 10032 USA. [Stewart, Jonathan W.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Matthews, John D.] Massachusetts Gen Hosp, Inpatient Res & Training, Boston, MA USA. [Matthews, John D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [McGrath, Patrick J.] New York State Psychiat Inst & Hosp, Depress Evaluat Serv, New York, NY 10032 USA. [Nierenberg, Andrew A.] NIMH, Bipolar Trials Network, Bethesda, MD USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA USA. [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Res Program, Boston, MA USA. [Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA. [Papakostas, George I.] Massachusetts Gen Hosp, Treatment Resistant Depress Studies, Boston, MA 02114 USA. RP Dording, CM (reprint author), Massachusetts Gen Hosp, 50 Staniford St,401, Boston, MA 02114 USA. EM cdording@partners.org NR 34 TC 0 Z9 0 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1092-8529 EI 2165-6509 J9 CNS SPECTRUMS JI CNS Spectr. PD AUG PY 2010 VL 15 IS 8 BP 515 EP 521 DI 10.1017/S1092852900000468 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA V44BS UT WOS:000209725100006 PM 20703198 ER PT J AU Greenberg, JL Wilhelm, S AF Greenberg, Jennifer L. Wilhelm, Sabine TI SPECIAL SERIES: COGNITIVE-BEHAVIORAL TREATMENT OF BODY IMAGE DISORDERS Introduction SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Editorial Material ID DYSMORPHIC DISORDER; EATING-DISORDERS; VISUAL-ATTENTION; PREVALENCE; WOMEN; DISTURBANCE; POPULATION; SAMPLE; PARTS; BIAS C1 [Wilhelm, Sabine] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenberg, Jennifer L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM wilhelm@psych.mgh.harvard.edu NR 29 TC 1 Z9 1 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD AUG PY 2010 VL 17 IS 3 BP 237 EP 240 PG 4 WC Psychology, Clinical SC Psychology GA 615PU UT WOS:000279148000001 ER PT J AU Wilhelm, S Buhlmann, U Hayward, LC Greenberg, JL Dimaite, R AF Wilhelm, Sabine Buhlmann, Ulrike Hayward, Laura C. Greenberg, Jennifer L. Dimaite, Ruta TI A Cognitive-Behavioral Treatment Approach for Body Dysmorphic Disorder SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; OPEN-LABEL; CLINICAL-FEATURES; IMAGINED UGLINESS; 200 INDIVIDUALS; PREVALENCE; TRIAL; COMORBIDITY; DERMATOLOGY; FLUVOXAMINE AB Although body dysmorphic disorder (BDD) has been described in the literature for mow than a century, there has been only a limited focus on the development of cognitive behavioral treatments for BDD. Our case report provides a data dad description of a course of cognitive behavioral treatment (CBT) for an individual with BDD. The patient was treated for 10 weekly 50-minute individual sessions. The treatment focused on psychoeducation cognitive restructuring, exposure and response prevention, and perceptual retraining exercises. The patient's BDD symptoms significantly improved over the course of the treatment. This case study illustrates several clinical strategies and provides further support. for CBT as a promising treatment for individuals suffering from BDD. C1 [Wilhelm, Sabine; Greenberg, Jennifer L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilhelm, Sabine; Dimaite, Ruta] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Buhlmann, Ulrike] Humboldt Univ, Berlin, Germany. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM wilhelm@psych.mgh.harvard.edu NR 44 TC 16 Z9 16 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD AUG PY 2010 VL 17 IS 3 BP 241 EP 247 PG 7 WC Psychology, Clinical SC Psychology GA 615PU UT WOS:000279148000002 ER PT J AU Greenberg, JL Markowitz, S Petronko, MR Taylor, CE Wilhelm, S Wilson, GT AF Greenberg, Jennifer L. Markowitz, Sarah Petronko, Michael R. Taylor, Caitlin E. Wilhelm, Sabine Wilson, G. Terence TI Cognitive-Behavioral Therapy for Adolescent Body Dysmorphic Disorder SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID OBSESSIVE-COMPULSIVE SCALE; RANDOMIZED CLINICAL-TRIAL; RESPONSE PREVENTION; ANXIETY DISORDERS; RELIABILITY; SERTRALINE; CHILDREN; VALIDITY; SCHIZOPHRENIA; MAINTENANCE AB The onset of appearance-related concerns associated with body dysmorphic disorder (BDD) typically occurs in adolescence, and these concerns are often severe enough to interfere with normal development and psychosocial functioning. Cognitive behavioral therapy (CBT) is an effective treatment for adults with BDD. However, no treatment studies focusing on adolescents with BDD have been conducted. The need for an. effective treatment in this population led to the development of a brief CBT protocol with family involvement. The treatment focuses on. enhancing an adolescent's quality of life through the reduction of maladaptive thoughts and behaviors, and incorporates skills training and parent training. Similar treatment packages have already been shown to be efficacious for children and adolescents with similar disorders, such as obsessive-compulsive disorder and social phobia. The following case illustrates the application of this brief CBT protocol for BDD in an adolescent, and highlights clinical considerations needed when adapting CBT for a pediatric population. Treatment was associated with clinically significant improvement in symptoms of BDD, self-esteem, depression, and quality of life. This report extends extant literature by suggesting that CBT may be a helpful treatment for adolescents with BDD. C1 [Greenberg, Jennifer L.; Markowitz, Sarah; Taylor, Caitlin E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenberg, Jennifer L.; Markowitz, Sarah; Wilhelm, Sabine] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Petronko, Michael R.; Wilson, G. Terence] Rutgers State Univ, Piscataway, NJ 08855 USA. RP Greenberg, JL (reprint author), Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA. EM jlgreenberg@partners.org NR 50 TC 15 Z9 15 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD AUG PY 2010 VL 17 IS 3 BP 248 EP 258 PG 11 WC Psychology, Clinical SC Psychology GA 615PU UT WOS:000279148000003 ER PT J AU Delinsky, SS Wilson, GT AF Delinsky, Sherrie S. Wilson, G. Terence TI Cognitive Behavior Therapy With Body Image Exposure for Bulimia Nervosa: A Case Example SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID QUESTIONNAIRE EDE-Q; EATING-DISORDERS; MIRROR EXPOSURE; SHAPE QUESTIONNAIRE; ANOREXIA-NERVOSA; DISSATISFACTION; PSYCHOTHERAPY; ADOLESCENTS; DISTURBANCE; INTERVIEW AB Cognitive behavior therapy (CBT) is an effective treatment for bulimia nervosa (BN). However, among patients with BN, symptom improvement is more pronounced for behavioral eating symptoms (i.e., bingeing and purging) than for body image disturbance, and the persistence of body image disturbance is associated with relapse. The need for more effective body image interventions led to the development of mirror exposure, which focuses on encouraging patients to view themselves in a holistic, nonjudgmental, mindful fashion. Behavioral manifestations of body image disturbance-body checking and avoidance-are also targeted in order to reduce and eliminate such behaviors and their associated preoccupation and distress. A preliminary trial of Body Image Exposure has shown. promise, but it has not yet been tested in the context of CBT for BN. The case of "Sara" illustrates the application of this targeted treatment for body image disturbance. Central clinical issues around the perceptual, cognitive, and behavioral components of body image are delineated as they arose in treatment, as are issues of motivation and compliance. Treatment was associated with improvement in eating symptoms, body image, and mood. C1 [Delinsky, Sherrie S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Delinsky, Sherrie S.] McLean Hosp, Belmont, MA USA. [Wilson, G. Terence] Rutgers State Univ, Piscataway, NJ 08855 USA. RP Delinsky, SS (reprint author), 332 Washington St,Suite 265, Wellesley, MA 02481 USA. EM sdelinsky@gmail.com RI gray, stephen/G-6729-2011 NR 41 TC 10 Z9 11 U1 5 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD AUG PY 2010 VL 17 IS 3 BP 270 EP 277 PG 8 WC Psychology, Clinical SC Psychology GA 615PU UT WOS:000279148000005 ER PT J AU Flessner, CA Penzel, F Keuthen, NJ AF Flessner, Christopher A. Penzel, Fred Keuthen, Nancy J. CA Trichotillomania Learning Ctr Sci TI Current Treatment Practices for Children and Adults With Trichotillomania: Consensus Among Experts SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; DOUBLE-BLIND; DESCRIPTIVE PSYCHOPATHOLOGY; FUNCTIONAL IMPAIRMENT; HABIT REVERSAL; LONG-TERM; FLUOXETINE; TRIAL; CLOMIPRAMINE; COMORBIDITY C1 [Flessner, Christopher A.] Brown Univ, Warren Alpert Sch Med, Bradley Hasbro Child Res Ctr, Providence, RI 02912 USA. [Penzel, Fred] Western Suffolk Psychol Serv, Huntington, NY USA. [Keuthen, Nancy J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Flessner, CA (reprint author), Rhode Isl Hosp, Dept Child & Adolescent Psychiat, Bradley Hasbro Childrens Res Ctr, 1 Hoppin St,Suite 204, Providence, RI 02903 USA. EM cflessner@lifespan.org RI Citations, TLC SAB/C-4006-2011; Flessner, Christopher/K-1483-2015 NR 32 TC 15 Z9 15 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD AUG PY 2010 VL 17 IS 3 BP 290 EP 300 PG 11 WC Psychology, Clinical SC Psychology GA 615PU UT WOS:000279148000008 ER PT J AU Daughters, SB Magidson, JF Schuster, RM Safren, SA AF Daughters, Stacey B. Magidson, Jessica F. Schuster, Randi M. Safren, Steven A. TI ACT HEALTHY: A Combined Cognitive-Behavioral Depression and Medication Adherence Treatment for HIV-Infected Substance Users SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TREATMENT RETENTION; COCAINE DEPENDENCE; CANCER-PATIENTS; RISK BEHAVIORS; DRUG-ABUSE; VIRAL LOAD; THERAPY; CARE; COMORBIDITY AB The two most common comorbid conditions with HIV are substance use disorders and depression, and individuals with comorbid HIV, depression, and substance dependence face a more chronic and treatment-resistant course. As an example of how to adapt evidence-based approaches to a complex comorbid population, the current case study examined the integration of a combined depression and HIV medication adherence treatment. The resulting intervention, ACT HEALTHY, combines a brief behavioral activation approach specifically developed to treat depression in individuals receiving residential substance abuse treatment (LETS ACT; Daughters et al., 2008) with a brief cognitive-behavioral approach to improving HIV medication adherence (Life-Steps; Safren el al., 1999; Safren et al., 2009). The current case series demonstrates the use of ACT HEALTHY among 3 depressed HIV-positive, low-income African Americans entering residential substance abuse treatment. C1 [Daughters, Stacey B.] Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA. [Safren, Steven A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Daughters, SB (reprint author), Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA. EM daughter@umd.edu FU NIDA NIH HHS [R01 DA022974-01A2, R01 DA022974] NR 58 TC 27 Z9 27 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD AUG PY 2010 VL 17 IS 3 BP 309 EP 321 PG 13 WC Psychology, Clinical SC Psychology GA 615PU UT WOS:000279148000010 PM 21709737 ER PT J AU Perrimon, N Ni, JQ Perkins, L AF Perrimon, Norbert Ni, Jian-Quan Perkins, Lizabeth TI In vivo RNAi: Today and Tomorrow SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; TRANSMEMBRANE PROTEIN SID-1; FUNCTIONAL GENOMIC ANALYSIS; HIGH-THROUGHPUT RNAI; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; C-ELEGANS; GENETIC INTERFERENCE; BACTERIAL-INFECTION; TRANSGENIC RNAI AB RNA interference (RNAi) provides a powerful reverse genetics approach to analyze gene functions both in tissue culture and in vivo. Because of its widespread applicability and effectiveness it has become an essential part of the tool box kits of model organisms such as Caenorhabditis elegans, Drosophila, and the mouse. In addition, the use of RNAi in animals in which genetic tools are either poorly developed or nonexistent enables a myriad of fundamental questions to be asked. Here, we review the methods and applications of in vivo RNAi to characterize gene functions in model organisms and discuss their impact to the study of developmental as well as evolutionary questions. Further, we discuss the applications of RNAi technologies to crop improvement, pest control and RNAi therapeutics, thus providing an appreciation of the potential for phenomenal applications of RNAi to agriculture and medicine. C1 [Perrimon, Norbert; Ni, Jian-Quan] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Perrimon, Norbert; Ni, Jian-Quan] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02175 USA. [Perkins, Lizabeth] Harvard Univ, Sch Med, Pediat Surg Res Labs, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Perrimon, N (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM perrimon@receptor.med.harvard.edu FU HHMI; [GM084947] FX We thank Rui Zhou and Stephanie Mohr for comments on the manuscript and Luping Liu, Donghui Yang-Zhou and Martha Reed assistance on the figures. This work is supported by GM084947 to N.P. and the HHMI. NR 90 TC 80 Z9 85 U1 3 U2 41 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD AUG PY 2010 VL 2 IS 8 AR a003640 DI 10.1101/cshperspect.a003640 PG 11 WC Cell Biology SC Cell Biology GA 634MY UT WOS:000280588200001 PM 20534712 ER PT J AU Storer, NY Zon, LI AF Storer, Narie Y. Zon, Leonard I. TI Zebrafish Models of p53 Functions SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID DEVELOPMENTAL ABNORMALITIES; NEUROFIBROMATOSIS TYPE-1; INSERTIONAL MUTAGENESIS; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; GERMLINE MUTATIONS; SPONTANEOUS TUMORS; BRAF MUTATIONS; HIGH-FREQUENCY; DANIO-RERIO AB Zebrafish models have significantly contributed to our understanding of vertebrate development and, more recently, human disease. The growing number of genetic tools available in zebrafish research has resulted in the identification of many genes involved in developmental and disease processes. In particular, studies in the zebrafish have clarified roles of the p53 tumor suppressor in the formation of specific tumor types, as well as roles of p53 family members during embryonic development. The zebrafish has also been instrumental in identifying novel mechanisms of p53 regulation and highlighting the importance of these mechanisms in vivo. This article will summarize how zebrafish models have been used to reveal numerous, important aspects of p53 function. C1 [Zon, Leonard I.] Harvard Univ, Stem Cell Program, Sch Med, Boston, MA 02115 USA. Harvard Univ, Div Hematol Oncol, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Howard Hughes Med Inst, Sch Med,Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Zon, LI (reprint author), Harvard Univ, Stem Cell Program, Sch Med, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu RI Xie, Huangming/B-2260-2012 FU National Institutes of Health (NIH) [GM07226, 5R01 CA103846-07] FX We thank Craig Ceol and Gessingga Storer for critical reading of this manuscript. N.Y.S. was supported in part by National Institutes of Health (NIH) Cell and Developmental Biology Training Grant GM07226. Cancer research by L.I.Z. is funded by NIH Grant 5R01 CA103846-07. NR 71 TC 23 Z9 23 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD AUG PY 2010 VL 2 IS 8 AR a001123 DI 10.1101/cshperspect.a001123 PG 12 WC Cell Biology SC Cell Biology GA 634MY UT WOS:000280588200005 PM 20679337 ER PT J AU Jakobiec, FA Sandhu, H Bhat, P Colby, K AF Jakobiec, Frederick A. Sandhu, Harpal Bhat, Pooja Colby, Kathryn TI Bilateral Conjunctival Melanocytic Nevi of Simultaneous Onset Simulating Conjunctivitis in a Child SO CORNEA LA English DT Article DE conjunctival nevus; junctional nevus; melanocytic nevus; bilateral nevi; immunohistochemistry ID LESIONS AB A healthy 10-year-old girl developed synchronous, bilateral, temporal redness of the eyes regarded as sectoral conjunctivitis for 5 years that was unresponsive to topical steroids and antihistamines. Finely vascularized, minimally elevated, amelanotic or faintly focally pigmented, epibulbar conjunctival lesions were present bilaterally. The lesions were completely excised. Histopathologic and immunohistochemical evaluations confirmed that they were both predominantly junctional nevi with conspicuous chronic inflammation. Juvenile conjunctival nevi frequently have atypical histopathologic traits that in an adult could be suggestive of melanoma. The differential diagnosis of much less likely disorders includes leukemia, lymphoid tumor (salmon patch), and conjunctival sarcoidosis, among other conditions. The patient has had no recurrence 3 years after surgery. C1 [Jakobiec, Frederick A.; Bhat, Pooja] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Sandhu, Harpal; Bhat, Pooja; Colby, Kathryn] Harvard Univ, Sch Med, Boston, MA USA. [Colby, Kathryn] Massachusetts Eye & Ear Infirm, Cornea Serv, Dept Ophthalmol, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Suite 321,3rd Floor,243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD AUG PY 2010 VL 29 IS 8 BP 937 EP 940 DI 10.1097/ICO.0b013e3181c84480 PG 4 WC Ophthalmology SC Ophthalmology GA 630ED UT WOS:000280254500020 PM 20508514 ER PT J AU Jakobiec, FA Nguyen, J Bhat, P Fay, A AF Jakobiec, Frederick A. Nguyen, John Bhat, Pooja Fay, Aaron TI Recurrent Blue Nevus of the Corneoscleral Limbus SO CORNEA LA English DT Article DE blue nevus; cornea; limbus; recurrent; immunohistochemistry; cryotherapy ID CONJUNCTIVAL MELANOCYTIC LESIONS; MALIGNANT-MELANOMA; CRYOTHERAPY; FEATURES AB Purpose: To describe an unusual corneoscleral blue nevus. Methods: Review of clinical and histopathological characteristics and previous relevant literature supplemented with immunohistochemical studies. Results: A 13-year-old Pakistani girl presented with a 5 X 2-mm, superotemporal, nonmovable, recurrent, black, limbal nodule. The lesion had been incompletely removed two and a half years earlier. Nonfascicular, variably pigmented, banal, spindle melanocytes with bland nuclei were discovered histopathologically in the conjunctival substantia propria and superficial sclera in the original and recurrent specimens. HMB-45+ and MART-1+ immunostainings established that all the variably pigmented spindle cells were melanocytes. Dispersed plump melanophages displayed clumped melanin granules and were shown to have small nuclei after decolorization. The Ki-67 proliferation index was very low (0.05%), supporting a benign diagnosis. No residual pigmentation after excision and cryotherapy was observed in follow-up examinations during a year and a half. Conclusions: Careful histopathological and immunohistochemical evaluation of recurrent, incompletely excised, blue nevi can determine if they remain benign. Adjunctive cryotherapy was performed to prevent further recurrence, based on results from published data. C1 [Jakobiec, Frederick A.] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Eye & Ear Infirm, Oculoplast Serv, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, 243 Charles St,Room 321, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 28 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD AUG PY 2010 VL 29 IS 8 BP 947 EP 951 DI 10.1097/ICO.0b013e3181ca6d1b PG 5 WC Ophthalmology SC Ophthalmology GA 630ED UT WOS:000280254500023 PM 20508501 ER PT J AU Patterson, JE Malani, PN Maragakis, LL AF Patterson, Jan E. Malani, Preeti N. Maragakis, Lisa L. TI Infection control in the intensive care unit: Progress and challenges in systems and accountability SO CRITICAL CARE MEDICINE LA English DT Article ID SAFETY NETWORK AB Attention to the improvement of safety in healthcare lately has focused on healthcare-associated infections, including many that occur in the intensive care unit, such as catheter-related bloodstream infections and ventilator-associated pneumonias. Great strides have been made in decreasing the rates of intensive care unit hospital-acquired infections in the past decade. This is attributable to a number of factors, including standardization of care, technological advances, provider payment reform, and consumer activism. Teamwork and communication remain the most important facets in patient safety. The papers in this supplement examine the roles of human factors and process engineering, survey a spectrum of infection control and safety challenges encountered by critical care practitioners, and assess the future challenges for continued improvement in our systems of care. (Crit Care Med 2010; 38[Suppl.]:S265-S268) C1 [Patterson, Jan E.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Patterson, Jan E.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Malani, Preeti N.] Univ Michigan Hlth Syst, Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Malani, Preeti N.] Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. [Maragakis, Lisa L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Patterson, JE (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM pattersonj@uthscsa.edu FU Basilea; Merck; Pfizer; Schering-Plough FX Dr. Patterson disclosed that her spouse received grant support from Basilea, Merck, Pfizer, and Schering-Plough and is a consultant for Merck, Pfizer, and Basilea. The remaining authors did not disclose any potential conflicts of interest. NR 28 TC 5 Z9 7 U1 0 U2 3 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 AUG PY 2010 VL 38 IS 8 SU S BP S265 EP S268 DI 10.1097/CCM.0b013e3181e69d48 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 628IP UT WOS:000280112100001 PM 20647783 ER PT J AU Flynn, RL Zou, L AF Flynn, Rachel Litman Zou, Lee TI Oligonucleotide/oligosaccharide-binding fold proteins: a growing family of genome guardians SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE OB fold; DNA damage; checkpoint; telomere; DNA repair ID SINGLE-STRANDED-DNA; HOLLIDAY JUNCTION DISSOLVASOME; TOPOISOMERASE-III-ALPHA; OB-FOLD; DAMAGE RESPONSE; HUMAN POT1; A RPA; TELOMERASE PROCESSIVITY; ESSENTIAL COMPONENT; PROTECTS TELOMERES AB The maintenance of genomic stability relies on the coordinated action of a number of cellular processes, including activation of the DNA-damage checkpoint, DNA replication, DNA repair, and telomere homeostasis. Many proteins involved in these cellular processes use different types of functional modules to regulate and execute their functions. Recent studies have revealed that many DNA-damage checkpoint and DNA repair proteins in human cells possess the oligonucleotide/oligosaccharide-binding (OB) fold domains, which are known to bind single-stranded DNA in both prokaryotes and eukaryotes. Furthermore, during the DNA damage response, the OB folds of the human checkpoint and DNA repair proteins play critical roles in DNA binding, protein complex assembly, and regulating protein-protein interactions. These findings suggest that the OB fold is an evolutionarily conserved functional module that is widely used by genome guardians. In this review, we will highlight the functions of several well-characterized or newly discovered eukaryotic OB-fold proteins in the DNA damage response. C1 [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Flynn, Rachel Litman; Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. RP Zou, L (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM zou.lee@mgh.harvard.edu FU NIH [GM076388]; ACS [0902501] FX L.Z. is supported by a NIH grant (GM076388) and is an Ellison New Scholar on Aging. R. L. F. is supported by an ACS fellowship 0902501. NR 93 TC 60 Z9 60 U1 5 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-9238 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PD AUG PY 2010 VL 45 IS 4 BP 266 EP 275 DI 10.3109/10409238.2010.488216 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 636TJ UT WOS:000280763700002 PM 20515430 ER PT J AU Menze, MA Chakraborty, N Clavenna, M Banerjee, M Liu, XH Toner, M Hand, SC AF Menze, Michael A. Chakraborty, Nilay Clavenna, Matthew Banerjee, Mitali Liu, Xiang-Hong Toner, Mehmet Hand, Steven C. TI Metabolic preconditioning of cells with AICAR-riboside: Improved cryopreservation and cell-type specific impacts on energetics and proliferation SO CRYOBIOLOGY LA English DT Article DE AICAR; Adenylate levels; ATP; Metabolism; Cell stasis; Biostabilization ID ACTIVATED PROTEIN-KINASE; KILLIFISH AUSTROFUNDULUS-LIMNAEUS; SANDWICH CONFIGURATION; COLLAGEN SANDWICH; RAT HEPATOCYTES; ENERGY-CHARGE; INHIBITION; DEPRESSION; TOLERANCE; DIAPAUSE AB In species whose evolutionary history has provided natural tolerance to dehydration and freezing, metabolic depression is often a pre-requisite for survival. We tested the hypothesis that preconditioning of mammalian cells with 5-aminoimidazole-4-carboxamide-1-b-o-ribofuranoside (AICAR) to achieve metabolic depression will promote greater survivorship during cryopreservation. AICAR is used extensively to stimulate AMP-activated protein kinase (AMPK), which can result in downregulation of biosynthetic processes. We showed that the metabolic interconversion of AICAR was cell-type dependent. Accumulation of 5-aminoimidazole-4-carboxamide-1b-D-ribofuranosyl-5'-monophosphate (ZMP), as well as other metabolites that possess multiple phosphates (i.e., ZDP, ZTP), varied approximately 3.5-fold across the cell lines tested. AICAR treatment also significantly influenced the concentrations of cellular adenylates (ATP, ADP, and AMP). Depression of cell metabolism and proliferation with AICAR treatment differed among cell lines. Proliferation for a given cell line was negatively correlated with the fold-increase achieved in the 'effective adenylate ratio' ([AMP] + [ZMP])/[ATP]) after AICAR treatment. Metabolic preconditioning with AICAR promoted a significant increase in viability post-freezing in J774.A1 macrophages, HepG2/C3A cells and primary hepatocytes but not in NIH/3T3 fibroblasts or OMK cells. The effect of AICAR on viability after freezing was positively correlated (r(2) = 0.94) with the fold-increase in the 'effective adenylate ratio'. Thus for each cell line, the greater the depression of metabolism and proliferation due to preconditioning with AICAR, the greater was the survivorship post-freezing. (C) 2010 Elsevier Inc. All rights reserved. C1 [Menze, Michael A.; Clavenna, Matthew; Hand, Steven C.] Louisiana State Univ, Dept Biol Sci, Div Cellular Dev & Integrat Biol, Baton Rouge, LA 70803 USA. [Chakraborty, Nilay; Banerjee, Mitali; Liu, Xiang-Hong; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Chakraborty, Nilay; Banerjee, Mitali; Liu, Xiang-Hong; Toner, Mehmet] Shriners Hosp Children, Boston, MA 02114 USA. RP Menze, MA (reprint author), Louisiana State Univ, Dept Biol Sci, Div Cellular Dev & Integrat Biol, 202 Life Sci Bldg, Baton Rouge, LA 70803 USA. EM menze@lsu.edu RI Chakraborty, Nilay/C-3118-2009; OI Menze, Michael/0000-0003-1072-5462 FU National Institutes of Health [2-RO1-DK046270-14A1] FX This study was supported by National Institutes of Health Grant 2-RO1-DK046270-14A1. NR 45 TC 14 Z9 14 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD AUG PY 2010 VL 61 IS 1 BP 79 EP 88 DI 10.1016/j.cryobiol.2010.05.004 PG 10 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 640SY UT WOS:000281073900013 PM 20510224 ER PT J AU BuAbbud, JC Al-latayfeh, MM Sun, JK AF BuAbbud, John C. Al-latayfeh, Motasem M. Sun, Jennifer K. TI Optical Coherence Tomography Imaging for Diabetic Retinopathy and Macular Edema SO CURRENT DIABETES REPORTS LA English DT Article DE Diabetic retinopathy; Diabetic macular edema; Optical coherence tomography; OCT; Spectral domain; Time domain ID RETINAL THICKNESS; FUNDUS PHOTOGRAPHY; VISUAL-ACUITY; TIME-DOMAIN; EYES; BIOMICROSCOPY; PATTERNS; SPEED; OCT AB Optical coherence tomography (OCT) is a noninvasive imaging modality that uses low-coherent interferometry to visualize an optical cross-section of biological tissues. Over the past two decades, the ability to perform OCT imaging of the neural retina has afforded clinicians and researchers a highly reproducible method of diagnosing and following diabetic macular edema (DME) that compares favorably to other methods of DME assessment such as clinical examination and fundus photography. Although central subfield mean thickness has been the OCT parameter most commonly used to evaluate DME in clinical research trials, OCT also allows evaluation of morphologic changes that occur in DME, including compact retinal thickening, intraretinal cystic changes, subretinal fluid, and vitreomacular traction. OCT parameters have been shown to be only moderately correlated with visual acuity. However, improvements in technology leading to higher resolution, faster acquisition speed, image registration, and three-dimensional imaging that are available with newer spectral domain OCT models may allow future identification of valid OCT-derived surrogate markers for visual function in patients with diabetes. C1 [BuAbbud, John C.; Al-latayfeh, Motasem M.; Sun, Jennifer K.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [BuAbbud, John C.; Al-latayfeh, Motasem M.] Joslin Diabet Ctr, Eye Res Sect, Boston, MA 02215 USA. [Sun, Jennifer K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. RP Sun, JK (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM Jennifer.sun@joslin.harvard.edu NR 32 TC 11 Z9 13 U1 0 U2 4 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD AUG PY 2010 VL 10 IS 4 BP 264 EP 269 DI 10.1007/s11892-010-0129-z PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 615IT UT WOS:000279128900002 PM 20556548 ER PT J AU Feener, EP AF Feener, Edward P. TI Plasma Kallikrein and Diabetic Macular Edema SO CURRENT DIABETES REPORTS LA English DT Article DE Diabetic macular edema; Diabetic retinopathy; Plasma kallikrein; Kallikrein kinin system; Bradykinin; Diabetes; Inflammation; Vascular permeability; Vitreous fluid; Retina; Proteomics; Complement 1 inhibitor; Angioedema ID RETINAL VASCULAR-PERMEABILITY; HUMAN OCULAR-TISSUES; KININ B-1 RECEPTORS; FACTOR-XII; RETINOPATHY; BRADYKININ; ACTIVATION; RATS; PREKALLIKREIN; SYSTEM AB Recent proteomic studies have identified components of the kallikrein kinin system, including plasma kallikrein, factor XII, and kininogen, in vitreous obtained from individuals with advanced diabetic retinopathy. In rodent models, activation of plasma kallikrein in vitreous increases retinal vascular permeability; whereas inhibition of the kallikrein kinin system reduces retinal leakage induced by diabetes and hypertension. These findings suggest that intraocular activation of the plasma kallikrein pathway may contribute to excessive retinal vascular permeability that can lead to diabetic macular edema. The kallikrein kinin system contains two separate and independently regulated serine proteases that generate bradykinin peptides: plasma kallikrein and tissue kallikrein. Tissue kallikrein is expressed in the retina and ciliary body, where it has been implicated in exerting autocrine or paracrine effects via bradykinin receptors that are colocalized in these tissues. Emerging evidence suggests that plasma kallikrein inhibitors may provide a new therapeutic opportunity to reduce retinal vascular permeability. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, Boston, MA 02215 USA. RP Feener, EP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM Edward.Feener@joslin.harvard.edu FU US National Institutes of Health [EY019029, DK 36836]; Juvenile Diabetes Research Foundation FX This work was supported in part by the US National Institutes of Health (grants EY019029, DK 36836) and the Juvenile Diabetes Research Foundation. NR 47 TC 16 Z9 16 U1 0 U2 4 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD AUG PY 2010 VL 10 IS 4 BP 270 EP 275 DI 10.1007/s11892-010-0127-1 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 615IT UT WOS:000279128900003 PM 20535647 ER PT J AU Rothenberg, SM Settleman, J AF Rothenberg, S. Michael Settleman, Jeff TI Discovering Tumor Suppressor Genes Through Genome-Wide Copy Number Analysis SO CURRENT GENOMICS LA English DT Article DE Array CGH; copy number analysis; cancer; tumor suppressor genes ID ARRAY-CGH DATA; RECESSIVE JUVENILE PARKINSONISM; NUCLEOTIDE POLYMORPHISM ARRAYS; ACUTE LYMPHOBLASTIC-LEUKEMIA; METASTATIC BREAST-CANCER; HOMOZYGOUS DELETIONS; WILMS-TUMOR; LUNG-CANCER; OLIGONUCLEOTIDE ARRAYS; PANCREATIC-CARCINOMA AB Classical tumor suppressor gene discovery has largely involved linkage analysis and loss-of-heterozygosity (LOH) screens, followed by detailed mapping of relatively large chromosomal regions. Subsequent efforts made use of genome-wide PCR-based methods to detect rare homozygous deletions. More recently, high-resolution genomic arrays have been applied to cancer gene discovery. However, accurate characterization of regions of genomic loss is particularly challenging due to sample heterogeneity, the small size of deleted regions and the high frequency of germline copy number polymorphisms. Here, we review the application of genome-wide copy number analysis to the specific problem of identifying tumor suppressor genes. C1 [Settleman, Jeff] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Settleman, Jeff] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu FU MGH Tosteson Postdoctoral Fellowship FX The authors wish to thank Miguel N. Rivera for critical reading of the manuscript. S. M. Rothenberg is supported by the MGH Tosteson Postdoctoral Fellowship. NR 85 TC 9 Z9 9 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 1389-2029 J9 CURR GENOMICS JI Curr. Genomics PD AUG PY 2010 VL 11 IS 5 BP 297 EP 310 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 632XV UT WOS:000280463800001 PM 21286308 ER PT J AU Jung, HJ Yang, MZ Kwon, KH Yenari, MA Choi, YJ Lee, WT Park, KA Lee, JE AF Jung, Hyun Joo Yang, Mei Zi Kwon, Ki Hyo Yenari, Midori A. Choi, Yoon Jung Lee, Won Taek Park, Kyung Ah Lee, Jong Eun TI Endogenous Agmatine Inhibits Cerebral Vascular Matrix Metalloproteinases Expression by Regulating Activating Transcription Factor 3 and Endothelial Nitric Oxide Synthesis SO CURRENT NEUROVASCULAR RESEARCH LA English DT Article DE Arginine decarboxylase; agmatine; activating transcription factor 3; endothelial cell; matrix metalloproteinases; endothelial nitric oxide synthase ID BLOOD-BRAIN-BARRIER; ALPHA-INDUCED APOPTOSIS; RETINAL GANGLION-CELLS; RAT-BRAIN; TISSUE INHIBITORS; ATF3 EXPRESSION; MULTIPLE ROLES; C-JUN; ISCHEMIA; MATRIX-METALLOPROTEINASE-9 AB Earlier investigations from our laboratory demonstrated that the expression of matrix metalloproteinases (MMPs) was down-regulated by exogenously administered agmatine against ischemia-like injuries in the murine brain capillary endothelial (bEnd.3) cells. In our present study, we intended to investigate the mechanism involved in the inhibition of MMPs in bEnd.3 cells infected with retroviral containing human arginine decarboxylase (hADC) gene which can synthesize agmatine endogenously (ADC Delta bEnd.3 cells). The ADC Delta bEnd.3 cells were subjected to oxygen glucose deprivation (OGD, 6 hrs) with reperfusion (18 hrs). High performance liquid chromatography (HPLC) analysis revealed the high levels of agmatine in the ADC Delta bEnd.3 cells compared to other experimental groups. The results demonstrated significant decrease in cell death and increase in the nitric oxide (NO) production in the ADC Delta bEnd.3 cells. The increased expression of MMP-2 and MMP-9, and decreased expression of endothelial nitric oxide synthase (eNOS) by ischemic injury was attenuated in ADC Delta bEnd.3 cells. Moreover, the expression of activating transcription factor 3 (ATF3) was increased significantly in ADC Delta bEnd.3 cells. In addition, the suppression of the MMP-2 and MMP-9 expression in ADC Delta bEnd.3 cells was prevented with ATF3 small interfering RNA (siRNA) treatment. These results suggest that the endogenous agmatine in ADC Delta bEnd.3 cells inhibits the MMPs expression mediated via the regulation of eNOS, NO and ATF3. C1 [Jung, Hyun Joo; Kwon, Ki Hyo; Choi, Yoon Jung; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun] Yonsei Univ, Coll Med, Dept Anat, Seoul 120752, South Korea. [Jung, Hyun Joo; Yang, Mei Zi; Lee, Jong Eun] Yonsei Univ, Coll Med, BK Project Med Sci 21, Seoul 120752, South Korea. [Yang, Mei Zi] Binzhou Med Univ, Yantai 264003, Peoples R China. [Yenari, Midori A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Lee, JE (reprint author), Yonsei Univ, Coll Med, Dept Anat, 134 Shinchon Dong, Seoul 120752, South Korea. EM jelee@yumc.yonsei.ac.kr OI Lee, Jong Eun/0000-0001-6203-7413 FU Korea government (MEST) [2009-0052626] FX This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. 2009-0052626). NR 60 TC 13 Z9 13 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2026 J9 CURR NEUROVASC RES JI Curr. Neurovasc. Res. PD AUG PY 2010 VL 7 IS 3 BP 201 EP 212 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 633MG UT WOS:000280506500004 PM 20560878 ER PT J AU Beerman, I Maloney, WJ Weissmann, IL Rossi, DJ AF Beerman, Isabel Maloney, William J. Weissmann, Irving L. Rossi, Derrick J. TI Stem cells and the aging hematopoietic system SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID AGE-RELATED-CHANGES; MYELODYSPLASTIC SYNDROMES; DISEASE PROGRESSION; BONE-MARROW; DNA-REPAIR; DIFFERENTIATION; GENE; TRANSPLANTATION; METHYLATION; MECHANISM AB Advancing age is accompanied by a number of clinically significant conditions arising in the hematopoietic system that include: diminution and decreased competence of the adaptive immune system, elevated incidence of certain autoimmune diseases, increased hematological malignancies, and elevated incidence of age-associated anemia. As with most tissues, the aged hematopoietic system also exhibits a reduced capacity to regenerate and return to normal homeostasis after injury or stress. Evidence suggests age-dependent functional alterations within the hematopoietic stem cell compartment significantly contribute to many of these pathophysiologies. Recent developments have shed light on how aging of the hematopoietic stem cell compartment contributes to hematopoietic decline through diverse mechanisms. C1 [Beerman, Isabel; Rossi, Derrick J.] Harvard Univ, Dept Pathol,Childrens Hosp Boston, Harvard Stem Cell Inst, Immune Dis Inst,Program Cellular & Mol Med, Boston, MA 02115 USA. [Maloney, William J.] Stanford Univ, Orthopaed Res Labs, Dept Orthopaed Surg, Sch Med, Stanford, CA 94305 USA. [Weissmann, Irving L.] Stanford Univ, Stanford Inst Stem Cell Biol & Regenerat Med, Ctr Canc, Stanford, CA 94305 USA. [Weissmann, Irving L.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. RP Beerman, I (reprint author), Harvard Univ, Dept Pathol,Childrens Hosp Boston, Harvard Stem Cell Inst, Immune Dis Inst,Program Cellular & Mol Med, 200 Longwood Ave,Warren Alpert Bldg,Room 253, Boston, MA 02115 USA. EM beerman@idi.harvard.edu NR 50 TC 68 Z9 71 U1 0 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2010 VL 22 IS 4 BP 500 EP 506 DI 10.1016/j.coi.2010.06.007 PG 7 WC Immunology SC Immunology GA 645MH UT WOS:000281462800013 PM 20650622 ER PT J AU Chung, RJ Burke, PJ Goodman, E AF Chung, Richard J. Burke, Pamela J. Goodman, Elizabeth TI Firm foundations: strength-based approaches to adolescent chronic disease SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE adolescents; chronic disease; motivational interviewing; strength-based approach ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE SETTINGS; YOUTH DEVELOPMENT; MOTIVATIONAL-INTERVENTION; PHYSICAL-ACTIVITY; RISK; PREVENTION; OUTCOMES; PROGRAM; OBESITY AB Purpose of review Chronic disease management is an increasingly important aspect of caring for adolescents. Strength-based approaches hold tremendous promise in the face of current challenges. Recent clinical innovations and research findings that provide evidence of the efficacy of strength-based approaches and represent a fundamental evolution in the clinical approach to adolescent care are reviewed. Recent findings Resilience and positive youth development are important conceptual frameworks in adolescent health, which have recently been brought into the clinic setting in the form of the strength-based approach to care. In parallel, studies of motivational interviewing, a strength-based technique with known efficacy in behavioral change, have begun to demonstrate clinical efficacy in various adolescent chronic disease applications. The coupling of a strength-based approach with motivational interviewing holds promise for not only modifying end behaviors but also helping teens to develop strengths and assets to promote general well-being and healthy development. This distinction in goals might be described as the difference between being transiently problem-free and durably problem-resistant. Summary Strength-based approaches, including motivational interviewing, hold tremendous potential for equipping providers to address the rapidly increasing burden of chronic disease in adolescents. C1 [Chung, Richard J.; Burke, Pamela J.] Harvard Univ, Div Adolescent Young Adult Med, Childrens Hosp Boston, Sch Med,Dept Med, Boston, MA 02115 USA. [Goodman, Elizabeth] MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. RP Chung, RJ (reprint author), Harvard Univ, Div Adolescent Young Adult Med, Childrens Hosp Boston, Sch Med,Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM richard.chung@childrens.harvard.edu OI Goodman, Elizabeth/0000-0002-9640-9884 FU Maternal and Child Health Bureau, Health Resources and Services Administration [T71MC00009] FX Supported in part by the Leadership Education in Adolescent Health Training grant no. T71MC00009 from the Maternal and Child Health Bureau, Health Resources and Services Administration. NR 52 TC 8 Z9 8 U1 1 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD AUG PY 2010 VL 22 IS 4 BP 389 EP 397 DI 10.1097/MOP.0b013e32833a468e PG 9 WC Pediatrics SC Pediatrics GA 625QW UT WOS:000279911100002 PM 20489640 ER PT J AU Borus, JS Laffel, L AF Borus, Joshua S. Laffel, Lori TI Adherence challenges in the management of type 1 diabetes in adolescents: prevention and intervention SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE adherence; adolescent; motivational interviewing; type 1 diabetes ID RANDOMIZED CONTROLLED-TRIAL; POOR GLYCEMIC CONTROL; SELF-CARE; SOCIAL SUPPORT; BLOOD-GLUCOSE; MEDICATION ADHERENCE; DEPRESSIVE SYMPTOMS; INTENSIVE TREATMENT; METABOLIC-CONTROL; NATURAL-HISTORY AB Purpose of review Despite the availability of effective therapies, adolescents with type 1 diabetes demonstrate poorer adherence to treatment regimens compared with other pediatric age groups. Nonadherence is tightly linked to suboptimal glycemic control, increasing morbidity, and risk for premature mortality. This article will review barriers to adherence and discuss interventions that have shown promise in improving outcomes for this population. Recent findings Adolescents face numerous obstacles to adherence, including developmental behaviors, flux in family dynamics, and perceived social pressures, which compound the relative insulin resistance brought on by pubertal physiology. Some successful interventions have relied on encouraging nonjudgmental family support in the daily tasks of blood glucose monitoring and insulin administration. Other interventions overcome these barriers through the use of motivational interviewing and problem-solving techniques, flexibility in dietary recommendations, and extending provider outreach and support with technology. Summary Effective interventions build on teens' internal and external supports (family, technology, and internal motivation) in order to simplify their management of diabetes and provide opportunities for the teens to share the burdens of care. Although such strategies help to minimize the demands placed upon teens with diabetes, suboptimal glycemic control will likely persist for the majority of adolescents until technological breakthroughs allow for automated insulin delivery in closed loop systems. C1 [Borus, Joshua S.] Harvard Univ, Sch Med, Div Adolescent Young Adult Med, Childrens Hosp Boston,Dept Med, Boston, MA 02115 USA. [Laffel, Lori] Harvard Univ, Sch Med, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect,Joslin Diabet Ctr, Boston, MA 02115 USA. RP Borus, JS (reprint author), Harvard Univ, Sch Med, Div Adolescent Young Adult Med, Childrens Hosp Boston,Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. EM joshua.borus@childrens.harvard.edu RI Hanghoj, Signe/E-2440-2012 FU Maternal and Child Health Bureau, Health Resources and Services Administration [T71MC00009]; National Institute of Diabetes, Digestive and Kidney Diseases [K12 DK6369605, P30DK036836]; Charles H. Hood Foundation; Maria Griffin Drury Pediatric Fund; Katherine Adler Astrove Youth Education Fund FX Supported in part by the Leadership Education in Adolescent Health training grant no. T71MC00009 from the Maternal and Child Health Bureau, Health Resources and Services Administration. Other supports, K12 DK6369605 and P30DK036836, were from the National Institute of Diabetes, Digestive and Kidney Diseases; the Charles H. Hood Foundation; the Maria Griffin Drury Pediatric Fund; and the Katherine Adler Astrove Youth Education Fund. NR 52 TC 53 Z9 54 U1 7 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 EI 1531-698X J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD AUG PY 2010 VL 22 IS 4 BP 405 EP 411 DI 10.1097/MOP.0b013e32833a46a7 PG 7 WC Pediatrics SC Pediatrics GA 625QW UT WOS:000279911100004 PM 20489639 ER PT J AU Cypess, AM Kahn, CR AF Cypess, Aaron M. Kahn, C. Ronald TI The role and importance of brown adipose tissue in energy homeostasis SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE brown adipose tissue; energy balance; PET-computed tomography; uncoupling protein 1 ID MITOCHONDRIAL UNCOUPLING PROTEIN; INDUCED THERMOGENESIS; ADULT HUMANS; BETA(3)-ADRENOCEPTOR AGONIST; NONSHIVERING THERMOGENESIS; F-18-FDG PET/CT; WHITE FAT; COLD; OBESITY; ADIPOCYTES AB Purpose of review Children and adults have two major types of adipocytes, which represent the predominant cells in white adipose tissue, which is involved in energy storage, and brown adipose tissue (BAT), which is responsible for thermogenesis and energy expenditure. This review discusses BAT physiology and evaluates the recent discoveries regarding its development, identification, and function. Recent findings Last year, multiple independent research teams using combined PET and computed tomography imaging, immunohistochemistry, and gene and protein expression have proven conclusively that adult humans have functional BAT. In parallel, basic studies defined BAT origins, its transcriptional regulation, and the role of hormones in BAT growth and activation. These methods have begun to be applied to children to understand pediatric BAT anatomy and physiology. Summary Adult humans have functional BAT, which plays a role in energy balance. BAT is more prevalent in children, suggesting an even greater physiological role than that seen in adults. Future studies will identify safe ways to quantify BAT mass and activity and which interventions might be used to increase BAT mass, thermogenesis, or both to treat obesity. C1 [Cypess, Aaron M.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU Eli Lilly Foundation; National Institutes of Health (NIH) [DK082659, DK046200, DK081604, DK087317, RR025757]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [P30 DK036836] FX This work was supported in part by the Eli Lilly Foundation and National Institutes of Health (NIH) grant numbers DK082659 (to C.R.K.), DK046200, DK081604, DK087317, RR025757 (to A.M.C.), and P30 DK036836 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National NIDDK or the NIH. NR 65 TC 25 Z9 28 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD AUG PY 2010 VL 22 IS 4 BP 478 EP 484 DI 10.1097/MOP.0b013e32833a8d6e PG 7 WC Pediatrics SC Pediatrics GA 625QW UT WOS:000279911100015 PM 20489634 ER PT J AU Tseng, KAS Beane, WS Lemire, JM Masi, A Levin, M AF Tseng, Kelly Ai-Sun Beane, Wendy S. Lemire, Joan M. Masi, Alessio Levin, Michael TI Na-v-mediated sodium transport is required for vertebrate appendage regeneration SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 69th Annual Meeting of the Society-for-Developmental-Biology/Japanese-Society-of-Developmental-Biol ogists CY AUG 05-09, 2010 CL Albuquerque, NM SP Soc Dev Biol, Japanese Soc Dev Biologists C1 [Tseng, Kelly Ai-Sun; Beane, Wendy S.; Lemire, Joan M.; Levin, Michael] Tufts Univ, Ctr Reg & Dev Biol, Medford, MA 02155 USA. [Masi, Alessio; Levin, Michael] Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2010 VL 344 IS 1 MA 369 BP 519 EP 519 DI 10.1016/j.ydbio.2010.05.376 PG 1 WC Developmental Biology SC Developmental Biology GA 632LO UT WOS:000280426400393 ER PT J AU Horton, ES Silberman, C Davis, KL Berria, R AF Horton, Edward S. Silberman, Cheryl Davis, Keith L. Berria, Rachele TI Weight Loss, Glycemic Control, and Changes in Cardiovascular Biomarkers in Patients With Type 2 Diabetes Receiving Incretin Therapies or Insulin in a Large Cohort Database SO DIABETES CARE LA English DT Article ID DIPEPTIDYL PEPTIDASE-4 INHIBITOR; DISEASE RISK-FACTORS; EXENATIDE TREATMENT; HEPATIC BIOMARKERS; INTERIM ANALYSIS; OBESITY; METFORMIN; INDIVIDUALS; SITAGLIPTIN; PREVENTION AB OBJECTIVE Weight loss in patients with type 2 diabetes can improve glycemic control, lower blood pressure, and improve dyslipidemia. Glucagon-like peptide (GLP-1) receptor agonists are associated with weight loss and have potentially beneficial effects on cardiovascular risk biomarkers; however, there is limited information to indicate whether these effects remain outside of clinical trials. RESEARCH DESIGN AND METHODS Medical records from the General Electric Centricity research database were analyzed retrospectively to evaluate the relationship between weight loss and glycemic control and changes in blood pressure and lipids in patients with type 2 diabetes initiating therapy with exenatide, sitagliptin, or insulin. Baseline and follow-up (90-365 days after the index date) for weight, A1C, fasting blood glucose (FBG), blood pressure, triglycerides, and LDL, HDL, and total cholesterol were assessed. RESULTS A total of 6,280, 5,861, and 32,398 patients receiving exenatide, sitagliptin, or insulin, respectively, were included in the analysis. Exenatide-treated patients lost a mean SD of 3.0 +/- 7.33 kg, sitagliptin-treated patients lost 1.1 +/- 5.39 kg, and insulin-treated patients gained 0.6 +/- 9.49 kg. There was a significant association between weight loss and a reduction in A1C and FBG with exenatide only and a reduction in blood pressure for all therapies. Weight loss was associated with some improvements in lipids, primarily in the GLP-1 receptor agonist group, with little association in the insulin group. CONCLUSIONS Weight reduction with GLP-1 receptor agonists was associated with a shift toward a more favorable cardiovascular risk profile. Outcome trials are needed to determine whether improvement in biomarkers translates into a reduction in cardiovascular events in patients with type 2 diabetes. C1 [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Silberman, Cheryl; Berria, Rachele] Roche Labs, Nutley, NJ USA. [Davis, Keith L.] RTI Hlth Solut, Res Triangle Pk, NC USA. RP Horton, ES (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM edward.horton@joslin.harvard.edu FU Roche; Amylin; Eli Lilly FX This research was supported by Roche. Editorial assistance was provided by Susan Sutch, PharmD, of Evidence Scientific Solutions, which was funded by Roche.; E.S.H. has research grants from Amylin and Eli Lilly and serves on advisory boards or is a consultant for Abbott, AstraZeneca, Bristol Myers-Squibb, Daiichi-Sankyo, Medtronic, Merck, Metabasis, Novartis, Roche, Sanofi-Aventis, Takeda, and Tethys. C.S. is an employee and R.B. was an employee of Roche Laboratories at the time of the research and writing of the manuscript, which is developing a GLP-1 receptor agonist. K.L.D. is an employee of RTI, which was paid by Roche to conduct this research. No other potential conflicts of interest to this study were reported. NR 21 TC 75 Z9 84 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2010 VL 33 IS 8 BP 1759 EP 1765 DI 10.2337/dc09-2062 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 645AF UT WOS:000281422600014 PM 20460445 ER PT J AU Borg, R Kuenen, JC Carstensen, B Zheng, H Nathan, DM Heine, RJ Nerup, J Borch-Johnsen, K Witte, DR AF Borg, R. Kuenen, J. C. Carstensen, B. Zheng, H. Nathan, D. M. Heine, R. J. Nerup, J. Borch-Johnsen, K. Witte, D. R. CA ADAG Study Grp TI Real-life glycaemic profiles in non-diabetic individuals with low fasting glucose and normal HbA(1c): the A1C-Derived Average Glucose (ADAG) study SO DIABETOLOGIA LA English DT Article DE Continuous glucose monitoring; Glucose monitoring; Glycaemia in healthy individuals; Non-diabetic glucose exposure; Normoglycaemia ID TOLERANCE AB Real-life glycaemic profiles of healthy individuals are poorly studied. Our aim was to analyse to what extent individuals without diabetes exceed OGTT thresholds for impaired glucose tolerance (IGT) and diabetes. In the A1C-Derived Average Glucose (ADAG) study, 80 participants without diabetes completed an intensive glucose monitoring period of 12 weeks. From these data, we calculated the average 24 h glucose exposure as time spent above different plasma glucose thresholds. We also derived indices of postprandial glucose levels, glucose variability and HbA(1c). We found that 93% of participants reached glucose concentrations above the IGT threshold of 7.8 mmol/l and spent a median of 26 min/day above this level during continuous glucose monitoring. Eight individuals (10%) spent more than 2 h in the IGT range. They had higher HbA(1c), fasting plasma glucose (FPG), age and BMI than those who did not. Seven participants (9%) reached glucose concentrations above 11.1 mmol/l during monitoring. Even though the non-diabetic individuals monitored in the ADAG study were selected on the basis of a very low level of baseline FPG, 10% of these spent a considerable amount of time at glucose levels considered to be 'prediabetic' or indicating IGT. This highlights the fact that exposure to moderately elevated glucose levels remains under-appreciated when individuals are classified on the basis of isolated glucose measurements. C1 [Borg, R.; Carstensen, B.; Nerup, J.; Borch-Johnsen, K.; Witte, D. R.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Kuenen, J. C.; Heine, R. J.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Heine, R. J.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Zheng, H.; Nathan, D. M.] Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. [Zheng, H.; Nathan, D. M.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Zheng, H.; Nathan, D. M.] Harvard Univ, Sch Med, Boston, MA USA. RP Borg, R (reprint author), Steno Diabet Ctr, Niels Steensens Vej 2-4, DK-2820 Gentofte, Denmark. EM RBrg@steno.dk RI Witte, Daniel/C-1722-2008 OI Witte, Daniel/0000-0002-0769-2922 FU American Diabetes Association; European Association; Abbott Diabetes Care; Bayer Healthcare; GlaxoSmithKline; sanofi-aventis Netherlands; Merck; Lifescan; Medtronic Minimed; Sehested Hansen Foundation; Clinical Development Foundation at Steno Diabetes Center; Danish Diabetes Association FX The ADAG study was supported by research grants from the American Diabetes Association and the European Association for the Study of Diabetes. Financial support was also provided by Abbott Diabetes Care, Bayer Healthcare, GlaxoSmithKline, sanofi-aventis Netherlands, Merck, Lifescan and Medtronic Minimed. Supplies and equipment were provided by Medtronic Minimed, Lifescan and HemoCue.; The Steno substudy was supported by research grants from the Sehested Hansen Foundation, the Clinical Development Foundation at Steno Diabetes Center and the Danish Diabetes Association. NR 6 TC 15 Z9 20 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 AUG PY 2010 VL 53 IS 8 BP 1608 EP 1611 DI 10.1007/s00125-010-1741-9 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 616FG UT WOS:000279193800011 PM 20396998 ER PT J AU Gianani, R Campbell-Thompson, M Sarkar, SA Wasserfall, C Pugliese, A Solis, JM Kent, SC Hering, BJ West, E Steck, A Bonner-Weir, S Atkinson, MA Coppieters, K von Herrath, M Eisenbarth, GS AF Gianani, R. Campbell-Thompson, M. Sarkar, S. A. Wasserfall, C. Pugliese, A. Solis, J. M. Kent, S. C. Hering, B. J. West, E. Steck, A. Bonner-Weir, S. Atkinson, M. A. Coppieters, K. von Herrath, M. Eisenbarth, G. S. TI Dimorphic histopathology of long-standing childhood-onset diabetes (vol 53, pg 690, 2010) SO DIABETOLOGIA LA English DT Correction C1 [Gianani, R.; Sarkar, S. A.; Solis, J. M.; West, E.; Steck, A.; Eisenbarth, G. S.] Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, Aurora, CO 80055 USA. [Campbell-Thompson, M.; Wasserfall, C.; Atkinson, M. A.] Univ Florida, Dept Pathol, Gainesville, FL 32611 USA. [Pugliese, A.] Diabet Res Inst, Miami, FL USA. [Kent, S. C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. [Hering, B. J.] Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN USA. [Bonner-Weir, S.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Coppieters, K.; von Herrath, M.] La Jolla Inst Allergol & Immunol, La Jolla, CA USA. RP Gianani, R (reprint author), Univ Colorado Denver, Barbara Davis Ctr Childhood Diabet, 1775 Aurora Court, Aurora, CO 80055 USA. EM roberto.gianani@ucdenver.edu RI wasserfall, clive/J-9078-2012 OI wasserfall, clive/0000-0002-3522-8932 NR 1 TC 1 Z9 1 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 AUG PY 2010 VL 53 IS 8 BP 1811 EP 1812 DI 10.1007/s00125-010-1769-x PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 616FG UT WOS:000279193800035 ER PT J AU Markland, AD Greer, WJ Vogt, A Redden, DT Goode, PS Burgio, KL Richter, HE AF Markland, Alayne D. Greer, W. Jerod Vogt, Alicia Redden, David T. Goode, Patricia S. Burgio, Kathryn L. Richter, Holly E. TI Factors Impacting Quality of Life in Women With Fecal Incontinence SO DISEASES OF THE COLON & RECTUM LA English DT Article DE Bowel symptoms; Fecal incontinence; Quality of life; Urinary incontinence; Women ID URINARY-INCONTINENCE; ANAL INCONTINENCE; SEVERITY INDEX; RISK-FACTORS; PREVALENCE; COMMUNITY; ADULTS; OLDER; SYMPTOMS; RELIABILITY AB PURPOSE: The aim of this study was to characterize differences in health-related quality of life among women presenting for treatment of fecal incontinence. METHODS: Among 155 women presenting for treatment of fecal incontinence in a specialty clinic, validated questionnaires measured impact on quality of life (Modified Manchester Health Questionnaire) and severity (the Fecal Incontinence Severity Index). Bowel symptoms, including frequency, urgency, and stool consistency, were ascertained. Comorbid diseases were self-reported. Linear regression models were constructed from significant univariate variables to examine differences observed in quality of life scores. RESULTS: The average age was 58.7 +/- 11.5 years, with no differences found in quality of life scores according to race, body mass index, or number of vaginal deliveries (P > .05). Younger age, increased urinary incontinence symptoms, prior cholecystectomy, prior hysterectomy, and severity of bowel symptoms correlated with a negative impact on quality of life in univariate analysis (P < .05). Average severity scores were 30.5 +/- 13.7, with moderate correlation seen with increasing severity and quality of life scores (R(2) = 0.60). After controlling for severity, women had increased quality of life scores with more bowel urgency (15 points; 95% CI, 8.1-21.2), harder stool consistency (10 points; 95% CI, 3.8-16.3), and prior hysterectomy (9 points; 95% CI, 2.7-15.4). CONCLUSION: Bowel symptoms and having undergone a hysterectomy had the greatest negative impact on quality of life in women seeking treatment for fecal incontinence. Targeting individualized treatments to improve bowel symptoms may improve quality of life for women with fecal incontinence. C1 [Markland, Alayne D.; Redden, David T.; Goode, Patricia S.; Burgio, Kathryn L.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs Med Ctr, Birmingham, AL USA. [Markland, Alayne D.; Goode, Patricia S.; Burgio, Kathryn L.] Univ Alabama, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [Greer, W. Jerod; Vogt, Alicia; Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Div Womens Pelv Med & Reconstruct Surg, Birmingham, AL 35294 USA. [Redden, David T.] Univ Alabama, Birmingham Sch Publ Hlth, Birmingham, AL USA. RP Markland, AD (reprint author), Birmingham VA Med Ctr, GRECC 11G, 700 19th St S, Birmingham, AL 35233 USA. EM amarkland@aging.uab.edu OI Markland, Alayne/0000-0002-6567-6744 FU National Institutes of Health [K24DK068389-03]; Veterans Health Administration [CDA-2]; Hartford/Southeast Center of Excellence in Geriatric Medicine FX This work was supported by National Institutes of Health grant K24DK068389-03 to Dr Richter; Veterans Health Administration Career Development Award (CDA-2) to Dr Markland; and a Hartford/Southeast Center of Excellence in Geriatric Medicine Grant to Dr Markland. NR 27 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD AUG PY 2010 VL 53 IS 8 BP 1148 EP 1154 DI 10.1007/DCR.0b013e3181d5da6c PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 625DF UT WOS:000279872600009 PM 20628278 ER PT J AU Hayeck, TJ Kong, CY Spechler, SJ Gazelle, GS Hur, C AF Hayeck, T. J. Kong, C. Y. Spechler, S. J. Gazelle, G. S. Hur, C. TI The prevalence of Barrett's esophagus in the US: estimates from a simulation model confirmed by SEER data SO DISEASES OF THE ESOPHAGUS LA English DT Article DE adenocarcinoma; Barrett's esophagus; computer models; computer simulation; esophageal cancer; SEER program ID GASTROESOPHAGEAL-REFLUX DISEASE; CLINICAL SPECTRUM; GASTRIC CARDIA; ADENOCARCINOMA; POPULATION; RISK; SYMPTOMS; CANCER; SURVEILLANCE; TRENDS AB P>Barrett's esophagus (BE) is the precursor and the biggest risk factor for esophageal adenocarcinoma (EAC), the solid cancer with the fastest rising incidence in the US and western world. Current strategies to decrease morbidity and mortality from EAC have focused on identifying and surveying patients with BE using upper endoscopy. An accurate estimate of the number of patients with BE in the population is important to inform public health policy and to prioritize resources for potential screening and management programs. However, the true prevalence of BE is difficult to ascertain because the condition frequently is symptomatically silent, and the numerous clinical studies that have analyzed BE prevalence have produced a wide range of estimates. The aim of this study was to use a computer simulation disease model of EAC to determine the estimates for BE prevalence that best align with US Surveillance Epidemiology and End Results (SEER) cancer registry data. A previously developed mathematical model of EAC was modified to perform this analysis. The model consists of six health states: normal, gastroesophageal reflux disease (GERD), BE, undetected cancer, detected cancer, and death. Published literature regarding the transition rates between these states were used to provide boundaries. During the one million computer simulations that were performed, these transition rates were systematically varied, producing differing prevalences for the numerous health states. Two filters were sequentially applied to select out superior simulations that were most consistent with clinical data. First, among these million simulations, the 1000 that best reproduced SEER cancer incidence data were selected. Next, of those 1000 best simulations, the 100 with an overall calculated BE to Detected Cancer rates closest to published estimates were selected. Finally, the prevalence of BE in the final set of best 100 simulations was analyzed. We present histogram data depicting BE prevalences for all one million simulations, the 1000 simulations that best approximate SEER data, and the final set of 100 simulations. Using the best 100 simulations, we estimate the prevalence of BE to be 5.6% (5.49-5.70%). Using our model, an estimated prevalence for BE in the general population of 5.6% (5.49-5.70%) accurately predicts incidence rates for EAC reported to the US SEER cancer registry. Future clinical studies are needed to confirm our estimate. C1 [Hayeck, T. J.; Kong, C. Y.; Gazelle, G. S.; Hur, C.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Hayeck, T. J.; Hur, C.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Kong, C. Y.; Gazelle, G. S.; Hur, C.] Harvard Univ, Sch Med, Boston, MA USA. [Spechler, S. J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 FU NIH/NCI [CA107060] FX NIH/NCI Grant CA107060 (C.H.). No potential financial conflicts to report. NR 34 TC 46 Z9 48 U1 2 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1120-8694 J9 DIS ESOPHAGUS JI Dis. Esophagus PD AUG PY 2010 VL 23 IS 6 BP 451 EP 457 DI 10.1111/j.1442-2050.2010.01054.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 641NQ UT WOS:000281135000003 PM 20353441 ER PT J AU Green, TC Kershaw, T Lin, HQ Heimer, R Goulet, JL Kraemer, KL Gordon, AJ Maisto, SA Day, NL Bryant, K Fiellin, DA Justice, AC AF Green, Traci C. Kershaw, Trace Lin, Haiqun Heimer, Robert Goulet, Joseph L. Kraemer, Kevin L. Gordon, Adam J. Maisto, Steve A. Day, Nancy L. Bryant, Kendall Fiellin, David A. Justice, Amy C. TI Patterns of drug use and abuse among aging adults with and without HIV: A latent class analysis of a US Veteran cohort SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Aging; Veterans; HIV; Substance-related disorders; Latent class analysis; Illicit drugs; Cohort studies ID ACTIVE ANTIRETROVIRAL THERAPY; SUBSTANCE USE DISORDERS; VIRUS-INFECTED VETERANS; HEALTH-CARE UTILIZATION; NEW-YORK-CITY; DEVELOPMENTAL TRAJECTORIES; YOUNG ADULTHOOD; UNITED-STATES; MARIJUANA USE; OLDER-ADULTS AB This study characterized the extent and patterns of self-reported drug use among aging adults with and without HIV, assessed differences in patterns by HIV status, and examined pattern correlates. Data derived from 6351 HIV-infected and uninfected adults enrolled in an eight-site matched cohort, the Veterans Aging Cohort Study (VACS). Using clinical variables from electronic medical records and socio-demographics, drug use consequences, and frequency of drug use from baseline surveys, we performed latent class analyses (LCA) stratified by HIV status and adjusted for clinical and socio-demographic covariates. Participants were, on average, age 50 (range 22-86), primarily male (95%) and African-American (64%). Five distinct patterns emerged: non-users, past primarily marijuana users, past multidrug users, current high consequence multidrug users, and current low consequence primarily marijuana users. HIV status strongly influenced class membership. Non-users were most prevalent among HIV uninfected (36.4%) and current high consequence multidrug users (25.5%) were most prevalent among HIV-infected. While problems of obesity marked those not currently using drugs, current users experienced higher prevalences of medical or mental health disorders. Multimorbidity was highest among past and current multidrug users. HIV-infected participants were more likely than HIV-uninfected participants to be current low consequence primarily marijuana users. In this sample, active drug use and abuse were common. HIV-infected and uninfected Veterans differed on extent and patterns of drug use and on important characteristics within identified classes. Findings have the potential to inform screening and intervention efforts in aging drug users with and without HIV. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Green, Traci C.; Kershaw, Trace] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA. [Green, Traci C.; Kershaw, Trace; Heimer, Robert; Goulet, Joseph L.; Fiellin, David A.; Justice, Amy C.] Yale Ctr Interdisciplinary Res AIDS, New Haven, CT USA. [Lin, Haiqun] Yale Univ, Sch Publ Hlth, Div Biostat, New Haven, CT USA. [Heimer, Robert] Yale Univ, Sch Publ Hlth, Div Epidemiol Microbial Dis, New Haven, CT USA. [Goulet, Joseph L.; Justice, Amy C.] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Goulet, Joseph L.; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Kraemer, Kevin L.; Gordon, Adam J.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr Comorbid VISN, Pittsburgh, PA USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Maisto, Steve A.] Syracuse Univ, Dept Psychol, Ctr Hlth & Behav, Syracuse, NY USA. [Day, Nancy L.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Bryant, Kendall] NIAAA, Bethesda, MD USA. [Fiellin, David A.] Yale Univ, Sch Med, Investigat Med Program, New Haven, CT USA. RP Green, TC (reprint author), 111 Plain St Bldg,Rm 111, Providence, RI 02903 USA. EM traci.c.green@brown.edu RI Day, Nancy/H-3171-2016; OI Goulet, Joseph/0000-0002-0842-804X; Fiellin, David/0000-0002-4006-010X FU National Institutes of Health, National Institute on Drug Abuse [1F31DA023862-01A1]; National Institute on Alcohol Abuse and Alcoholism [U10 AA 13566]; VHA Public Health Strategic Health Core Group FX Research for this manuscript was supported by the National Institutes of Health, National Institute on Drug Abuse grant 1F31DA023862-01A1 to TCG. The Veterans Aging Cohort Study funded by: National Institute on Alcohol Abuse and Alcoholism (U10 AA 13566) and VHA Public Health Strategic Health Core Group. The funding sources had no further involvement in the study design, data collection, analysis, writing, preparation or decision to submit this manuscript for publication. NR 94 TC 37 Z9 37 U1 2 U2 11 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 AUG 1 PY 2010 VL 110 IS 3 BP 208 EP 220 DI 10.1016/j.drugalcdep.2010.02.020 PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 634ZU UT WOS:000280626200005 PM 20395074 ER PT J AU George, E Becerra, L Upadhyay, J Schmidt, U Borsook, D AF George, Edward Becerra, Lino Upadhyay, Jaymin Schmidt, Ulrich Borsook, David TI Evaluation of novel drugs using fMRI in early-phase clinical trials: safety monitoring SO DRUG DISCOVERY TODAY LA English DT Review ID FUNCTIONAL MRI; NEURAL BASIS; EXPERIENCE; BENEFIT; FUTURE AB A advances in functional magnetic resonance imaging (fMRI) permit the possibility of helping with dose ranging, as well as potential drug efficacy and side-effect profiles. However there are no current guidelines or standards for fMRI that meet established standards of care. Guidelines must be adopted to be used when patients are exposed to novel drugs, in particular, when immediate access to the patient is limited. When used in initial, MRI mandates certain safety standards because subjects are positioned in the magnet thereby limiting direct observation, communication or immediate access in an emergency; in testing new drugs using fMRI, we suggest that safety guidelines merit discussion and definition. This could lead to the adoption of standards. Some of these issues are unique to the application of the technology in early-phase trials. C1 [George, Edward; Becerra, Lino; Upadhyay, Jaymin] Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. [George, Edward; Schmidt, Ulrich] Harvard Univ, Sch Med, McLean Hosp, Dept Anesthesia,Brain Imaging Ctr, Belmont, MA 02478 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Mclean & Massachusetts Gen Hosp, Dept Psychiat,Brain Imaging Ctr,McLean Hosp, Belmont, MA 02478 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Brain Imaging Ctr,McLean Hosp, Belmont, MA 02478 USA. RP George, E (reprint author), Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. EM edgeorge@partners.org FU L Herlands fund for pain research; K24 NINDS [NS064050] FX Supported by the L Herlands fund for pain research (D.B. and L.B.) and K24 NINDS NS064050 (D.B.). NR 23 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD AUG PY 2010 VL 15 IS 15-16 BP 684 EP 689 DI 10.1016/j.drudis.2010.05.008 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641OU UT WOS:000281138600013 PM 20553959 ER PT J AU Milsom, MD Williams, DA AF Milsom, Michael D. Williams, David A. TI Gaining the hard yard: pre-clinical evaluation of lentiviral-mediated gene therapy for the treatment of beta-thalassemia SO EMBO MOLECULAR MEDICINE LA English DT Editorial Material DE gene therapy; haematopoiesis; insertional mutagenesis; lentivirus; beta-thalassemia ID SCID-X1 AB Gene therapy is one potential novel therapeutic avenue for the treatment of inherited monogenic disorders. Diseases of the blood are frequent targets for gene therapy because it is relatively easy to harvest haematopoietic stem cells (HSCs) from the bone marrow, genetically modify the cells ex vivo, and then re-administer the corrected cells back into the patient via intra-venous injection. In this Closeup, Milsom and Williams discuss the work of Roselli et al, who describe the pre-clinical evaluation of the treatment for beta-thalassemia in erythroid cells via the genetic correction of patient HSCs using a lentiviral vector. C1 [Milsom, Michael D.; Williams, David A.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Milsom, Michael D.; Williams, David A.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Milsom, Michael D.; Williams, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Williams, David A.] Harvard Stem Cell Inst, Boston, MA USA. [Williams, David A.] Dana Farber Canc Inst, Brookline, MA USA. RP Williams, DA (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM dawilliams@childrens.harvard.edu NR 6 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD AUG PY 2010 VL 2 IS 8 BP 291 EP 293 DI 10.1002/emmm.201000086 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 646ER UT WOS:000281520500002 PM 20677209 ER PT J AU Wang, N Guo, LK Rueda, BR Tilly, JL AF Wang, Ning Guo, Lankai Rueda, Bo R. Tilly, Jonathan L. TI Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress SO EMBO REPORTS LA English DT Article DE p63; Cables1; proteasome; oocyte; apoptosis ID MOUSE OOCYTES; C-ABL; PHOSPHORYLATION; EXPRESSION; CANCER; DEATH; MICE; WEE1; P73 AB The p63 gene product regulates epithelial morphogenesis and female germline integrity. In this study, we show that cyclin-dependent kinase 5 and Abl enzyme substrate 1 (Cables1) interacts with the trans-activating (TA) p63 alpha isoform to protect it from proteasomal degradation. Using the female germline of Cables1-null mice as an in vivo model, we demonstrate further that oocytes lacking Cables1 exhibit lower basal levels of TAp63 alpha and reduced accumulation of phosphorylated TAp63 alpha in response to genotoxic stress. This in turn enhances the survival of these cells after ionizing radiation exposure. Thus, Cables1 modulates p63 protein stability and function during genotoxic stress. C1 [Wang, Ning; Guo, Lankai; Rueda, Bo R.; Tilly, Jonathan L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, THR 901B,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org FU Massachusetts General Hospital; National Institute on Aging [R37-AG012279]; National Institutes of Health [R01-CA098333]; Henry and Vivian Rosenberg Philanthropic Fund; Sea Breeze Foundation; Vincent Memorial Research Funds FX We thank F. McKeon for TAp63 antibody and T. Ohta for helpful discussions regarding the ubiquitination assay. N.W. is a recipient of a Massachusetts General Hospital Fund for Medical Discovery award. This study was supported by National Institute on Aging MERIT Award R37-AG012279, National Institutes of Health R01-CA098333, the Henry and Vivian Rosenberg Philanthropic Fund, the Sea Breeze Foundation and Vincent Memorial Research Funds. NR 26 TC 10 Z9 10 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD AUG PY 2010 VL 11 IS 8 BP 633 EP 639 DI 10.1038/embor.2010.82 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 630YS UT WOS:000280313400017 PM 20559324 ER PT J AU Ouyang, H Quinn, J AF Ouyang, Helen Quinn, James TI Diagnosis and Evaluation of Syncope in the Emergency Department SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Article DE Syncope; Diagnosis; Evaluation; Prognosis ID CAROTID-SINUS SYNDROME; LONG QT SYNDROME; HYPERTROPHIC CARDIOMYOPATHY; CLINICAL CHARACTERISTICS; ORTHOSTATIC HYPOTENSION; UNEXPLAINED SYNCOPE; BLOOD-PRESSURE; POPULATION; RULE; MANAGEMENT AB With a careful history, physical examination, and directed investigation, physicians can determine the likely cause of syncope in more than 50% and perhaps up to 80% of patients. Understanding the cause of syncope allows clinicians to determine the disposition of high- and low-risk patients. Patients with a potential malignant cause, such as a cardiac or neurologic condition, should be treated and admitted. Those with benign causes can be safely discharged. This article reviews the diagnosis and ED work-up of syncope, the different classifications of syncope, and prognosis The use of specific decision rules in risk stratification and syncope in the pediatric population are discussed in another article C1 [Ouyang, Helen] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Ouyang, Helen] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Quinn, James] Stanford Univ, Div Emergency Med, Palo Alto, CA 94304 USA. RP Ouyang, H (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville House, Boston, MA 02115 USA. NR 67 TC 3 Z9 4 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8627 EI 1558-0539 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD AUG PY 2010 VL 28 IS 3 BP 471 EP + DI 10.1016/j.emc.2010.03.007 PG 16 WC Emergency Medicine SC Emergency Medicine GA 649AN UT WOS:000281737700005 PM 20709239 ER PT J AU Fugate, JMB Gouzoules, H Barrett, LF AF Fugate, Jennifer M. B. Gouzoules, Harold Barrett, Lisa Feldman TI Reading Chimpanzee Faces: Evidence for the Role of Verbal Labels in Categorical Perception of Emotion SO EMOTION LA English DT Article DE facial expressions; emotion; categorical perception; verbal labeling; expertise ID NEWLY LEARNED FACES; FACIAL EXPRESSIONS; 12-MONTH-OLD INFANTS; CATEGORIZATION; DISCRIMINATION; RECOGNITION; INVITATIONS; LANGUAGE; MUSCLES; WORDS AB Categorical perception (CP) occurs when continuously varying stimuli are perceived as belonging to discrete categories. Thereby, perceivers are more accurate at discriminating between stimuli of different categories than between stimuli within the same category (Hamad, 1987; Goldstone, 1994). The current experiments investigated whether the structural information in the face is sufficient for CP to occur. Alternatively, a perceiver's conceptual knowledge, by virtue of expertise or verbal labeling, might contribute. In two experiments, people who differed in their conceptual knowledge (in the form of expertise, Experiment 1; or verbal label learning, Experiment 2) categorized chimpanzee facial expressions. Expertise alone did not facilitate CP. Only when perceivers first explicitly learned facial expression categories with a label were they more likely to show CP. Overall, the results suggest that the structural information in the face alone is often insufficient for CP; CP is facilitated by verbal labeling. C1 [Fugate, Jennifer M. B.; Barrett, Lisa Feldman] Boston Coll, Dept Psychol, Chestnut Hill, MA 02467 USA. [Gouzoules, Harold] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Barrett, Lisa Feldman] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Fugate, JMB (reprint author), Boston Coll, Dept Psychol, 140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM fugatej@bc.edu FU NIH HHS [DP1 OD003312-01, DP1OD003312, DP1 OD003312]; NIMH NIH HHS [F32 MH083455] NR 40 TC 13 Z9 14 U1 0 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD AUG PY 2010 VL 10 IS 4 BP 544 EP 554 DI 10.1037/a0019017 PG 11 WC Psychology, Experimental SC Psychology GA 637PE UT WOS:000280829700009 PM 20677871 ER PT J AU Guo, J Liu, ML Yang, DH Bouxsein, ML Thomas, CC Schipani, E Bringhurst, FR Kronenberg, HM AF Guo, Jun Liu, Minlin Yang, Dehong Bouxsein, Mary L. Thomas, Clare C. Schipani, Ernestina Bringhurst, F. Richard Kronenberg, Henry M. TI Phospholipase C Signaling via the Parathyroid Hormone (PTH)/PTH-Related Peptide Receptor Is Essential for Normal Bone Responses to PTH SO ENDOCRINOLOGY LA English DT Article ID GROWTH-PLATE CHONDROCYTES; RAT OSTEOBLASTIC CELLS; PROTEIN-KINASE; IN-VIVO; PTH/PTHRP RECEPTOR; ADENYLYL-CYCLASE; LLC-PK1 CELLS; DIFFERENTIATION; PROLIFERATION; INTERMITTENT AB We have previously shown that differentiation of hypertrophic chondrocytes is delayed in mice expressing a mutated PTH/PTHrP receptor (PTHR) (called DSEL here) that stimulates adenylyl cyclase normally but fails to activate phospholipase C (PLC). To better understand the role of PLC signaling via the PTHR in skeletal and mineral homeostasis, we examined these mice fed a normal or calcium-deficient diet. On a standard diet, DSEL mice displayed a modest decrease in bone mass. Remarkably, when fed a low-calcium diet or infused with PTH, DSEL mice exhibited strikingly curtailed peritrabecular stromal cell responses and attenuated new bone formation when compared with Wt mice. Attenuated in vitro colony formation was also observed in bone marrow cells derived from DSEL mice fed a low-calcium diet. Furthermore, PTH stimulated proliferation and increased mRNAs encoding cyclin D1 in primary osteoblasts derived from Wt but not from DSEL mice. Our data indicate that PLC signaling through the PTHR is required for skeletal homeostasis. (Endocrinology 151: 3502-3513, 2010) C1 [Guo, Jun; Liu, Minlin; Yang, Dehong; Thomas, Clare C.; Schipani, Ernestina; Bringhurst, F. Richard; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab, Boston, MA 02215 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM hkronenberg@partners.org FU National Institutes of Health [DK11794] FX This work was supported by National Institutes of Health Grant DK11794 (to H.M.K.). NR 45 TC 28 Z9 34 U1 2 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2010 VL 151 IS 8 BP 3502 EP 3513 DI 10.1210/en.2009-1494 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 629CH UT WOS:000280171100005 PM 20501677 ER PT J AU D'Andrea, AD AF D'Andrea, A. D. TI The Fanconi Anemia Pathway in DNA Interstrand Crosslink Repair SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [D'Andrea, A. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [D'Andrea, A. D.] Harvard Univ, Sch Med, Boston, MA USA. [D'Andrea, A. D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 687 EP 687 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600014 ER PT J AU Price, BD AF Price, B. D. TI Histone Methylation The Link between Chromatin Structure and DNA Repair SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 41st Annual Meeting of Environmental-Mutagen-Society CT 41st Annual Meeting of Complex Systems in Biology and Risk Assessment CY OCT 23-27, 2010 CY OCT 23-27, 2010 CL Ft Worth, TX CL Ft Worth, TX SP Environ Mutagen Soc SP Environ Mutagen Soc C1 [Price, B. D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2010 VL 51 IS 7 BP 699 EP 699 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 639XE UT WOS:000281009600062 ER PT J AU Leeman, BA AF Leeman, Beth A. TI Remote memory deficits in epilepsy and the role of failed consolidation SO EPILEPSY & BEHAVIOR LA English DT Letter C1 [Leeman, Beth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Leeman, Beth A.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Leeman, Beth A.] Harvard Univ, Sch Med, Boston, MA USA. RP Leeman, BA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM baleeman@partners.org OI Macklin, Eric/0000-0003-1618-3502 NR 5 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD AUG PY 2010 VL 18 IS 4 BP 498 EP 499 DI 10.1016/j.yebeh.2010.03.003 PG 2 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 643ON UT WOS:000281306600027 PM 20708577 ER PT J AU Roberts, JD Davies, RW Lubitz, SA Thibodeau, IL Nery, PB Birnie, DH Benjamin, EJ Lemery, R Ellinor, PT Gollob, MH AF Roberts, Jason D. Davies, Robert W. Lubitz, Steven A. Thibodeau, Isabelle L. Nery, Pablo B. Birnie, David H. Benjamin, Emelia J. Lemery, Robert Ellinor, Patrick T. Gollob, Michael H. TI Evaluation of non-synonymous NPPA single nucleotide polymorphisms in atrial fibrillation SO EUROPACE LA English DT Article DE Atrial fibrillation; Atrial natriuretic peptide; Single nucleotide polymorphism; Genetics ID OF-FUNCTION MUTATION; BLOOD-PRESSURE PROGRESSION; NATRIURETIC-PEPTIDE; FAMILIAL AGGREGATION; INCIDENT HYPERTENSION; GENE POLYMORPHISMS; ISCHEMIC-STROKE; HEART-DISEASE; RISK-FACTOR; VARIANTS AB Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an important cause of morbidity and mortality. A genetic mutation in the NPPA gene, which encodes the atrial natriuretic peptide, has been identified as the putative causative factor in a family with an autosomal dominant pattern of inheritance for AF. Two common single nucleotide polymorphisms (SNPs) in NPPA, rs5063 and rs5065, result in amino acid changes of the primary peptide and have been previously implicated in conditions associated with AF, including stroke and hypertension. Recently, the rs5063 SNP has been reported to confer an increased risk of AF development in a Chinese population. We sought to examine the associations of both rs5063 and rs5065 with AF in two separate North American cohorts of European ancestry. Patients with early-onset AF, along with healthy controls, were recruited at the University of Ottawa Heart Institute (UOHI) and the Massachusetts General Hospital (MGH). Study participants were genotyped for rs5063 and rs5065 using a combination of restriction fragment length polymorphism analysis and DNA microarrays. The study genotyped a total of 620 AF cases and 2446 healthy controls. The UOHI arm of the study identified an odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.42-1.24] for rs5063, whereas an OR of 1.33 (95% CI: 0.80-2.21) was observed in the MGH arm. The combined OR approximated unity (OR 0.99; 95% CI: 0.54-1.80). Analysis of rs5065 revealed an OR of 1.12 (95% CI: 0.84-1.48) in UOHI, 1.08 (95% CI 0.80-1.45) in MGH, and 1.10 (95% CI 0.90-1.35) when combined. Common non-synonymous genetic variants within NPPA in these two large North American cohorts of European ancestry are not associated with the development of AF. C1 [Roberts, Jason D.; Thibodeau, Isabelle L.; Gollob, Michael H.] Univ Ottawa, Inst Heart, Arrhythmia Res Lab, Ottawa, ON K1Y 4W7, Canada. [Davies, Robert W.] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON K1Y 4W7, Canada. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Nery, Pablo B.; Birnie, David H.; Lemery, Robert; Gollob, Michael H.] Univ Ottawa, Inst Heart, Arrhythmia Serv, Ottawa, ON K1Y 4W7, Canada. [Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol & Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP Gollob, MH (reprint author), Univ Ottawa, Inst Heart, Arrhythmia Res Lab, 40 Ruskin St, Ottawa, ON K1Y 4W7, Canada. EM mgollob@ottawaheart.ca RI Nery, Pablo/D-1754-2011; OI Benjamin, Emelia/0000-0003-4076-2336 FU Heart and Stroke Foundation of Ontario; Canadian Institutes of Health Research; NIH [HL092577, RC1-HL01056, DA027021, T32HL00757] FX This work was supported by grants from the Heart and Stroke Foundation of Ontario and Canadian Institutes of Health Research to M.H.G. and grants from the NIH: HL092577 to P.T.E. and E.J.B.; RC1-HL01056 to E.J.B.; and DA027021 to P.T.E.; S.A.L. was supported by a training grant from the NIH (T32HL00757). NR 42 TC 13 Z9 13 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD AUG PY 2010 VL 12 IS 8 BP 1078 EP 1083 DI 10.1093/europace/euq161 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 633VV UT WOS:000280535800009 PM 20543198 ER PT J AU Hildebrandt, P Collinson, PO Doughty, RN Fuat, A Gaze, DC Gustafsson, F Januzzi, J Rosenberg, J Senior, R Richards, M AF Hildebrandt, Per Collinson, Paul O. Doughty, Robert N. Fuat, Ahmet Gaze, David C. Gustafsson, Finn Januzzi, James Rosenberg, Jens Senior, Roxy Richards, Mark TI Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care(dagger) SO EUROPEAN HEART JOURNAL LA English DT Article DE Natriuretic peptides; Chronic heart failure; Diagnosis; Decision limits ID HEART-FAILURE; PRIMARY-CARE; DIAGNOSTIC-ACCURACY; METAANALYSIS; POPULATION; PROGNOSIS; STATEMENT; COMMUNITY; SURVIVAL; MARKER AB The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards. Data were obtained from 5508 patients from 10 studies in the UK, New Zealand, Europe, and USA. All have had NT-proBNP analysis and echocardiography. The median age was 62 years (range 18-100 years) with a prevalence of reduced left ventricular systolic function (left ventricular ejection fraction < 40%) of 18%. In a receiver operating characteristic curve analysis, overall area under the curve (AUC) was 0.89. When looking at different age groups, AUC was highest (0.95) for < 50 years, intermediate (0.90) for 50-75 years, and lowest (0.82) for > 75 years. Using optimized decision limits, sensitivity, specificity, and negative predictive values (NPVs) were: < 50 years (50 ng/L): 99.2, 57.2, and 99.7%; 50-75 years (75 ng/L): 95.9, 51.0, and 96.8%; and > 75 years (250 ng/L): 87.9, 53.7, and 92.4%, respectively. Using only a single decision value (125 ng/L for all ages) gave sensitivities of 89.1, 91.9, and 94.3%; specificities of 84.0, 69.1, and 29.3% and NPVs of 97.7, 97.6, and 93.4%. A decision value of 400 ng/L for all ages gave much lower sensitivities. In a large population of patients in primary care, the use of age-stratified NT-proBNP decision limits considerably improves performance over current standards, with an excellent NPV for exclusion of reduced left ventricular systolic function. C1 [Hildebrandt, Per] Glostrup Univ Hosp, Dept Cardiol & Med, Glostrup, Denmark. [Collinson, Paul O.; Gaze, David C.] St George Hosp, Dept Chem Pathol, London, England. [Collinson, Paul O.] St George Hosp, Dept Cardiol, London, England. [Doughty, Robert N.] Univ Auckland, Dept Med, Fac Med & Hlth Sci, Auckland, New Zealand. [Fuat, Ahmet] Univ Durham, Dept Cardiol, Darlington Mem Hosp, Ctr Integrated Hlth Care Res, Durham, England. [Gustafsson, Finn] State Univ Hosp, Dept Cardiol, Copenhagen, Denmark. [Januzzi, James] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Rosenberg, Jens] Frederiksberg Univ Hosp, Dept Cardiol & Endocrinol, Frederiksberg, Denmark. [Senior, Roxy] Northwick Pk Hosp & Clin Res Ctr, Dept Cardiol, Middlesex, England. [Richards, Mark] Christchurch Sch Med & Hlth Sci, Christchurch Cardioendocrine Res Grp, Christchurch, New Zealand. RP Hildebrandt, P (reprint author), Glostrup Univ Hosp, Dept Cardiol & Med, Glostrup, Denmark. EM p.hildebrandt@dadlnet.dk OI Gustafsson, Finn/0000-0003-2144-341X FU Roche Diagnostics FX P.H., P.O.C., R.N.D., J.J., and M.R. received research support from Roche Diagnostics. NR 33 TC 41 Z9 42 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2010 VL 31 IS 15 BP 1881 EP 1889 DI 10.1093/eurheartj/ehq163 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 636CA UT WOS:000280704300014 PM 20519241 ER PT J AU Hjortnaes, J Butcher, J Figueiredo, JL Riccio, M Kohler, RH Kozloff, KM Weissleder, R Aikawa, E AF Hjortnaes, Jesper Butcher, Jonathan Figueiredo, Jose-Luiz Riccio, Mark Kohler, Rainer H. Kozloff, Kenneth M. Weissleder, Ralph Aikawa, Elena TI Arterial and aortic valve calcification inversely correlates with osteoporotic bone remodelling: a role for inflammation SO EUROPEAN HEART JOURNAL LA English DT Article DE Aortic valve calcification; Atherosclerosis; Inflammation; Bone mineral density; Molecular imaging ID VASCULAR CALCIFICATION; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; DEFICIENT MICE; DISEASE; CELLS; OSTEOPROTEGERIN; PLAQUE; MECHANISMS; MATRIX AB Aims Westernized countries face a growing burden of cardiovascular calcification and osteoporosis. Despite its vast clinical significance, the precise nature of this reciprocal relationship remains obscure. We hypothesize that cardiovascular calcification progresses with inflammation and inversely correlates with bone tissue mineral density (TMD). Methods and results Arterial, valvular, and bone metabolism were visualized using near-infrared fluorescence (NIRF) molecular imaging agents, targeting macrophages and osteogenesis. We detected significant arterial and aortic valve calcification in apoE(-/-) mice with or without chronic renal disease (CRD, 30 weeks old; n = 28), correlating with the severity of atherosclerosis. We demonstrated decreases in osteogenic activity in the femurs of apoE(-/-) mice when compared with WT mice, which was further reduced with CRD. Three-dimensional micro-computed tomography imaging of the cortical and cancellous regions of femurs quantified structural remodelling and reductions in TMD in apoE(-/-) and CRD apoE(-/-) mice. We established significant correlations between arterial and valvular calcification and loss of TMD (R(2) = 0.67 and 0.71, respectively). Finally, we performed macrophage-targeted molecular imaging to explore a link between inflammation and osteoporosis in vivo. Although macrophage burden, visualized as uptake of NIRF-conjugated iron nanoparticles, was directly related to the degree of arterial and valvular inflammation and calcification, the same method inversely correlated inflammation with TMD (R(2) = 0.73; 0.83; 0.75, respectively). Conclusion This study provides direct in vivo evidence that in arteries and aortic valves, macrophage burden and calcification associate with each other, whereas inflammation inversely correlates with bone mineralization. Thus, understanding inflammatory signalling mechanisms may offer insight into selective abrogation of divergent calcific phenomena. C1 [Hjortnaes, Jesper; Figueiredo, Jose-Luiz; Kohler, Rainer H.; Weissleder, Ralph; Aikawa, Elena] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Butcher, Jonathan] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA. [Butcher, Jonathan; Riccio, Mark] Cornell Univ, Preclin Imaging Facil, Ithaca, NY USA. [Figueiredo, Jose-Luiz; Aikawa, Elena] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kozloff, Kenneth M.] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA. RP Aikawa, E (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. EM eaikawa@partners.org RI Butcher, Jonathan/D-2280-2012 OI Butcher, Jonathan/0000-0002-9309-6296 FU Wijck-Casper-Stam Foundation; American Heart Association [0835460N, 0830384N]; NYSTAR CAT Award; Donald W. Reynolds Foundation; Leducq Foundation [07CVD04]; Translational Program of Excellence in Nanotechnology [5-UO1-HL080731] FX This study was supported in part by Wijck-Casper-Stam Foundation (J.H.), American Heart Association Scientist Development Grants (0835460N, E.A.; 0830384N, J.B.), NYSTAR CAT Award (J.B., M.R.), Donald W. Reynolds Foundation (R.W., E.A.), Leducq Foundation (07CVD04; E.A., J.B.) and Translational Program of Excellence in Nanotechnology (5-UO1-HL080731; R.W.). Funding to pay the Open Access publication charges for this article was provided by research grants to Dr Aikawa. NR 39 TC 80 Z9 88 U1 1 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2010 VL 31 IS 16 BP 1975 EP 1984 DI 10.1093/eurheartj/ehq237 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 643IP UT WOS:000281289100012 PM 20601388 ER PT J AU Scirica, BM Morrow, DA Bode, C Ruzyllo, W Ruda, M Ophuis, AJMO Lopez-Sendon, J Swedberg, K Ogorek, M Rifai, N Lukashevich, V Maboudian, M Cannon, CP McCabe, CH Braunwald, E AF Scirica, Benjamin M. Morrow, David A. Bode, Christoph Ruzyllo, Witold Ruda, Mikhail Ophuis, Anthonius J. M. Oude Lopez-Sendon, Jose Swedberg, Karl Ogorek, Michal Rifai, Nader Lukashevich, Valentina Maboudian, Mojdeh Cannon, Christopher P. McCabe, Carolyn H. Braunwald, Eugene TI Patients with acute coronary syndromes and elevated levels of natriuretic peptides: the results of the AVANT GARDE-TIMI 43 Trial SO EUROPEAN HEART JOURNAL LA English DT Article DE Natriuretic peptides; Acute coronary syndrome; Renin-angiotensin-aldosteron system ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR DYSFUNCTION; RENIN INHIBITOR ALISKIREN; HEART-FAILURE; PROGNOSTIC VALUE; ARTERY-DISEASE; DOUBLE-BLIND; ANTIHYPERTENSIVE EFFICACY; ORAL CAPTOPRIL; MORTALITY AB Aims Elevated natriuretic peptides (NPs) are associated with an increased cardiovascular risk following acute coronary syndromes (ACSs). However, the therapeutic implications are still undefined. We hypothesized that early inhibition of renin angiotensin aldosterone system (RAAS) in patients with preserved left ventricular function but elevated NPs but following ACS would reduce haemodynamic stress as reflected by a greater reduction NP compared with placebo. Methods and results AVANT GARDE-TIMI 43 trial, a multinational, double-blind trial, randomized 1101 patients stabilized after ACS without clinical evidence of heart failure or left ventricular function <= 40% but with an increased level of NP 3-10 days after admission to aliskiren, valsartan, their combination, and placebo. The primary endpoint was the change in NT-proBNP from baseline to Week 8. NT-proBNP declined significantly in each treatment arm, including placebo, by Week 8, though there were no differences in the reduction between treatment strategies (42% in placebo, 44% in aliskiren, 39% in valsartan, and 36% in combination arm). Although several subgroups had higher baseline levels of NP and greater reductions over the study period, there were no differences among treatment groups in any subgroup. There were no differences in clinical outcomes but there were more adverse events, including serious events and adverse events leading to early study drug discontinuation, in patients treated with active therapy. Conclusion In this study of a high-risk population with elevated levels of NPs but relatively preserved systolic function and no evidence of heart failure following ACS, there was no evidence for a benefit of early initiation of inhibition of RAAS with valsartan, aliskiren, or their combination compared with placebo with respect to a reduction in NP over 8 weeks of therapy. Moreover, adverse events were reported more frequently in patients assigned to active therapy. C1 [Scirica, Benjamin M.; Morrow, David A.; Cannon, Christopher P.; McCabe, Carolyn H.; Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Scirica, Benjamin M.; Morrow, David A.; Cannon, Christopher P.; McCabe, Carolyn H.; Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA. [Bode, Christoph] Med Univ Klin, Freiburg, Germany. [Ruzyllo, Witold] Inst Cardiol, Warsaw, Poland. [Ruda, Mikhail] Cardiol Res Ctr, Moscow 121552, Russia. [Ophuis, Anthonius J. M. Oude] Canisiud Wilhelmina Ziekenhuis, Nijmegen, Netherlands. [Lopez-Sendon, Jose] Hosp Univ La Paz, Madrid, Spain. [Swedberg, Karl] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. [Ogorek, Michal] Samodzielny Szpital Wojewodzki, Piotrkow Trybunalski, Poland. [Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Lukashevich, Valentina; Maboudian, Mojdeh] Novartis Pharmaceut, E Hanover, NJ USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org FU CV Therapeutics; Novartis; AstraZeneca; Daiichi-Sankyo; Bristol Meyer-Squibb; Roche Diagnostics; Michael Lerner Foundation; Otsuka; Servier FX B.M.S. reports research support from CV Therapeutics, Novartis, AstraZeneca, Daiichi-Sankyo, Bristol Meyer-Squibb, and Roche Diagnostics, honoraria for educational presentations from CV Therapeutics, Novartis, Merck, Schering-Plough, sanofi-aventis, Lilly, Daiichi-Sankyo, has served as a consultant for AstraZeneca, Novartis, and Cogentus and received an unrestricted research grant from the Michael Lerner Foundation. D.M.M. has received honoraria for educational presentations from CV Therapeutics and Eli Lilly has served as a consultant for Beckman-Coulter, Critical Diagnostics, Genentech, Ikaria, Menarini, OrthoClinical Diagnostics, Roche Diagnostics, Sanofi Aventis, Schering Plough, and Siemens, and was compensated as a member of a Clinical Events Committee for a clinical trial by AstraZeneca. J.L.-S. has received research grants from Novartis. K.S. reports having research support and honoraria from Astrazeneca, Novartis, Otsuka, Servier. V.L. and M.M. are employees of Novartis. C.P.C. reports research funding from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, Glaxo Smith Kline, Intekrin Therapeutics, Merck, Merck/Schering Plough Partnership, Novartis, and Takeda and acted as a Clinical Advisor and having equity in Automedics Medical Systems. E.B. has received honoraria from Bristol Myers Squibb, Merck, and Pfizer and has served as a consultant to Bristol-Myers Squibb, and Pfizer. Others report no conflicts. NR 30 TC 30 Z9 32 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2010 VL 31 IS 16 BP 1993 EP 2005 DI 10.1093/eurheartj/ehq190 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 643IP UT WOS:000281289100014 PM 20558431 ER PT J AU Brick, DJ Gerweck, AV Meenaghan, E Lawson, EA Misra, M Fazeli, P Johnson, W Klibanski, A Miller, KK AF Brick, D. J. Gerweck, A. V. Meenaghan, E. Lawson, E. A. Misra, M. Fazeli, P. Johnson, W. Klibanski, A. Miller, K. K. TI Determinants of IGF1 and GH across the weight spectrum: from anorexia nervosa to obesity SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE-SECRETION; FACTOR-I; CARDIOVASCULAR RISK; REPLACEMENT THERAPY; NORMAL WOMEN; TESTOSTERONE; DEFICIENCY; AXIS; AGE; OVERWEIGHT AB Context: Chronic starvation is characterized by GH resistance, and obesity is characterized by decreased GH secretion. In both extremes, IGF1 levels may be low and androgen levels may be abnormal. Objective: To investigate the determinants of IGF1 and GH across the weight spectrum in women. Design: Cross-sectional study. Setting: Clinical research center. Study participants: In total, 32 women had participated in the study: 11 women with anorexia nervosa (AN), 11 normal-weight women, and 10 obese women of comparable mean age. Intervention: None. Main outcome measures: Pooled hourly overnight serum samples assayed for IGF1, GH, estradiol (E-2), testosterone, SHBG, insulin, free fatty acids, and trunk fat. Results: Free testosterone was higher in obese women and lower in women with AN than in normal-weight women, and was the only independent (and positive) predictor of IGF1 levels, accounting for 14% of the variability (P=0.032) in the group as a whole. This relationship was stronger when obese women were excluded, with free testosterone accounting for 36% of the variability (P=0.003). Trunk fat accounted for 49% of the variability (P<0.0001) of GH, with an additional 7% of the variability attributable to E-2 (P=0.042) in the group as a whole, but was not a significant determinant of GH secretion when obese women were excluded. Conclusions: Free testosterone is a significant determinant of IGF1 levels in women across the body weight spectrum. In contrast, GH secretion is differentially regulated at the extremes of the weight spectrum. C1 [Miller, K. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@partners.org RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NIH [R01 HL077674, R01 DK52525, MO1 RR01066, UL1 RR025758] FX This work was supported in part by the following NIH grants: R01 HL077674, R01 DK52525, MO1 RR01066, and UL1 RR025758. NR 31 TC 14 Z9 14 U1 1 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 EI 1479-683X J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD AUG PY 2010 VL 163 IS 2 BP 185 EP 191 DI 10.1530/EJE-10-0365 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 633FJ UT WOS:000280484800002 PM 20501597 ER PT J AU Dhingra, R Gona, P Benjamin, EJ Wang, TJ Aragam, J D'Agostino, RB Kannel, WB Vasan, RS AF Dhingra, Ravi Gona, Philimon Benjamin, Emelia J. Wang, Thomas J. Aragam, Jayashri D'Agostino, Ralph B., Sr. Kannel, William B. Vasan, Ramachandran S. TI Relations of serum phosphorus levels to echocardiographic left ventricular mass and incidence of heart failure in the community SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Phosphorus; Congestive heart failure; Ventricle; Epidemiology; Risk factors ID PARATHYROID-HORMONE SECRETION; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; PHOSPHATE LEVEL; RISK; ASSOCIATION; FRAMINGHAM; 1,25-DIHYDROXYVITAMIN-D; HYPERPHOSPHATEMIA; SUPPLEMENTATION AB Aims To evaluate the association of serum phosphorus with cardiac structure/function and incident heart failure. Methods and results We related serum phosphorus to echocardiographic left ventricular (LV) measurements cross-sectionally, and to incident heart failure prospectively in 3300 participants (mean age 44 years, 51% women) free of heart failure, myocardial infarction, and chronic kidney disease (estimated glomerular filtration rate [eGFR]<60 mL/min/1.73 m(2)). Cross-sectionally, serum phosphorus was related positively to LV mass, internal dimensions, and systolic dysfunction. On follow-up (mean 17.4 years), 157 individuals developed heart failure. In models adjusting for established risk factors as time-varying covariates, each mg/dL increment in serum phosphorus was associated with a 1.74-fold risk of heart failure [95% confidence intervals (CI) 1.17-2.59]. Individuals in the highest serum phosphorus quartile experienced a two-fold (95% CI 1.28-3.40) risk of heart failure compared with participants in the lowest quartile. These relations were maintained upon additional adjustment for LV mass/dimensions and systolic dysfunction. In analyses restricted to individuals with eGFR >90 mUmin/1.73 m(2), no proteinuria and serum phosphorus <4.5 mg/dL, the association of serum phosphorus with heart failure remained robust. Conclusion In our community-based sample, higher serum phosphorus was associated with greater LV mass cross-sectionally, and with an increased risk of heart failure prospectively. C1 [Dhingra, Ravi; Gona, Philimon; Benjamin, Emelia J.; Wang, Thomas J.; D'Agostino, Ralph B., Sr.; Kannel, William B.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Dhingra, Ravi] Dartmouth Hitchcock Med Ctr, Div Cardiol, Lebanon, NH 03766 USA. [Dhingra, Ravi] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gona, Philimon; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Aragam, Jayashri] Vet Affairs Hosp, W Roxbury, MA USA. [Benjamin, Emelia J.; Kannel, William B.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect EJB RSV, Boston, MA 02118 USA. [Benjamin, Emelia J.; Kannel, William B.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NIH/NHLBI [N01-HC-25195, HL080124, 2K24HL4334] FX This work was supported by the NIH/NHLBI Contract No. N01-HC-25195; HL080124, and 2K24HL4334 (Dr R.S.V.). NR 34 TC 44 Z9 46 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD AUG PY 2010 VL 12 IS 8 BP 812 EP 818 DI 10.1093/eurjhf/hfq106 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 642HR UT WOS:000281200100008 PM 20675668 ER PT J AU Shah, RV Chen-Tournoux, AA Picard, MH van Kimmenade, RRJ Januzzi, JL AF Shah, Ravi V. Chen-Tournoux, Annabel A. Picard, Michael H. van Kimmenade, Roland R. J. Januzzi, James L. TI Galectin-3, cardiac structure and function, and long-term mortality in patients with acutely decompensated heart failure SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Echocardiography; Prognosis ID EMERGENCY-DEPARTMENT PRIDE; DYSPNEA; PRO; MACROPHAGES; DYSFUNCTION; BIOMARKERS; PROGNOSIS; FIBROSIS; DISEASE AB Aims To determine the relationship between galectin-3 concentrations and cardiac structure in patients with acute dyspnoea, and to evaluate the impact of galectin-3 independent of echocardiographic measurements on long-term mortality. Methods and results One hundred and fifteen patients presenting to the emergency department with acute dyspnoea who had galectin-3 levels and detailed echocardiographic studies on admission were studied. Galectin-3 levels were associated with older age (r = 0.26, P = 0.006), lower creatinine clearance (r = -0.42, P < 0.001), and higher levels of N-terminal-proBNP (r = 0.39, P < 0.001). Higher galectin-3 levels were associated with tissue Doppler E/E(a) ratio (r = 0.35, P = 0.01), a lower right ventricular (RV) fractional area change (r = -0.19, P = 0.05), higher RV systolic pressure (r = 0.37, P < 0.001), and more severe mitral (r = 0.30, P = 0.001) or tricuspid regurgitation (r = 0.26, P = 0.005). In patients diagnosed with heart failure (HF), the association between galectin-3 and valvular regurgitation and RV systolic pressure persisted. In a multivariate Cox regression model, galectin-3 remained a significant predictor of 4-year mortality independent of echocardiographic markers of risk. Dyspnoeic patients with HF and galectin-3 levels above the median value had a 63% mortality; patients less than the median value had a 37% mortality (P = 0.003). Conclusion Among dyspnoeic patients with and without ADHF, galectin-3 concentrations are associated with echocardiographic markers of ventricular function. In patients with ADHF, a single admission galectin-3 level predicts mortality to 4 years, independent of echocardiographic markers of disease severity. C1 [Shah, Ravi V.; Chen-Tournoux, Annabel A.; Picard, Michael H.; Januzzi, James L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA 02114 USA. [van Kimmenade, Roland R. J.] Univ Hosp Maastricht, Dept Cardiol, Maastricht, Netherlands. RP Januzzi, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org RI Kimmenade, R.R.J./L-4432-2015; OI Picard, Michael/0000-0002-9264-3243 FU National Heart, Lung, and Blood Institute Heart Failure Research Network (Boston, MA, USA); Balson Scholar Fund (Boston, MA, USA); Interuniversity Cardiology Institute of the Netherlands FX This work was supported by the National Heart, Lung, and Blood Institute Heart Failure Research Network (R.V.S.; Boston, MA, USA), the Balson Scholar Fund (J.L.J.; Boston, MA, USA), and the Interuniversity Cardiology Institute of the Netherlands (R.R.J.K.). NR 18 TC 140 Z9 146 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD AUG PY 2010 VL 12 IS 8 BP 826 EP 832 DI 10.1093/eurjhf/hfq091 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 642HR UT WOS:000281200100010 PM 20525986 ER PT J AU Bergen, SE Maher, BS Fanous, AH Kendler, KS AF Bergen, Sarah E. Maher, Brion S. Fanous, Ayman H. Kendler, Kenneth S. TI Detection of susceptibility genes as modifiers due to subgroup differences in complex disease SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE modifier; simulation; subtyping; complex disease ID GENOME-WIDE ASSOCIATION; SPINOCEREBELLAR ATAXIA TYPE-2; CLINICAL-FEATURES; CYSTIC-FIBROSIS; DYSBINDIN GENE; SCHIZOPHRENIA; GENOTYPE; SYMPTOMS; AGE; HETEROGENEITY AB Complex diseases invariably involve multiple genes and often exhibit variable symptom profiles. The extent to which disease symptoms, course, and severity differ between affected individuals may result from underlying genetic heterogeneity. Genes with modifier effects may or may not also influence disease susceptibility. In this study, we have simulated data in which a subset of cases differ by some effect size (ES) on a quantitative trait and are also enriched for a risk allele. Power to detect this 'pseudo-modifier' gene in case-only and case-control designs was explored blind to case substructure. Simulations involved 1000 iterations and calculations for 80% power at P<0.01 while varying the risk allele frequency (RAF), sample size (SS), ES, odds ratio (OR), and proportions of the case subgroups. With realistic values for the RAF (0.20), SS (3000) and ES (1), an OR of 1.7 is necessary to detect a pseudo-modifier gene. Unequal numbers of subjects in the case groups result in little decrement in power until the group enriched for the risk allele is <30% or >70% of the total case population. In practice, greater numbers of subjects and selection of a quantitative trait with a large range will provide researchers with greater power to detect a pseudo-modifier gene. However, even under ideal conditions, studies involving alleles with low frequencies or low ORs are usually underpowered for detection of a modifier or susceptibility gene. This may explain some of the inconsistent association results for many candidate gene studies of complex diseases. European Journal of Human Genetics (2010) 18, 960-964; doi:10.1038/ejhg.2010.39; published online 31 March 2010 C1 [Bergen, Sarah E.; Maher, Brion S.; Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA. [Bergen, Sarah E.; Maher, Brion S.; Fanous, Ayman H.; Kendler, Kenneth S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Maher, Brion S.; Fanous, Ayman H.; Kendler, Kenneth S.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Fanous, Ayman H.] Washington VA Med Ctr, Washington, DC USA. [Fanous, Ayman H.] Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20007 USA. RP Bergen, SE (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM sbergen@gmail.com RI Maher, Brion/F-9185-2010; Bergen, Sarah/I-8313-2012; OI Bergen, Sarah/0000-0002-5888-0034 FU NIH [MH41953, DE016632, MH20030] FX This work was funded by NIH grants MH41953 to KSK, DE016632 to BSM, training grant MH20030 supporting SEB, and a VA Merit Review Program grant to AHF. NR 28 TC 4 Z9 4 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD AUG PY 2010 VL 18 IS 8 BP 960 EP 964 DI 10.1038/ejhg.2010.39 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 628TO UT WOS:000280145100016 PM 20354561 ER PT J AU Tedeschini, E Fava, M Goodness, TM Papakostas, GI AF Tedeschini, Enrico Fava, Maurizio Goodness, Tracie M. Papakostas, George I. TI Relationship between probability of receiving placebo and probability of prematurely discontinuing treatment in double-blind, randomized clinical trials for MDD: A meta-analysis SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Antidepressant; Placebo; Discontinuation; Major; Depressive; Disorder; Adults ID MAJOR DEPRESSION; DIAGNOSTIC CRITERIA; RATING-SCALE; RUN-IN; DISORDERS; EFFICACY AB An increased likelihood of receiving placebo in randomized clinical trials has been found to predict greater chances of trial success. However, patients who are less likely to receive active therapy (and more likely to receive placebo) may be at increased risk of attrition which, in turn, can limit the statistical power of a study. Therefore, in the present work, we sought to investigate the relationship between the probability of receiving placebo and the likelihood of prematurely discontinuing treatment. Medline/Pubmed publication databases were searched for RCT in MDD. A meta-regression established that the likelihood of receiving placebo did not predict either antidepressant discontinuation rates, placebo-discontinuation rates or the risk ratio of discontinuing antidepressants versus placebo. An increased likelihood of receiving placebo did not inflate discontinuation rates which did not influence the degree of antidepressant-placebo "separation". (C) 2010 Elsevier B.V. and ECNP. All rights reserved. C1 [Tedeschini, Enrico; Fava, Maurizio; Goodness, Tracie M.; Papakostas, George I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. [Tedeschini, Enrico] Univ Modena & Reggio Emilia, Dept Psychiat, Modena, Italy. RP Tedeschini, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, 50 Staniford St, Boston, MA 02114 USA. EM etedeschini@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Bristol-Myers Squibb Company; Forest Pharmaceuticals; National Institute of Mental; Abbott Laboratories; Alkermes; Aspect Medical Systems; Astra-Zeneca; Bio Research; Brain Cells, Inc.; Cephalon; Clinical Trial Solutions; Eli Lilly Et Company; Forest Pharmaceuticals Inc.; Ganeden; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; NARSAD; NCCAM; NIDA; NIMH; Novartis; Organon Inc. FX Dr. Papakostas has served as a consultant for Astra-Zeneca PLC, Bristol-Myers Squibb Company, Eli Lilly Co., GlaxoSmithKline, Evotec AG, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer Inc., Pierre Fabre Laboratories, Shire Pharmaceuticals, and Wyeth, Inc.; has received honoraria from Astra-Zeneca PLC, Bristol-Myers Squibb Company, Eli Lilly Co., Evotec AG, GlaxoSmithKline, Inflabloc Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, Otsuka Pharmaceuticals, PAMLAB LLC, Pfizer, Pierre Fabre Laboratories, Shire Pharmaceuticals, Titan Pharmaceuticals, and Wyeth Inc.; has received research support from Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental; and has served on the speaker's bureau for Bristol-Myers Squibb Co and Pfizer, Inc.; Dr. Fava has served as an advisor/consultant for Abbott Laboratories, Amarin, Aspect Medical Systems, Astra-Zeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, Inc, Biovail Pharmaceuticals, Inc., Brain Cells, Inc, BristolMyers Squibb Company, Cephalon, Clinical Trials Solutions, CNS Response, Compel lis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly a Company, EPIX Pharmaceuticals, Fabre-Kramer, Pharmaceuticals, Inc., Forest Pharmaceuticals Inc., GlaxoSmithKline, Grunenthal GmBH Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante Inc. Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon Inc., PamLab, LLC, Pfizer Inc, PharmaStar, Pharmavite, Precision Human Biolaboratory, Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay Pharmaceuticals, Inc., Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, Transcept Pharmaceuticals, Vanda Pharmaceuticals In Wyeth-Ayerst Laboratories; has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, Astra-Zeneca, Bio Research, Brain Cells, Inc., Bristol-Myers Squibb Company, Cephalon, Clinical Trial Solutions, Eli Lilly Et Company, Forest Pharmaceuticals Inc., Ganeden, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, NARSAD, NCCAM, NIDA, NIMH, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc, Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Inc., Synthelabo, Wyeth-Ayerst Laboratories; has served as a speaker for Advanced Meeting Partners, American Psychiatric Association, Astra-Zeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb Company, Cephalon, Eli Lilly Et Company, Forest Pharmaceuticals Inc., GlaxoSmithKline, Imedex, Novartis, Organon Inc., Pfizer Inc, PharmaStar, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed-Elsevier, UBC, Wyeth-Ayerst Laboratories; has equity Holdings in Compel lis; and has patent applications for SPCD and for a combination of azapirones and bupropion in MDD, copyright royalties for the MGH CPFQ_, SFI, ATRQ, DESS, and SAFER. NR 24 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 IS 8 BP 562 EP 567 DI 10.1016/j.euroneuro.2010.02.004 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 630FL UT WOS:000280258400005 PM 20219330 ER PT J AU Biederman, J Wozniak, J AF Biederman, J. Wozniak, J. TI The long term course of pediatric bipolar disorder: a five year longitudinal follow up study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Biederman, J.; Wozniak, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S611 EP S612 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800822 ER PT J AU Biederman, J Petty, C Monuteaux, M Faraone, S AF Biederman, J. Petty, C. Monuteaux, M. Faraone, S. TI Psychiatric outcomes of girls with ADHD grown up: a controlled 11-year follow-up study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Biederman, J.; Petty, C.; Monuteaux, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faraone, S.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S612 EP S613 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800823 ER PT J AU Biederman, J Fried, R Petty, C Faraone, S AF Biederman, J. Fried, R. Petty, C. Faraone, S. TI Examination of the effects of stimulant treatment across the adult lifecycle of adults with ADHD: a controlled study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Biederman, J.; Fried, R.; Petty, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faraone, S.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Faraone, S.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S329 EP S329 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800336 ER PT J AU Biederman, J Mick, E AF Biederman, J. Mick, E. TI A randomized, three phase 34 week double-blind long-term efficacy study of extended-release methylphenidate in adults with ADHD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Biederman, J.; Mick, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S329 EP S330 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800337 ER PT J AU Herbert, MR AF Herbert, M. R. TI Environment and vulnerable physiology in autism SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol ID SPECTRUM C1 [Herbert, M. R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, TRANSCEND, Charlestown, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S177 EP S177 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800046 ER PT J AU Marder, S Buchanan, RW AF Marder, S. Buchanan, R. W. TI NIMH/FDA guidelines for clinical trials for cognition in schizophrenia: how much have we advanced? SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Marder, S.] W Los Angeles VA Hlth Care Ctr, Los Angeles, CA USA. [Buchanan, R. W.] Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. 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 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S194 EP S194 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800091 ER PT J AU Tedeschini, E Levkovitz, Y Papakostas, G AF Tedeschini, E. Levkovitz, Y. Papakostas, G. TI Antidepressants for late-life depression: a meta analysis of placebo-controlled randomized trials SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 23rd Congress Meeting of European-College-of-Neuropsychopharmacology CY AUG 28-SEP 01, 2010 CL Amsterdam, NETHERLANDS SP European Coll Neuropsychopharmacol C1 [Tedeschini, E.] Univ Modena & Reggio Emilia, Modena, Italy. [Levkovitz, Y.] Emot Cognit Res Ctr, Shalvata Mental Hlth Ctr, Tel Aviv, Israel. [Papakostas, G.] Massachusetts Gen Hosp, Psychiat DCRP, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2010 VL 20 SU 3 BP S382 EP S383 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 673UB UT WOS:000283687800428 ER PT J AU Killeen, RP Arnous, S Martos, R Abbara, S Quinn, M Dodd, JD AF Killeen, Ronan P. Arnous, Samer Martos, Ramon Abbara, Suhny Quinn, Martin Dodd, Jonathan D. TI Chronic mitral regurgitation detected on cardiac MDCT: differentiation between functional and valvular aetiologies SO EUROPEAN RADIOLOGY LA English DT Article DE Cardiomyopathy; Dilated/complications; Mitral valve/anatomy; Mitral valve insufficiency/aetiology; Computed tomography; Coronary artery disease ID AMERICAN-HEART-ASSOCIATION; 3-DIMENSIONAL ECHOCARDIOGRAPHY; OUTCOME IMPLICATIONS; WALL-MOTION; DISEASE; PREVALENCE; VALVE; CT; RECONSTRUCTION; MANAGEMENT AB To determine whether cardiac computed tomography (MDCT) can differentiate between functional and valvular aetiologies of chronic mitral regurgitation (MR) compared with echocardiography (TTE). Twenty-seven patients with functional or valvular MR diagnosed by TTE and 19 controls prospectively underwent cardiac MDCT. The morphological appearance of the mitral valve (MV) leaflets, MV geometry, MV leaflet angle, left ventricular (LV) sphericity and global/regional wall motion were analysed. The coronary arteries were evaluated for obstructive atherosclerosis. All control and MR cases were correctly identified by MDCT. Significant differences were detected between valvular and control groups for anterior leaflet length (30 +/- 7 mm vs. 22 +/- 4 mm, P < 0.02) and thickness (3.0 +/- 1 mm vs. 2.2 +/- 1 mm, P < 0.01). High-grade coronary stenosis was detected in all patients with functional MR compared with no controls (P < 0.001). Significant differences in those with/without MV prolapse were detected in MV tent area (-1.0 +/- 0.6 mm vs. 1.3 +/- 0.9 mm, P < 0.0001) and MV tent height (-0.7 +/- 0.3 mm vs. 0.8 +/- 0.8 mm, P < 0.0001). Posterior leaflet angle was significantly greater for functional MR (37.9 +/- 19.1A degrees vs. 22.9 A +/- 14A degrees, P < 0.018) and less for valvular MR (0.6 A +/- 35.5A degrees vs. 22.9 A +/- 14A degrees, P < 0.017). Sensitivity, specificity, and positive and negative predictive values of MDCT were 100%, 95%, 96% and 100%. Cardiac MDCT allows the differentiation between functional and valvular causes of MR. C1 [Killeen, Ronan P.; Dodd, Jonathan D.] St Vincents Univ Hosp, Dept Radiol, Dublin 4, Ireland. [Arnous, Samer; Martos, Ramon; Quinn, Martin] St Vincents Univ Hosp, Dept Cardiol, Dublin 4, Ireland. [Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Dodd, JD (reprint author), St Vincents Univ Hosp, Dept Radiol, Elm Pk 4, Dublin 4, Ireland. EM j.dodd@st-vincents.ie NR 30 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD AUG PY 2010 VL 20 IS 8 BP 1886 EP 1895 DI 10.1007/s00330-010-1760-4 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 622IU UT WOS:000279656400011 PM 20309557 ER PT J AU Abujudeh, HH Boland, GW Kaewlai, R Rabiner, P Halpern, EF Gazelle, GS Thrall, JH AF Abujudeh, Hani H. Boland, Giles W. Kaewlai, Rathachai Rabiner, Pavel Halpern, Elkarn F. Gazelle, G. Scott Thrall, James H. TI Abdominal and pelvic computed tomography (CT) interpretation: discrepancy rates among experienced radiologists SO EUROPEAN RADIOLOGY LA English DT Article DE Peer-review system; Radiological error; Discrepancy rate; Computed tomography; Abdomen; Pelvis ID DIAGNOSTIC-PROCEDURES; ERROR; ACCURACY AB To assess the discrepancy rate for the interpretation of abdominal and pelvic computed tomography (CT) examinations among experienced radiologists. Ninety abdominal and pelvic CT examinations reported by three experienced radiologists who specialize in abdominal imaging were randomly selected from the radiological database. The same radiologists, blinded to previous interpretation, were asked to re-interpret 60 examinations: 30 of their previous interpretations and 30 interpreted by others. All reports were assessed for the degree of discrepancy between initial and repeat interpretations according to a three-level scoring system: no discrepancy, minor, or major discrepancy. Inter- and intrareader discrepancy rates and causes were evaluated. CT examinations included in the investigation were performed on 90 patients (43 men, mean age 59 years, SD 14, range 19-88) for the following indications: follow-up/evaluation of malignancy (69/90, 77%), pancreatitis (5/90, 6%), urinary tract stone (4/90, 4%) or other (12/90, 13%). Interobserver and intraobserver major discrepancy rates were 26 and 32%, respectively. Major discrepancies were due to missed findings, different opinions regarding interval change of clinically significant findings, and the presence of recommendation. Major discrepancy of between 26 and 32% was observed in the interpretation of abdominal and pelvic CT examinations. C1 [Abujudeh, Hani H.; Boland, Giles W.; Kaewlai, Rathachai; Rabiner, Pavel; Halpern, Elkarn F.; Gazelle, G. Scott; Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Abujudeh, Hani H.; Boland, Giles W.; Kaewlai, Rathachai; Rabiner, Pavel; Halpern, Elkarn F.; Gazelle, G. Scott; Thrall, James H.] Harvard Univ, Sch Med, Boston, MA USA. [Halpern, Elkarn F.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Abujudeh, HH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND-220, Boston, MA 02114 USA. EM habujudeh@partners.org OI Kaewlai, Rathachai/0000-0002-0650-9380 NR 17 TC 21 Z9 21 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD AUG PY 2010 VL 20 IS 8 BP 1952 EP 1957 DI 10.1007/s00330-010-1763-1 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 622IU UT WOS:000279656400018 PM 20336300 ER PT J AU Geisler, BP AF Geisler, Benjamin P. TI Treating anemia in heart failure patients: a review of erythropoiesis-stimulating agents SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE carbamylated erythropoietin; continuous erythropoietin receptor activator; erythropoietin; heart failure; recombinant ID CHRONIC KIDNEY-DISEASE; QUALITY-OF-LIFE; EPOETIN-ALPHA; RENAL-FUNCTION; HEMOGLOBIN CONCENTRATION; HEMODIALYSIS-PATIENTS; RESOURCE UTILIZATION; SECONDARY ANALYSIS; DIALYSIS PATIENTS; CONTROLLED-TRIAL AB Importance of the field: Prevalence of chronic heart failure (CHF) is increasing, and despite improvements in the past decade the prognosis in terms of mortality and health-related quality of life remains poor. Anemia is often found concomitantly in CHF patients. Areas covered in this review: Erythropoiesis-stimulating agents (ESAs) are a new treatment option for these anemic CHF patients, promising to decrease mortality and hospitalizations, and increase health-related quality of life. What the reader will gain: CHF epidemiology is briefly dicussed. Currently available clinical efficacy and safety data are critically appraised. Health care utilization by CHF patients, particularly hospitalizations, are reviewed in order predict cost-effectiveness of ESAs. Take home messages: The efficacy for the most pertinent endpoints has not been proven by a pivotal trial or a meta-analysis free of bias, and there might be increased cardiovascular events and cancer incidence rates above a currently unknown target value or with multiple doses. However, subgroups should be identified in which ESAs might prove to be more efficacious and as safe as usual care and either cost-saving or cost-effective. Nevertheless, depending on the subgroup, the budget effect for payors might be dramatic due to the large number of CHF patients. C1 [Geisler, Benjamin P.] Massachusetts Gen Hosp, Inst Technol Assessment, Somerville, MA 02143 USA. [Geisler, Benjamin P.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Geisler, BP (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 18 Pleasant Ave, Somerville, MA 02143 USA. EM ben.geisler@gmail.com RI Geisler, Benjamin/A-9244-2010 OI Geisler, Benjamin/0000-0003-1704-6067 FU Amgen, Inc. FX The author was a subcontractor for a research project that received unrestricted support from Amgen, Inc., a manufacturer of ESAs. The author also received direct support from Amgen, Inc., a manufacturer of ESAs to present the outcomes of that project at a conference. NR 82 TC 2 Z9 2 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD AUG PY 2010 VL 10 IS 8 BP 1209 EP 1216 DI 10.1517/14712598.2010.500282 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 629JB UT WOS:000280191000004 PM 20557272 ER PT J AU Ho, L Pasinetti, GM AF Ho, Lap Pasinetti, Giulio Maria TI Polyphenolic compounds for treating neurodegenerative disorders involving protein misfolding SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE Alzheimer's disease; beta-amyloid; grape seed polyphenolic extract; Huntington's disease; neurodegenerative disorders; Parkinson's disease; polyphenols; tau; tauopathy ID ALZHEIMER TRANSGENIC MICE; PAIRED HELICAL FILAMENTS; ALPHA-SYNUCLEIN; IN-VITRO; GRAPE SEED; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; TAU PATHOLOGY; AGGREGATION; TAUOPATHIES AB A diverse group of neurodegenerative diseases are characterized by progressive, age-dependent intracellular formation of misfolded protein aggregates. These include Alzheimer's disease, Huntington's disease, Parkinson's disease and a number of tau-mediated disorders. There is no effective treatment for any of these disorders; currently approved interventions are designed to treat disease symptoms and generally lead to modest modulation of clinical symptoms. None are known to mitigate underlying neuropathologic mechanisms and, thus, it is not unexpected that existing treatments appear ineffective in modulating disease progression. We note that these neurodegenerative disorders all share a common mechanistic theme in that depositions of misfolded protein in the brain is a key molecular feature underlying disease onset and/or progression. While previous studies have identified a number of drugs and nutraceuticals capable of interfering with the formation and/or stability of misfolded protein aggregates, none have been demonstrated to be effective in vivo for treating any of the neurodegenerative disorders. We hereby review accumulating evidence that a select nutraceutical grape-seed polyphenolic extract (GSPE) is effective in vitro and in vivo in mitigating certain misfolded protein-mediated neuropathologic and clinical phenotypes. We will also review evidence implicating bioavailability of GSPE components in the brain and the tolerability as well as safety of GSPE in animal models and in humans. Collectively, available information supports continued development of the GSPE for treating a variety of neurodegenerative disorders involving misfolded protein-mediated neuropathologic mechanisms. C1 [Ho, Lap; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Ctr Excellence Novel Approaches Neurodiagnost & N, Ctr Excellence Res Complementary & Alternat Med A, Dept Neurol,Brain Inst, New York, NY 10029 USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Ctr Excellence Novel Approaches Neurodiagnost & N, Ctr Excellence Res Complementary & Alternat Med A, Dept Neurol,Brain Inst, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu NR 45 TC 13 Z9 13 U1 3 U2 14 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD AUG PY 2010 VL 7 IS 4 BP 579 EP 589 DI 10.1586/EPR.10.69 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 637BH UT WOS:000280788800015 PM 20653511 ER PT J AU Theodoropoulou, S Kolovou, PE Morizane, Y Kayama, M Nicolaou, F Miller, JW Gragoudas, E Ksander, BR Vavvas, DG AF Theodoropoulou, Sofia Kolovou, Paraskevi E. Morizane, Yuki Kayama, Maki Nicolaou, Fotini Miller, Joan W. Gragoudas, Evangelos Ksander, Bruce R. Vavvas, Demetrios G. TI Retinoblastoma cells are inhibited by aminoimidazole carboxamide ribonucleotide (AICAR) partially through activation of AMP-dependent kinase SO FASEB JOURNAL LA English DT Article DE cancer; energy; metabolism; eye; intraocular tumors ID RIBOSIDE INDUCES APOPTOSIS; PROTEIN-KINASE; BILATERAL RETINOBLASTOMA; ENERGY STATUS; KEY SENSOR; CANCER; GROWTH; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE-1-BETA-D-RIBOFURANOSIDE; CHEMOREDUCTION; CHEMOTHERAPY AB 5-Aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), an analog of AMP, is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. We studied the effects of AICAR on the growth of retinoblastoma cell lines (Y79, WERI, and RB143). AICAR inhibited Rb cell growth, induced apoptosis and S-phase cell cycle arrest, and led to activation of AMPK. These effects were abolished by treatment with dypiridamole, an inhibitor that blocks entrance of AICAR into cells. Treatment with the adenosine kinase inhibitor 5-iodotubericidin to inhibit the conversion of AICAR to ZMP (the direct activator of AMPK) reversed most of the growth-inhibiting effects of AICAR, indicating that some of the antiproliferative effects of AICAR are mediated through AMPK activation. In addition, AICAR treatment was associated with inhibition of the mammalian target of rapamycin pathway, decreased phosphorylation of ribosomal protein-S6 and 4E-BP1, down-regulation of cyclins A and E, and decreased expression of p21. Our results indicate that AICAR-induced activation of AMPK inhibits retinoblastoma cell growth. This is one of the first descriptions of a nonchemotherapeutic drug with low toxicity that may be effective in treating Rb patients.-Theodoropoulou, S., Kolovou, P. E., Morizane, Y., Kayama, M., Nicolaou, F., Miller, J. W., Gragoudas, E., Ksander, B. R., Vavvas, D. G. Retinoblastoma cells are inhibited by aminoimidazole carboxamide ribonucleotide (AICAR) partially through activation of AMP-dependent kinase. FASEB J. 24, 2620-2630 (2010). www.fasebj.org C1 [Theodoropoulou, Sofia; Morizane, Yuki; Kayama, Maki; Miller, Joan W.; Gragoudas, Evangelos; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab,Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. [Kolovou, Paraskevi E.; Ksander, Bruce R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. [Nicolaou, Fotini] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Labs, Boston, MA 02114 USA. RP Vavvas, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab,Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. EM demetrios_vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 FU Onassis Foundation; Massachusetts Lions Eye Research Fund; Research to Prevent Blindness; U.S. National Institutes of Health [NIH EY009294] FX D.G.V. was supported by an Onassis Foundation Scholars grant, the Massachusetts Lions Eye Research Fund, and Research to Prevent Blindness. B.R.K. was supported by U.S. National Institutes of Health grant NIH EY009294. NR 44 TC 21 Z9 22 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD AUG PY 2010 VL 24 IS 8 BP 2620 EP 2630 DI 10.1096/fj.09-152546 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 690LD UT WOS:000285005400004 PM 20371623 ER PT J AU Anelli, V Gault, CR Snider, AJ Obeid, LM AF Anelli, Viviana Gault, Christopher R. Snider, Ashley J. Obeid, Lina M. TI Role of sphingosine kinase-1 in paracrine/transcellular angiogenesis and lymphangiogenesis in vitro SO FASEB JOURNAL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; SIGNALING PATHWAYS; MOLECULAR-CLONING; FUNCTIONAL-CHARACTERIZATION; EXTRACELLULAR RELEASE; MASS-SPECTROMETRY; POOR SURVIVAL; G-PROTEIN; VEGF-C; 1-PHOSPHATE AB Sphingosine-1-phosphate (S1P) is an important bioactive sphingolipid involved in angiogenesis and lymphangiogenesis, 2 important processes that influence the growth, survival, and spread of tumors. S1P acts as an extracellular mediator through binding to 5 highly specific S1P receptors, S1P(1-5). Sphingosine kinase-1 (SK1), one of 2 known sphingosine kinase enzymes responsible for S1P production, appears to be overexpressed in many tumors. Although a role for S1P in angiogenesis and lymphangiogenesis has been established, it is unclear whether S1P secreted from cancer cells has a paracrine function in a tumor environment. Here we investigated whether modulation of cellular SK1 could initiate a paracrine angiogenic and lymphangiogenic switch. We found that SK1 overexpression in HEK cells or its down-regulation in glioma or breast cancer cells modulated extracellular S1P levels accordingly, which in turn increased or decreased both migration and tube formation in cocultured vascular or lymphatic endothelial cells. In contrast, down-regulation of sphingosine kinase 2 in both glioma and breast cancer cells had no appreciable effect on cellular or secreted S1P levels. In addition, vascular endothelial growth factors VEGF and VEGF-C down-regulation in cancer cells appeared insufficient to block the angiogenic and lymphangiogenic switch triggered by these cells. Moreover, S1P initiated endothelial cell sprouting in 3-dimensional collagen matrices, which is representative of a multistep angiogenic process. Our data collectively demonstrate for the first time that SK1 plays an essential role in regulating in vitro paracrine angiogenesis and lymphangiogenesis.-Anelli, V., Gault, C. R., Snider, A.J., Obeid, L. M. Role of sphingosine kinase-1 in paracrine/transcellular angiogenesis and lymphangiogenesis in vitro. FASEB J. 24, 2727-2738 (2010). www.fasebj.org C1 [Obeid, Lina M.] Med Univ S Carolina, Div Gen Internal Med Geriatr, Dept Med, Charleston, SC 29425 USA. [Anelli, Viviana; Obeid, Lina M.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Anelli, Viviana] Univ Milan, Dept Med Chem Biochem & Biotechnol, Milan, Italy. [Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Div Gen Internal Med Geriatr, Dept Med, MSC 779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU National Institutes of Health [NIH/NIGMS GM062887, NIH/NCI CA097132, NIH/P20 RR17677]; Hollings Cancer Center [P30-CA-56036] FX The authors thank Kathy Wiita-Fisk for administrative assistance. The authors also thank the Lipidomics Core at the Medical University of South Carolina. Grant support came from National Institutes of Health grants NIH/NIGMS GM062887 (L.M.O.), NIH/NCI CA097132 (L.M.O.), NIH/P20 RR17677 for the Centers of Biomedical Research Excellence (COBRE) Lipidomics Core, and Hollings Cancer Center core grant P30-CA-56036 for the Microscopy Core. NR 39 TC 39 Z9 39 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 2010 VL 24 IS 8 BP 2727 EP 2738 DI 10.1096/fj.09-150540 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 690LD UT WOS:000285005400014 PM 20335228 ER PT J AU Reindollar, RH Regan, MM Neumann, PJ Levine, BS Thornton, KL Alper, MM Goldman, MB AF Reindollar, Richard H. Regan, Meredith M. Neumann, Peter J. Levine, Bat-Sheva Thornton, Kim L. Alper, Michael M. Goldman, Marlene B. TI A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial SO FERTILITY AND STERILITY LA English DT Article DE Unexplained infertility; FASTT Trial; intrauterine insemination; in vitro fertilization ID IN-VITRO FERTILIZATION; HUMAN CHORIONIC-GONADOTROPIN; MULTIPLE PREGNANCY RATE; INTRAUTERINE INSEMINATION; CLOMIPHENE CITRATE; COST; REPRODUCTION; FECUNDITY; EFFICACY; CYCLES AB Objective: To determine the value of gonadotropin/ intrauterine insemination (FSH/IUI) therapy for infertile women aged 21-39 years. Design: Randomized controlled trial. Setting: Academic medical center associated with a private infertility center. Patient(s): Couples with unexplained infertility. Intervention(s): Couples were randomized to receive either conventional treatment (n = 247) with three cycles of clomiphene citrate (CC)/IUI, three cycles of FSH/IUI, and up to six cycles of IVF or an accelerated treatment (n 256) that omitted the three cycles of FSH/IUI. Main Outcome Measure(s): The time it took to establish a pregnancy that led to a live birth and cost-effectiveness, defined as the ratio of the sum of all health insurance charges between randomization and delivery divided by the number of couples delivering at least one live-born baby. Result(s): An increased rate of pregnancy was observed in the accelerated arm (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.00-1.56) compared with the conventional arm. Median time to pregnancy was 8 and 11 months in the accelerated and conventional arms, respectively. Per cycle pregnancy rates for CC/IUI, FSH/IUI, and IVF were 7.6%, 9.8%, and 30.7%, respectively. Average charges per delivery were $9,800 lower (95% CI, $25,100 lower to $3,900 higher) in the accelerated arm compared to conventional treatment. The observed incremental difference was a savings of $2,624 per couple for accelerated treatment and 0.06 more deliveries. Conclusion(s): A randomized clinical trial demonstrated that FSH/IUI treatment was of no added value. (Fertil Steril (R) 2010; 94: 888-99. (c) 2010 by American Society for Reproductive Medicine.) C1 [Reindollar, Richard H.; Goldman, Marlene B.] Dartmouth Hitchcock Med Ctr, Dept Obstet & Gynecol, Dartmouth Med Sch, Lebanon, NH 03756 USA. [Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Neumann, Peter J.; Levine, Bat-Sheva] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Neumann, Peter J.; Levine, Bat-Sheva] Tufts Med Ctr, Ctr Evaluat Value & Risk Hlth, Boston, MA USA. [Thornton, Kim L.; Alper, Michael M.] Beth Israel Deaconess Med Ctr, Div Reprod Endocrinol & Infertil, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02215 USA. [Goldman, Marlene B.] Dartmouth Hitchcock Med Ctr, Dept Community & Family Med, Dartmouth Med Sch, Lebanon, NH 03756 USA. RP Reindollar, RH (reprint author), Dartmouth Hitchcock Med Ctr, Dept Obstet & Gynecol, Dartmouth Med Sch, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Richard.H.Reindollar@Hitchcock.org FU Ferring; Organon; Serono; Serono and General Electric,; Novo Nordisk; Duramed; National Institute of Child Health and Human Development; National Institutes of Health, Bethesda, Maryland [R01 HD38561] FX R.H.R. reports receiving fellowship training funds and lecture fees from Ferring, Organon, and Serono before 2005. M.M.R. has nothing to disclose. P.J.N. reports receiving grant support from Elan Pharmaceuticals and Johnson & Johnson, receiving consultant fees from Serono and General Electric, and serving on advisory boards for Merck, Schering Plough, and Abbott; B-S.L. reports receiving an educational grant from Novo Nordisk. K.L.T. reports receiving fellowship training support from Ferring, research grant support from Duramed, Organon, and Serono, consulting fees from Organon, and lecture fees from Organon and Serono. M.M.A. reports receiving unrestricted research grants from Serono and Organon, consulting fees from Serono, and lecture fees from Ferring, Organon, and Serono. M.B.G. has nothing to disclose.; Supported by a grant from the National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (R01 HD38561). The National Institute of Child Health and Human Development had no role in the design or conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 26 TC 74 Z9 74 U1 2 U2 10 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 AUG PY 2010 VL 94 IS 3 BP 888 EP 899 DI 10.1016/j.fertnstert.2009.04.022 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 632FX UT WOS:000280407900012 PM 19531445 ER PT J AU Tanrikut, C Feldman, AS Altemus, M Paduch, DA Schlegel, PN AF Tanrikut, Cigdem Feldman, Adam S. Altemus, Margaret Paduch, Darius A. Schlegel, Peter N. TI Adverse effect of paroxetine on sperm SO FERTILITY AND STERILITY LA English DT Article DE Male infertility; semen analysis; antidepressants; sperm; DNA fragmentation; erectile dysfunction; ejaculation; body mass index ID CHROMATIN-STRUCTURE ASSAY; IN-VITRO FERTILIZATION; BODY-MASS INDEX; DOUBLE-BLIND; DNA-DAMAGE; ANTIDEPRESSANTS; EJACULATION; PREGNANCY; MEN; FRAGMENTATION AB Objective: To assess the effects of a selective serotonin reuptake inhibitor on semen parameters. Design: Prospective study. Setting: Academic medical center. Patient(s): Thirty-five healthy male volunteers, 18-65 years old. Intervention(s): Paroxetine administration for 5 weeks. Main Outcome Measure(s): Serum hormone levels, semen analyses, percent sperm DNA fragmentation, and questionnaire assessment of sexual function assessed before, during, and 1 month after drug administration. Result(s): Mean sperm DNA fragmentation was significantly higher for men while on paroxetine (30.3%) versus baseline (13.8%). Before paroxetine, 9.7% of patients had a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) score >= 30% compared with 50% at week 4 of treatment. The odds ratio (OR) of having abnormal DNA fragmentation while taking paroxetine was 9.33 (95% confidence interval, 2.3-37.9). Multivariate logistic regression correcting for age and body mass index confirmed this correlation (OR, 11.12). Up to 35% of men noted significant changes in erectile function and up to 47% of men reported ejaculatory difficulties on medication. Recovery to near-normal sexual function was noted after stopping treatment. Standard semen parameters were not significantly altered during paroxetine treatment. Conclusion(s): In men with normal semen parameters, paroxetine induced abnormal sperm DNA fragmentation in a significant proportion of subjects, without a measurable effect on semen parameters. The fertility potential of a substantial number of men on paroxetine may be adversely affected by these changes in sperm DNA integrity. (Fertil Steril (R) 2010; 94: 1021-6. (C) 2010 by American Society for Reproductive Medicine.) C1 [Tanrikut, Cigdem; Paduch, Darius A.; Schlegel, Peter N.] Cornell Univ, Weill Med Coll, Dept Urol, James Buchanan Brady Fdn,Cornell Reprod Med Inst, New York, NY 10021 USA. [Tanrikut, Cigdem; Feldman, Adam S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Altemus, Margaret] Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA. RP Schlegel, PN (reprint author), Cornell Univ, Weill Med Coll, Dept Urol, James Buchanan Brady Fdn,Cornell Reprod Med Inst, 525 E 68th St,Starr 900, New York, NY 10021 USA. EM pnschleg@med.cornell.edu FU New York Community Trust; Brady Urology Foundation FX Supported by the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and the Brady Urology Foundation. NR 28 TC 50 Z9 52 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 AUG PY 2010 VL 94 IS 3 BP 1021 EP 1026 DI 10.1016/j.fertnstert.2009.04.039 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 632FX UT WOS:000280407900029 PM 19515367 ER PT J AU Souter, I Baltagi, LM Toth, TL Petrozza, JC AF Souter, Irene Baltagi, Lina M. Toth, Thomas L. Petrozza, John C. TI Prevalence of hyperprolactinemia and abnormal magnetic resonance imaging findings in a population with infertility SO FERTILITY AND STERILITY LA English DT Editorial Material DE Hyperprolactinemia; infertility; pituitary MRI; microadenoma ID SERUM PROLACTIN; PITUITARY; MICROADENOMAS; HYPOGONADISM; GALACTORRHEA; TOMOGRAPHY; AMENORRHEA; PREGNANCY; DIAGNOSIS; WOMEN AB Hyperprolactinemia is rare among asymptomatic patients with infertility. Its prevalence and the mean PRL levels did not differ with [1] the infertility diagnosis, [2] the presence or absence of menstrual irregularities, or [3] the severity of menstrual dysregulation. Abnormal magnetic resonance imaging findings, though, are not uncommon among women with hyperprolactinemia despite the lack of symptoms and the mild PRL elevations. (Fertil Steril (R) 2010;94:1159-62. (C)2010 by American Society for Reproductive Medicine.) C1 [Souter, Irene] Harvard Univ, Div Reprod Endocrinol & Infertil, Massachusetts Gen Hosp, Dept Obstet & Gynecol,Sch Med,Fertil Ctr, Boston, MA 02114 USA. RP Souter, I (reprint author), Harvard Univ, Div Reprod Endocrinol & Infertil, Massachusetts Gen Hosp, Dept Obstet & Gynecol,Sch Med,Fertil Ctr, 55 Fruit St Yawkey 10A, Boston, MA 02114 USA. EM isouter@partners.org NR 23 TC 13 Z9 16 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 AUG PY 2010 VL 94 IS 3 BP 1159 EP 1162 DI 10.1016/j.fertnstert.2009.12.017 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 632FX UT WOS:000280407900066 PM 20116788 ER PT J AU Rosenzweig, TM Hartman, S MacKenzie, E AF Rosenzweig, Tamara M. Hartman, Sarah MacKenzie, Elizabeth TI Disease-modifying therapy in adult relapsing-remitting multiple sclerosis SO FORMULARY LA English DT Article ID TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; PLACEBO-CONTROLLED TRIAL; ACADEMY-OF-NEUROLOGY; WEEKLY INTERFERON BETA-1A; DOUBLE-BLIND; GLATIRAMER ACETATE; IMMUNOMODULATORY TREATMENTS; DIAGNOSTIC-CRITERIA; COST-EFFECTIVENESS; OPEN-LABEL AB Multiple sclerosis (MS) is a significant cause of disability among young adults, more commonly women, and usually strikes patients in the prime of their lives. Despite recent therapeutic advancements, MS remains an incurable, chronic illness. Clinical evidence supports the role of disease-modifying therapy (DMT) early in the disease course to reduce the number of acute attacks, delay disease progression, maintain quality of life, and prevent disability. However, an estimated 43% of patients are not receiving DMT. Current guidelines provide direction for making the diagnosis, identifying MS subtypes and choosing initial therapy for the relapsing-remitting forms of the disease. This review presents a summary of available DMT agents indicated for the treatment of patients with relapsing-remitting MS (RRMS), briefly touches upon the management of acute attacks, and highlights new therapies being investigated for RRMS, which show promise as adjuncts to or alternatives to currently accepted strategies. (Formulary. 2010;45:252-262.) C1 [Rosenzweig, Tamara M.; Hartman, Sarah] Univ Massachusetts, Sch Med, Clin Pharm Serv, Amherst, MA 01003 USA. [MacKenzie, Elizabeth] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Rosenzweig, TM (reprint author), Univ Massachusetts, Sch Med, Clin Pharm Serv, Amherst, MA 01003 USA. NR 60 TC 0 Z9 0 U1 0 U2 7 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 1082-801X J9 FORMULARY JI Formulary PD AUG PY 2010 VL 45 IS 8 BP 252 EP 262 PG 11 GA 645TN UT WOS:000281489200002 ER PT J AU Tracy, EE Wiler, JL Holschen, JC Patel, SS Ligda, KO AF Tracy, Erin E. Wiler, Jennifer L. Holschen, Jolie C. Patel, Soha Sumanchandra Ligda, Kristin Ondecko TI Topics to Ponder: Part-Time Practice and Pay Parity SO GENDER MEDICINE LA English DT Article DE women physicians; part-time practice; pay disparity ID WORK-LIFE BALANCE; UNITED-STATES; PHYSICIANS; MEDICINE; WOMEN; RADIOLOGISTS; GENERATION; FACULTY AB Background: The medical profession has undergone a significant demographic change, with a dramatic increase in the number of women applying to medical school and practicing medicine. Objectives: In recognition of the changing demographics in the medical profession, the American Medical Association's Women Physicians Congress (AMA-WPC) conducted a members' survey to identify the issues affecting women physicians and to ascertain certain practice characteristics. Methods: In 2008, an e-mail survey link was sent to a randomly selected nationwide sample of 4992 WPC members, and a second, identical survey was sent to 596 female AMA members, utilizing the Epocrates database (Epocrates, Inc., San Mateo, California). Two e-mail reminders were sent for the first survey, which had a 15% response rate. A quota of 148 physicians was received within 4 days and was utilized to interpret results from the second survey. Results: Achieving work life balance was a significant concern for 91% of the respondents (n = 884). Half of the respondents believed that pay is gender neutral, and 28% indicated that they were "somewhat or very concerned about sexual harassment." When queried regarding practice patterns, 29% of respondents indicated that they had worked part-time at some point during their careers. Conclusions: In this survey, women physicians indicated that gender pay disparity and sexual harassment remain important issues in the medical profession. Less than a third of respondents had ever worked part-time, which should be a consideration for physician workforce studies. Barriers to part-time practice may exist. (Gend Med. 2010;7:350-356) (C) 2010 Excerpta Medica Inc. C1 [Tracy, Erin E.] Massachusetts Gen Hosp, Boston, MA 02180 USA. [Wiler, Jennifer L.] Washington Univ, St Louis, MO USA. [Wiler, Jennifer L.] Univ Colorado, Denver, CO 80202 USA. [Holschen, Jolie C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Patel, Soha Sumanchandra] Univ S Florida, Coll Med, Tampa, FL USA. [Ligda, Kristin Ondecko] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. RP Tracy, EE (reprint author), Massachusetts Gen Hosp, Founders 406,55 Fruit St, Boston, MA 02180 USA. EM EETracy@partners.org RI Wiler, Jennifer/G-7676-2016 NR 26 TC 5 Z9 5 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1550-8579 J9 GENDER MED JI Gend. Med. PD AUG PY 2010 VL 7 IS 4 BP 350 EP 356 DI 10.1016/j.genm.2010.07.003 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 648VP UT WOS:000281722800008 PM 20869635 ER PT J AU Bogdan, R Perlis, RH Fagerness, J Pizzagalli, DA AF Bogdan, R. Perlis, R. H. Fagerness, J. Pizzagalli, D. A. TI The impact of mineralocorticoid receptor ISO/VAL genotype (rs5522) and stress on reward learning SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Anhedonia; cortisol; depression; endophenotype; gene; glucocorticoid; HPA; mineralocorticoid; reward; stress ID PERCEIVED STRESS; MAJOR DEPRESSION; HEDONIC CAPACITY; HUMANS; INCREASES; CORTISOL; RESPONSIVENESS; NEUROENDOCRINE; CANRENOATE; DISORDERS AB Research suggests that stress disrupts reinforcement learning and induces anhedonia. The mineralocorticoid receptor (MR) determines the sensitivity of the stress response, and the missense iso/val polymorphism (IIe180Val, rs5522) of the MR gene (NR3C2) has been associated with enhanced physiological stress responses, elevated depressive symptoms and reduced cortisol-induced MR gene expression. The goal of these studies was to evaluate whether rs5522 genotype and stress independently and interactively influence reward learning. In study 1, participants (n = 174) completed a probabilistic reward task under baseline (i.e. no-stress) conditions. In study 2, participants (n = 53) completed the task during a stress (threat-of-shock) and no-stress condition. Reward learning, i.e. the ability to modulate behavior as a function of reinforcement history, was the main variable of interest. In study 1, in which participants were evaluated under no-stress conditions, reward learning was enhanced in val carriers. In study 2, participants developed a weaker response bias toward a more frequently rewarded stimulus under the stress relative to no-stress condition. Critically, stress-induced reward learning deficits were largest in val carriers. Although preliminary and in need of replication due to small sample size, findings indicate that psychiatrically healthy individuals carrying the MR val allele, gene, which has been recently linked to depression, showed a reduced ability to modulate behavior as a function of reward when facing an acute, uncontrollable stressor. Future studies are warranted to evaluate whether rs5522 genotype interacts with naturalistic stressors to increase the risk of depression and whether stress-induced anhedonia might moderate such risk. C1 [Bogdan, R.; Pizzagalli, D. A.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Perlis, R. H.; Fagerness, J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Perlis, R. H.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Perlis, R. H.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Pizzagalli, DA (reprint author), Harvard Univ, Dept Psychol, William James Hall 1220,33 Kirkland St, Cambridge, MA 02138 USA. EM dap@wjh.harvard.edu OI Bogdan, Ryan/0000-0002-1430-1045 FU NIH [R01 (MH68376), R21 (MH078979)]; Sackler Scholarship; NIMH NRSA [R90; DA023427-01] FX This work was supported by NIH R01 (MH68376) and R21 (MH078979) grants to D.A.P. and a Sackler Scholarship and NIMH NRSA predoctoral training grant (R90; DA023427-01) to R.B. The authors would like to thank Jeffrey Birk, Sara Dainese, Brian Galloway, Elena Goetz, Allison Jahn, Yuliya Nikolova, Miles Nugent, James O'Shea, Kyle Ratner, Sara Rubinstein, Ritchie Siburian, Sunny Dutra and Yan Emily Yuan for study assistance. Dr D.A.P. has received consulting fees from ANT North America Inc. (Advanced Neuro Technology) and AstraZeneca, and honoraria from AstraZeneca. Dr R.H.P. has received speakers or consulting fees/honoraria from AstraZeneca, BMS, Eli Lilly & Co., GSK, Pfizer, Concordant Rater Systems and Proteus Biomedical. Dr R.H.P. is a major stockholder in Concordant Rater Systems, LLC. R.B. and J.F. report no competing interests. NR 54 TC 26 Z9 27 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD AUG PY 2010 VL 9 IS 6 BP 658 EP 667 DI 10.1111/j.1601-183X.2010.00600.x PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 640FA UT WOS:000281032700012 PM 20528958 ER PT J AU Klusmann, JH Godinho, FJ Heitmann, K Maroz, A Koch, ML Reinhardt, D Orkin, SH Li, Z AF Klusmann, Jan-Henning Godinho, Frank J. Heitmann, Kirsten Maroz, Aliaksandra Koch, Mia Lee Reinhardt, Dirk Orkin, Stuart H. Li, Zhe TI Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis SO GENES & DEVELOPMENT LA English DT Article DE DS-AMKL; Down syndrome; GATA1; IGF signaling; IGF1R; megakaryoblastic leukemia ID HEMATOPOIETIC STEM-CELLS; FACTOR-II GENE; DOWN-SYNDROME; GROWTH-FACTOR; MEGAKARYOBLASTIC LEUKEMIA; CYCLE PROGRESSION; MEGAKARYOCYTIC LEUKEMIA; TARGET GENES; INSULIN; TRANSCRIPTION AB Oncogene-mediated transformation of hematopoietic cells has been studied extensively, but little is known about the molecular basis for restriction of oncogenes to certain target cells and differential cellular context-specific requirements for oncogenic transformation between infant and adult leukemias. Understanding cell type-specific interplay of signaling pathways and oncogenes is essential for developing targeted cancer therapies. Here, we address the vexing issue of how developmental restriction is achieved in Down syndrome acute megakaryoblastic leukemia (DS-AMKL), characterized by the triad of fetal origin, mutated GATA1 (GATA1s), and trisomy 21. We demonstrate overactivity of insulin-like growth factor (IGF) signaling in authentic human DS-AMKL and in a DS-AMKL mouse model generated through retroviral insertional mutagenesis. Fetal but not adult megakaryocytic progenitors are dependent on this pathway. GATA1 restricts IGF-mediated activation of the E2F transcription network to coordinate proliferation and differentiation. Failure of a direct GATA1-E2F interaction in mutated GATA1s converges with overactive IGF signaling to promote cellular transformation of DS fetal progenitors, revealing a complex, fetal stage-specific regulatory network. Our study underscores context-dependent requirements during oncogenesis, and explains resistance to transformation of ostensibly similar adult progenitors. C1 [Klusmann, Jan-Henning; Godinho, Frank J.; Orkin, Stuart H.; Li, Zhe] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Klusmann, Jan-Henning; Heitmann, Kirsten; Maroz, Aliaksandra; Koch, Mia Lee; Reinhardt, Dirk] Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. [Godinho, Frank J.; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Koch, Mia Lee; Li, Zhe] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Orkin, Stuart H.; Li, Zhe] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Orkin, Stuart H.; Li, Zhe] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM Stuart_Orkin@dfci.harvard.edu RI Reinhardt, Dirk/D-3939-2011; Klusmann, Jan-Henning/M-9655-2015 OI Reinhardt, Dirk/0000-0003-4313-9056; Klusmann, Jan-Henning/0000-0002-1070-0727 FU NCI; German National Academic Foundation [KL-2374/1-1]; NIH FX We thank Dr. H. Hock, J. Schindler, J. Schoning, T.V. Raghavan, K. Bohmer, M. Wackerhahn, T. Pushpanathan, Dr. J. Skokowa, K. Gupta, Dr. B. Thakur, and Dr. Y. Fujiwara for suggestions and/or technical assistance; M. Hamblen for general laboratory support; G. Losyev and Dr. M. Ballmaier for cell sorting; Dr. M. Zimmermann for statistical assistance; Drs. A. Schambach and C. Baum for providing plasmids and assistance with lentiviral transduction; Dr. N. von Neuhoff for providing support and assistance with protein analyses; Drs. K. Bernt and S. Armstrong for Mll-Af9 leukemic cells; and Dr. A. Cantor for the BioGata1/BioGata1s constructs and for sharing unpublished data. Z.L. was a Fellow of the Leukemia and Lymphoma Society, and was supported by a K99 Pathway-to-Independence award from NCI. This work was supported by a grant to J.H.K. and D.R. from the German National Academic Foundation (KL-2374/1-1), and a grant to S.H.O. from the NIH. S.H.O. is an Investigator of the Howard Hughes Medical Institute. NR 51 TC 57 Z9 58 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 1 PY 2010 VL 24 IS 15 BP 1659 EP 1672 DI 10.1101/gad.1903410 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 634QE UT WOS:000280597200012 PM 20679399 ER PT J AU Apger, J Reubens, M Henderson, L Gouge, CA Ilic, N Zhou, HH Christensen, TW AF Apger, Jennifer Reubens, Michael Henderson, Laura Gouge, Catherine A. Ilic, Nina Zhou, Helen H. Christensen, Tim W. TI Multiple Functions for Drosophila Mcm10 Suggested Through Analysis of Two Mcm10 Mutant Alleles SO GENETICS LA English DT Article ID DNA POLYMERASE-ALPHA; ORIGIN RECOGNITION COMPLEX; SACCHAROMYCES-CEREVISIAE; HETEROCHROMATIN PROTEIN-1; REPLICATION FACTORS; CHROMOSOME STRUCTURE; CATALYTIC SUBUNIT; BUDDING YEAST; CHROMATIN; INITIATION AB DNA replication and the correct packaging of DNA into different states of chromatin are both essential processes in all eukaryotic cells. High-fidelity replication of DNA is essential for the transmission of genetic material to cells. Likewise the maintenance of the epigenetic chromatin states is essential to the faithful reproduction of the transcriptional state of the cell. It is becoming more apparent that these two processes are linked through interactions between DNA replication proteins and chromatin-associated proteins. In addition, more proteins are being discovered that have dual roles in both DNA replication and the maintenance of epigenetic states. We present an analysis of two Drosophila mutants in the conserved DNA replication protein Mcm10. A hypomorphic mutant demonstrates that Mcm10 has a role in heterochromatic silencing and chromosome condensation, while the analysis of a novel C-terminal truncation allele of Mcm10 suggests that an interaction with Mcm2 is not required for chromosome condensation and heterochromatic silencing but is important for DNA replication. C1 [Apger, Jennifer; Reubens, Michael; Henderson, Laura; Gouge, Catherine A.; Christensen, Tim W.] E Carolina Univ, Dept Biol, Greenville, NC 27858 USA. [Ilic, Nina] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhou, Helen H.] ZS Associates, Boston, MA 02108 USA. RP Christensen, TW (reprint author), E Carolina Univ, Dept Biol, Howell Sci Complex,S309, Greenville, NC 27858 USA. EM christensent@ecu.edu FU Hughes Undergraduate Research and Cornell Presidential Research Scholars programs; National Science Foundation [NSF 0453773]; East Carolina University; National Institutes of Health [1R15GM093328-01] FX We thank and are grateful to Bik Tye for providing support for the initial work and Ross MacIntyre for advice and reagents, especially his contribution of expertise and flies lines for the PEV analysis. We thank Patrick Ferree, Bonnie Bolkan, Daniel Barbash, Janice Werner, Michael Goldberg, Byron Wilson, and members of the Cornell Superfly group for input and advice. We also thank Alexey A. Soshnev from Carver College of Medicine for useful advice concerning ovary dissection and nurse cell visualization. In addition, at East Carolina University Tom Fink of the Imaging Core supported our imaging efforts. Support for undergraduate research on this project was provided by the Hughes Undergraduate Research and Cornell Presidential Research Scholars programs. Support for the initial work was provided by the National Science Foundation (NSF 0453773). Finally we thank East Carolina University for start-up funds and the National Institutes of Health (grant 1R15GM093328-01 awarded to T.W.C.). NR 49 TC 16 Z9 16 U1 0 U2 2 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 2010 VL 185 IS 4 BP 1151 EP U44 DI 10.1534/genetics.110.117234 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 651EM UT WOS:000281907700003 PM 20498296 ER PT J AU Tseveleki, V Rubio, R Vamvakas, SS White, J Taoufik, E Petit, E Quackenbush, J Probert, L AF Tseveleki, Vivian Rubio, Renee Vamvakas, Sotiris-Spyros White, Joseph Taoufik, Era Petit, Edwige Quackenbush, John Probert, Lesley TI Comparative gene expression analysis in mouse models for multiple sclerosis, Alzheimer's disease and stroke for identifying commonly regulated and disease-specific gene changes SO GENOMICS LA English DT Article DE cDNA microarrays; Brain inflammation; Cerebral stroke; Alzheimer's disease; Systems biology; Gene expression profiling ID AUTOIMMUNE ENCEPHALOMYELITIS; MICROARRAY ANALYSIS; NEURITE OUTGROWTH; ISCHEMIC-STROKE; NEURONAL DEATH; ANIMAL-MODEL; BRAIN; CELLS; BETA; DEMYELINATION AB The brain responds to injury and infection by activating innate defense and tissue repair mechanisms. Working upon the hypothesis that the brain defense response involves common genes and pathways across diverse pathologies, we analysed global gene expression in brain from mouse models representing three major central nervous system disorders, cerebral stroke, multiple sclerosis and Alzheimer's disease compared to normal brain using DNA microarray expression profiling. A comparison of dysregulated genes across disease models revealed common genes and pathways including key components of estrogen and TGF-beta signaling pathways that have been associated with neuroprotection as well as a neurodegeneration mediator, TRPM7. Further, for each disease model, we discovered collections of differentially expressed genes that provide novel insight into the individual pathology and its associated mechanisms. Our data provide a resource for exploring the complex molecular mechanisms that underlie brain neurodegeneration and a new approach for identifying generic and disease-specific targets for therapy. (C) 2010 Elsevier Inc. All rights reserved. C1 [Tseveleki, Vivian; Vamvakas, Sotiris-Spyros; Taoufik, Era; Probert, Lesley] Hellenic Pasteur Inst, Mol Genet Lab, Athens 11521, Greece. [Rubio, Renee; White, Joseph; Quackenbush, John] Dana Farber Canc Inst, Lab Computat Biol & Funct Genom, Boston, MA 02115 USA. [Rubio, Renee; White, Joseph; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Petit, Edwige] Univ Caen, Ctr Cyceron, CNRS, UMR 6185, F-14032 Caen, France. RP Probert, L (reprint author), Hellenic Pasteur Inst, Mol Genet Lab, Athens 11521, Greece. EM vtseveleki@pasteur.gr; rrubio@jimmy.harvard.edu; vamvakas@bio.demokritos.gr; jwhite@jimmy.harvard.edu; etaoufik@pasteur.gr; epetit@cyceron.fr; johnq@jimmy.harvard.edu; lesley@pasteur.gr RI PETIT, Edwige/C-1896-2008 FU Greek Secretariat of Research and Technology, EPAN Greece-USA; European Union; NeuroproMiSe [LSHM-CT-2005-018637] FX This work was supported by a bidirectional collaboration research program from the Greek Secretariat of Research and Technology, EPAN Greece-USA and by the 6th Framework Program of the European Union, NeuroproMiSe, LSHM-CT-2005-018637. We wish to thank Matthias Staufenbiel (Novartis Pharma Ltd., Basel, Switzerland) for providing the APP23 mice. We wish to extend our special thanks to Adriana Ahumada, Razvan Sultana, Tove Anderson, Brian Frank and other members of the Quackenbush laboratory and Nikos Simos, Anda Voulgari-Kokota and Christos Georgiadis from the Probert laboratory for help and discussions. NR 50 TC 30 Z9 31 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG PY 2010 VL 96 IS 2 BP 82 EP 91 DI 10.1016/j.ygeno.2010.04.004 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 632RA UT WOS:000280443800003 PM 20435134 ER PT J AU Chapman, E Venkat, P Ko, E Orezzoli, JP Del Carmen, M Garner, EIO AF Chapman, Eloise Venkat, Pavithra Ko, Emily Orezzoli, Jorge P. Del Carmen, Marcela Garner, Elizabeth I. O. TI Use of multimedia as an educational tool to improve human papillomavirus vaccine acceptability-A pilot study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Human papillomavirus (HPV); Vaccine; Education; Acceptability; Survey; Disparity ID HPV VACCINATION; PUBLIC-HEALTH; UNITED-STATES; ADOLESCENTS; PARENTS; ACCEPTANCE; INFECTION; ATTITUDES; POLITICS; CANCER AB Objective. To determine, through a pilot study, whether use of a video-based educational tool can influence overall human papillomavirus (HPV) vaccine acceptability, views on vaccine mandates, school vaccination, and acceptable age for vaccination. Methods. Written surveys addressing HPV knowledge and vaccine acceptability were administered to study participants from January to March 2007. An initial 32-question survey was completed, followed by an 8-minute educational video, and a post-video assessment. Results. Out of 256 subjects, 73.0% watched the video and completed all surveys. Eighty percent of the subjects had heard of HPV, while 65.0% knew, prior to viewing the video, that the vaccine was available. Individual vaccine acceptability increased from 66.7% to 78.0% after the video (p = .0014). Prior to the video, 54.8% of subjects supported mandatory HPV vaccination, with 51.1% supporting school vaccination, and 66.7% accepting vaccination if it were free. After the video, these percentages increased to 72.6% (p<.0001), 65.1% (p<.0001) and 86.6% (p<.0001) respectively. Initially, 56.5% of subjects would vaccinate their child at 15 years of age or younger. After the video, 94.1% approved of vaccination from age 9 (p<.0001). Secondary analysis revealed Hispanics, African Americans, and lower income families were more likely to accept HPV vaccination after the video. A perception that vaccination promotes sex, and whether or not participants talk to their children about sex, did not affect acceptability. Conclusion. Using an educational video significantly increased overall HPV vaccine acceptability and acceptance in younger age groups. This may be an effective means of increasing awareness and acceptability of HPV vaccination. (C) 2010 Elsevier Inc. All rights reserved. C1 [Chapman, Eloise; Venkat, Pavithra; Ko, Emily; Garner, Elizabeth I. O.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Orezzoli, Jorge P.; Del Carmen, Marcela] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Chapman, Eloise; Ko, Emily; Orezzoli, Jorge P.; Del Carmen, Marcela; Garner, Elizabeth I. O.] Harvard Univ, Sch Med, Boston, MA USA. RP Chapman, E (reprint author), Northwestern Univ, Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, 250 E Super St,5-2168, Chicago, IL 60611 USA. EM eloise.chapman@gmail.com FU Harvard Medical School Center for Excellence in Minority Health and Health Disparities; Yale School of Medicine FX This study was supported by a fellowship from the Harvard Medical School Center for Excellence in Minority Health and Health Disparities and the Yale School of Medicine Student Research Program. NR 24 TC 8 Z9 9 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD AUG 1 PY 2010 VL 118 IS 2 BP 103 EP 107 DI 10.1016/j.ygyno.2010.04.010 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 627LB UT WOS:000280039900002 PM 20457469 ER PT J AU Ruchelsman, DE Mudgal, CS Jupiter, JB AF Ruchelsman, David E. Mudgal, Chaitanya S. Jupiter, Jesse B. TI The Role of Locking Technology in the Hand SO HAND CLINICS LA English DT Article DE Locking plates; Metacarpal and phalanx fractures; Hand trauma ID PROXIMAL HUMERUS FRACTURES; DISTAL RADIAL FRACTURES; INVASIVE STABILIZATION SYSTEM; PLATE FIXATION; PHALANGEAL FRACTURES; METACARPAL FRACTURES; MINICONDYLAR PLATE; INTERNAL-FIXATION; FEMORAL FRACTURES; FEMUR FRACTURES AB Locked fixed-angle plating in the hand and wrist helps to optimize outcomes following surgical fixation of select acute fractures and complex reconstructions. Select indications include unstable distal ulna head/neck fractures, periarticular metacarpal and phalangeal fractures, comminuted/multifragmentary diaphyseal fractures with bone loss (ie, combined injuries of the hand), osteopenic/pathologic fractures, non-unions and corrective osteotomy fixation, and small joint arthrodesis. Locked plating techniques in the hand should not be seen as a panacea for wrist and digital acute trauma and delayed reconstructions. An understanding of the biomechanics of fixed-angle plating and proper technical application of locking constructs will optimize outcomes and minimize complications. As clinical experience with locking technology in hand trauma broadens, new indications and applications will emerge. Currently, several systems are available. The specific implants share common features in their protocols for insertion, but unique differences in their design (ie, individual locking mechanisms, uniaxial vs polyaxial locking capability, metallurgy, and plate profiles) must be appreciated and considered preoperatively. C1 [Ruchelsman, David E.; Mudgal, Chaitanya S.; Jupiter, Jesse B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. [Ruchelsman, David E.; Mudgal, Chaitanya S.; Jupiter, Jesse B.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand & Upper Extrem Serv,Yawkey Ctr, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 63 TC 10 Z9 11 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD AUG PY 2010 VL 26 IS 3 BP 307 EP + DI 10.1016/j.hcl.2010.04.001 PG 14 WC Orthopedics SC Orthopedics GA 644CX UT WOS:000281349800002 PM 20670796 ER PT J AU Monica, JT Mudgal, CS AF Monica, James T. Mudgal, Chaitanya S. TI Radial Head Arthroplasty SO HAND CLINICS LA English DT Article DE Radial head; Fracture; Arthroplasty ID VALGUS STABILITY; FRACTURES; ELBOW; REPLACEMENT; PROSTHESIS; EXCISION AB Radial head arthroplasty remains an encouraging treatment option for comminuted radial head fractures in an unstable elbow or forearm. This article discusses the surgical considerations related to radial head arthroplasty, including anatomy, indications, and surgical technique. Radial head arthroplasty outcomes literature and a review of current implant options are also discussed. C1 [Monica, James T.; Mudgal, Chaitanya S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Yawkey Ctr, Hand & Upper Extrem Surg Serv,Dept Orthopaed Surg, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Yawkey Ctr, Hand & Upper Extrem Surg Serv,Dept Orthopaed Surg, 55 Fruit St,Suite 2100, Boston, MA 02114 USA. EM cmudgal@partners.org NR 31 TC 2 Z9 2 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 0749-0712 J9 HAND CLIN JI Hand Clin. PD AUG PY 2010 VL 26 IS 3 BP 403 EP + DI 10.1016/j.hcl.2010.04.008 PG 9 WC Orthopedics SC Orthopedics GA 644CX UT WOS:000281349800011 PM 20670805 ER PT J AU Guitton, TG Ring, D AF Guitton, Thierry G. Ring, David TI Three-Dimensional Computed Tomographic Imaging and Modeling in the Upper Extremity SO HAND CLINICS LA English DT Article DE Computed tomography; Imaging; Modeling; Upper extremity ID CORRECTIVE OSTEOTOMY; FRACTURES; RADIUS; RELIABILITY AB Technologic advances in imaging of the upper extremity have taken an immense leap in the last decade. So has the amount of research that has been published on this subject. Three-dimensional (3D) reconstructions, in particular, have improved identification of fracture characteristics, such as fragments, fracture edges, and articular surfaces. Three-dimensional physical models can even increase the advantages of the 3D reconstructions. Together, 3D reconstructions and physical modeling may outweigh the disadvantages of increased cost, resource usage, and additional time, as research has shown that it can benefit both the surgeon and the patient significantly. C1 [Guitton, Thierry G.; Ring, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Guitton, Thierry/0000-0002-2599-1985 NR 12 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD AUG PY 2010 VL 26 IS 3 BP 447 EP + DI 10.1016/j.hcl.2010.04.007 PG 8 WC Orthopedics SC Orthopedics GA 644CX UT WOS:000281349800015 PM 20670809 ER PT J AU Francis, NA Guinan, JJ AF Francis, Nikolas A. Guinan, John J., Jr. TI Acoustic stimulation of human medial olivocochlear efferents reduces stimulus-frequency and click-evoked otoacoustic emission delays: Implications for cochlear filter bandwidths SO HEARING RESEARCH LA English DT Article ID SUPERIOR OLIVARY COMPLEX; AUDITORY-NERVE RESPONSES; TUNING CURVES; CONTRALATERAL SUPPRESSION; WAVELET ANALYSIS; REFLEX; DEPENDENCE; PHASE; MODEL; SOUND AB Filter theory indicates that changes in cochlear filter bandwidths are accompanied by changes in cochlear response latencies. Previous reports indicate that otoacoustic emission (OAE) delays are reduced by exciting medial olivocochlear (MOC) efferents with contralateral broad-band noise (CBBN). These delay reductions are consistent with MOC-induced widening of cochlear filters. We quantified the MOC-induced changes in human cochlear filter-related delays using stimulus-frequency and click-evoked OAEs (SFOAE and CEOAEs), recorded with and without MOC activity elicited by 60 dB SPL CBBN. MOC-induced delay changes were measured from the slopes of SFOAE phase functions and from cross-correlation of 500 Hz-wide CEOAE frequency-band waveform magnitudes. The delay changes measured from CEOAEs and SFOAEs were statistically indistinguishable. Both showed greater delay reductions at lower frequencies (a 5% decrease in the 0.5-2 kHz frequency region). These data indicate that cochlear filters are widened 5% by the MOC activity from moderate-level CBBN. Psychophysically, the large changes in cochlear response latencies, implied by the 0.5 ms change in OAE delay at low frequencies, would have a profound effect on binaural localization if they were not balanced in the central nervous system, or by the MOC system producing similar changes in both ears. (C) 2010 Elsevier B.V. All rights reserved. C1 [Francis, Nikolas A.; Guinan, John J., Jr.] Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. [Francis, Nikolas A.; Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs Auditory Physiol, Dept Otolaryngol, Boston, MA 02114 USA. [Guinan, John J., Jr.] Harvard Univ, Dept Otol & Laryngol, Sch Med, Boston, MA 02115 USA. RP Francis, NA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM nfu@mit.edu FU NIH NIDCD [RO1 DC005977, P30 DC005209, T32 DC00038] FX We thank Radha Kalluri, Jeffery Lichtenhan and Christopher Shera for comments on the manuscript. Supported by NIH NIDCD RO1 DC005977, P30 DC005209 and T32 DC00038. NR 62 TC 31 Z9 31 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD AUG 1 PY 2010 VL 267 IS 1-2 BP 36 EP 45 DI 10.1016/j.heares.2010.04.009 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 631MO UT WOS:000280351700005 PM 20430088 ER PT J AU Hou, JB Qi, H Zhang, MM Ma, LJ Liu, HM Han, ZG Meng, LB Yang, SA Zhang, SS Yu, B Jang, IK AF Hou, Jingbo Qi, Hai Zhang, Maomao Ma, Lijia Liu, Huimin Han, Zhigang Meng, Lingbo Yang, Shuang Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI Development of lipid-rich plaque inside bare metal stent: possible mechanism of late stent thrombosis? An optical coherence tomography study SO HEART LA English DT Article ID CORONARY-ARTERY-DISEASE; SIROLIMUS-ELUTING STENT; FOLLOW-UP; BALLOON ANGIOPLASTY; IMPLANTATION; PLACEMENT AB Aims To study in-stent tissue characteristics by optical coherence tomography (OCT) at long-term follow-up in patients with previous bare metal stent implantation. Methods and results Among 1636 patients who underwent bare metal stent (BMS) implantation between 1999 and 2006, 39 patients with 60 BMS who developed recurrent ischaemia underwent repeat catheterisation and OCT imaging between June 2008 and August 2009. The average time interval between initial BMS implantation and OCT imaging was 6.5 +/- 1.3 years. A lesion that had features of lipid-rich plaque was found in 20 stents (33.3%) in 16 patients (41%). Fibrous intima was observed in the remaining 40 stents. In the group with lipid-rich plaque, average fibrous cap thickness was 56.7 +/- 5.8 mu m and lipid arc was 173 +/- 58. Six patients had evidence of recent plaque disruption and another six patients had mural thrombus. Hypertension and smoking were more common in these patients than in those with fibrous intima. Conclusions Lipid-rich plaque with a thin fibrous cap was seen in patients with previous BMS implantation and recurrent ischaemia at late follow-up. This may be one possible mechanism for late stent thrombosis. C1 [Hou, Jingbo; Qi, Hai; Zhang, Maomao; Ma, Lijia; Liu, Huimin; Han, Zhigang; Meng, Lingbo; Yang, Shuang; Yu, Bo] Harbin Med Coll, Affiliated Hosp 2, Dept Cardiol, Key Labs Educ,Minist Myocardial Ischaemia Mech &, Harbin, Heilongjiang, Peoples R China. [Zhang, Shaosong] LightLab Imaging Inc, Westford, MA USA. [Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CLIPI,Cardiol Div, Boston, MA USA. RP Yu, B (reprint author), Harbin Med Coll, Affiliated Hosp 2, Dept Cardiol, Key Labs Educ,Minist Myocardial Ischaemia Mech &, Harbin, Heilongjiang, Peoples R China. EM yubodr@163.com FU LightLab Imaging FX SZ is an employee of LightLab Imaging; IKJ received research grant from LightLab Imaging. NR 20 TC 34 Z9 35 U1 1 U2 3 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 AUG PY 2010 VL 96 IS 15 BP 1187 EP 1190 DI 10.1136/hrt.2010.194381 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 626HJ UT WOS:000279956700005 PM 20639235 ER PT J AU Milan, DJ Lubitz, SA Kaab, S Ellinor, PT AF Milan, David J. Lubitz, Steven A. Kaeaeb, Stefan Ellinor, Patrick T. TI Genome-wide association studies in cardiac electrophysiology: Recent discoveries and implications for clinical practice SO HEART RHYTHM LA English DT Article DE Genome wide association study; atrial fibrillation; gene; mutation ID QT INTERVAL DURATION; ATRIAL-FIBRILLATION; COMMON VARIANTS; PR INTERVAL; POTASSIUM CHANNEL; GENETIC-VARIATION; CHROMOSOME 4Q25; RISK; POPULATIONS; MUTATIONS AB Genome-wide association studies have been increasingly used to study the genetics of complex human diseases. Within the field of cardiac electrophysiology, this technique has been applied to conditions such as atrial fibrillation, and several electrocardiographic parameters including the QT interval. While these studies have identified multiple genomic regions associated with each trait, questions remain, including the best way to explore the pathophysiology of each association and the potential for clinical utility. This review will summarize recent genome-wide association study results within cardiac electrophysiology and discuss their broader implications in basic science and clinical medicine. C1 [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Milan, David J.; Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Kaeaeb, Stefan] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM pellinor@partners.org RI Kaab, Stefan/H-3915-2012 FU National Institutes of Health [K08HL076361, R21DA026982, HL092577, DA027021, T32HL007575]; Fondation Leducq [07-CVD 03]; German National Genome Research Network (NGFN) [01GS0838]; German AF-Net [01 GI 0204/N]; Exzellenzinitiative at Ludwig-Maximilians University, Munich FX Supported by grants from the National Institutes of Health (K08HL076361, R21DA026982, HL092577, DA027021, T32HL007575), Fondation Leducq (07-CVD 03), German National Genome Research Network (NGFN, 01GS0838), German AF-Net (01 GI 0204/N), and Exzellenzinitiative at Ludwig-Maximilians University, Munich. Address reprint requests and correspondence: Patrick T. Ellinor, Cardiac Arrhythmia Service, Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail address: pellinor@partners.org. (Received March 17, 2010; accepted April 21, 2010.) NR 40 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 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD AUG PY 2010 VL 7 IS 8 BP 1141 EP 1148 DI 10.1016/j.hrthm.2010.04.021 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 629ZE UT WOS:000280239300022 PM 20423731 ER PT J AU Rimbara, E Shulman, RJ Abraham, BP Sabounchi, S Attumi, TA Opekun, AR Graham, DY AF Rimbara, E. Shulman, R. J. Abraham, B. P. Sabounchi, S. Attumi, T. A. Opekun, A. R. Graham, D. Y. CA Baylor IBD Study Grp TI Detection of non-pylori Helicobacter species from IBD, IBS and healthy subjects: preliminary results SO HELICOBACTER LA English DT Meeting Abstract CT 23rd International Workshop on Helicobacter and Related Bacteria in Chronic Digestive Inflammation and Gastric Cancer CY SEP 16-18, 2010 CL Rotterdam, NETHERLANDS C1 [Rimbara, E.; Sabounchi, S.; Attumi, T. A.; Graham, D. Y.] VA Med Ctr, Houston, TX USA. [Shulman, R. J.; Abraham, B. P.; Opekun, A. R.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD AUG PY 2010 VL 15 IS 4 BP 325 EP 325 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 626SC UT WOS:000279986200042 ER PT J AU El-Serag, HB Talwalkar, J Kim, WR AF El-Serag, Hashem B. Talwalkar, Jayant Kim, W. Ray TI Efficacy, Effectiveness, and Comparative Effectiveness in Liver Disease SO HEPATOLOGY LA English DT Editorial Material ID HEPATITIS-C; UNITED-STATES; HEALTH-CARE; PREDICTORS; DISPARITIES; POPULATION; VETERANS; MEDICINE C1 [Talwalkar, Jayant; Kim, W. Ray] Mayo Clin, Div Gastroenterol & Hepatol, Coll Med, Rochester, MN 55906 USA. [Talwalkar, Jayant; Kim, W. Ray] Mayo Clin, Div Healthcare Policy & Res, Coll Med, Rochester, MN 55906 USA. [El-Serag, Hashem B.] Michael E DeBakey Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. [El-Serag, Hashem B.] Michael E DeBakey Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. [El-Serag, Hashem B.] Baylor Coll Med, Houston, TX 77030 USA. RP Kim, WR (reprint author), Mayo Clin, Div Gastroenterol & Hepatol, Coll Med, PL 6,200 1st St SW, Rochester, MN 55906 USA. EM kim.ray@mayo.edu NR 16 TC 24 Z9 25 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2010 VL 52 IS 2 BP 403 EP 407 DI 10.1002/hep.23819 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 633OZ UT WOS:000280513900001 PM 20683939 ER PT J AU Afzali, A Weiss, NS Boyko, EJ Ioannou, GN AF Afzali, Anita Weiss, Noel S. Boyko, Edward J. Ioannou, George N. TI Association Between Serum Uric Acid Level and Chronic Liver Disease in the United States SO HEPATOLOGY LA English DT Article ID ALANINE AMINOTRANSFERASE ACTIVITY; CIRRHOSIS-RELATED DEATH; CARDIOVASCULAR RISK; HYPERURICEMIA; POPULATION; PREVALENCE; HOSPITALIZATION; CONSUMPTION; PREDICTORS; OBESITY AB Elevated serum uric acid (UA) levels strongly reflect and may even cause oxidative stress, insulin resistance, and metabolic syndrome, which are risk factors for the progression of liver disease. We sought to determine whether serum UA levels are associated with the development of cirrhosis or the presence of elevated serum liver enzymes. We used cohort data from the first National Health and Nutrition Examination Survey (NHANES I) to determine whether the baseline serum UA level was associated with the incidence of hospitalization or death due to cirrhosis among 5518 participants during a mean follow-up of 12.9 years (range = 4-21 years) after the exclusion of the first 4 years of follow-up. We also used cross-sectional data from NHANES 1988-1994 (n = 10,993) and NHANES 19992006 (n = 6186) to determine whether the serum UA level was associated with elevated serum alanine aminotransferase (ALT) or gamma-glutamyl transferase (GGT), two markers of hepatic necroinflammation. Compared to persons in the lower third of the distribution of serum UA (<4.8 mg/dL), those in the top third (>6 mg/dL) had a higher risk of cirrhosis-related hospitalization or death [adjusted hazard ratio (AHR) = 2.8, 95% confidence interval (CI) =1.3-5.7], whereas the risk was not substantially increased in persons within the middle third (serum UA level = 2.6-4.8 mg/dL, AHR = 1.3, 95% CI = 0.6-2.7). A higher serum UA level was associated with greater mean serum ALT and GGT levels and a greater probability of elevated serum ALT and GGT. Conclusion: The serum UA level is associated with the development of cirrhosis and the presence of elevated serum liver enzymes after adjustments for important causes and risk factors of chronic liver disease. (HEPATOLOGY 2010;52:578-589) C1 [Afzali, Anita; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. [Afzali, Anita; Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA 98108 USA. [Boyko, Edward J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. [Weiss, Noel S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Afzali, Anita; Ioannou, George N.] Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA USA. [Boyko, Edward J.] Univ Washington, Dept Med, Div Internal Med, Seattle, WA USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, S-111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu FU NIDDK NIH HHS [P30 DK-17047] NR 27 TC 35 Z9 38 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2010 VL 52 IS 2 BP 578 EP 589 DI 10.1002/hep.23717 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 633OZ UT WOS:000280513900020 PM 20683957 ER PT J AU Mader, C Stolzmann, P Leschka, S Alkadhi, H Scheffel, H AF Mader, C. Stolzmann, P. Leschka, S. Alkadhi, H. Scheffel, Hans TI Hemoptysis - a sign of primary cardiac malignancy SO HERZ LA English DT Editorial Material C1 [Stolzmann, P.; Alkadhi, H.; Scheffel, Hans] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Stolzmann, P.; Alkadhi, H.; Scheffel, Hans] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mader, C.; Stolzmann, P.; Alkadhi, H.; Scheffel, Hans] Univ Zurich Hosp, Inst Diagnost & Intervent Radiol, Zurich, Switzerland. [Leschka, S.] Canton Hosp St Gallen, Inst Radiol, St Gallen, Switzerland. RP Scheffel, H (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 100 Charles River Plaza, Boston, MA 02114 USA. EM hscheffel@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0340-9937 J9 HERZ JI Herz PD AUG PY 2010 VL 35 IS 5 BP 355 EP 356 DI 10.1007/s00059-010-3357-8 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 641GL UT WOS:000281112700007 PM 20607199 ER PT J AU Tomas, E Stanojevic, V Habener, JF AF Tomas, E. Stanojevic, V. Habener, J. F. TI GLP-1 (9-36) Amide Metabolite Suppression of Glucose Production in Isolated Mouse Hepatocytes SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE hepatic insulin resistance; hyperglycemia; diabetes ID GLUCAGON-LIKE PEPTIDE-1; INSULIN-RESISTANCE; TISSUE DISTRIBUTION; RECEPTOR; EXPRESSION; EXENDIN-4; MICE; SENSITIVITY; SECRETION; HUMANS AB The glucoincretin hormone glucagon-like peptide-1 (GLP-1) augments glucose-stimulated insulin secretion and is in use as an effective treatment for diabetes. However, after its secretion from the intestine, the insulinotropic GLP-1 (7-36) amide hormone is rapidly inactivated by enzymatic cleavage by the diaminopeptidyl peptidase-4 giving rise to GLP-1 (9-36) amide. Inasmuch as most of the circulating GLP-1 is in the form of the metabolite GLP-1 (9-36) amide it has been suggested that it has insulin-like actions on peripheral insulin-sensitive tissues. In earlier studies, infusions of GLP-1 (9-36) amide in obese insulin-resistant subjects showed a marked suppression of hepatic glucose production. However, it remained uncertain whether the effects on glucose production were due to direct effects on hepatocytes, involved central or portal vein-mediated actions, or were mediated by insulin secretion. Here we show that GLP-1 (9-36) amide directly suppresses glucose production in isolated mouse hepatocytes ex vivo independent of the GLP-1 receptor. These findings support direct insulinomimetic actions of the GLP-1 metabolite on gluconeogenesis in hepatocytes that are independent of insulin action and the GLP-1 receptor, and suggest that GLP-1 (9-36) amide-based peptides might present a novel therapy for the treatment of excessive hepatic glucose production in individuals with insulin-resistant diabetes. C1 [Tomas, E.; Stanojevic, V.; Habener, J. F.] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Thier 306,55 Fruit St, Boston, MA 02114 USA. EM jhabener@partners.org FU Merck Company FX We thank Karen McManus for important help with the studies. This work was supported in part by an Investigator-initiated Studies Program Pilot Grant from Merck & Company. NR 30 TC 25 Z9 30 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD AUG PY 2010 VL 42 IS 9 BP 657 EP 662 DI 10.1055/s-0030-1253421 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 631TG UT WOS:000280370400007 PM 20645222 ER PT J AU Pawlyk, BS Bulgakov, OV Liu, XQ Xu, XY Adamian, M Sun, X Khani, SC Berson, EL Sandberg, MA Li, TS AF Pawlyk, Basil S. Bulgakov, Oleg V. Liu, Xiaoqing Xu, Xiaoyun Adamian, Michael Sun, Xun Khani, Shahrokh C. Berson, Eliot L. Sandberg, Michael A. Li, Tiansen TI Replacement Gene Therapy with a Human RPGRIP1 Sequence Slows Photoreceptor Degeneration in a Murine Model of Leber Congenital Amaurosis SO HUMAN GENE THERAPY LA English DT Article ID RECOMBINANT ADENOASSOCIATED VIRUS; REGULATOR (RPGR)-INTERACTING PROTEIN; RETINITIS-PIGMENTOSA; ROD PHOTORECEPTOR; RESTORES VISION; MUTATIONS; IDENTIFICATION; MORPHOGENESIS; LOCALIZATION; TRANSDUCTION AB RPGR-interacting protein-1 (RPGRIP1) is localized in the photoreceptor-connecting cilium, where it anchors the RPGR (retinitis pigmentosa GTPase regulator) protein, and its function is essential for photoreceptor maintenance. Genetic defect in RPGRIP1 is a known cause of Leber congenital amaurosis (LCA), a severe, early-onset form of retinal degeneration. We evaluated the efficacy of replacement gene therapy in a murine model of LCA carrying a targeted disruption of RPGRIP1. The replacement construct, packaged in an adeno-associated virus serotype 8 (AAV8) vector, used a rhodopsin kinase gene promoter to drive RPGRIP1 expression. Both promoter and transgene were of human origin. After subretinal delivery of the replacement gene in the mutant mice, human RPGRIP1 was expressed specifically in photoreceptors, localized correctly in the connecting cilia, and restored the normal localization of RPGR. Electroretinogram and histological examinations showed better preservation of rod and cone photoreceptor function and improved photoreceptor survival in the treated eyes. This study demonstrates the efficacy of human gene replacement therapy and validates a gene therapy design for future clinical trials in patients afflicted with this condition. Our results also have therapeutic implications for other forms of retinal degenerations attributable to a ciliary defect. C1 [Pawlyk, Basil S.; Bulgakov, Oleg V.; Liu, Xiaoqing; Xu, Xiaoyun; Adamian, Michael; Sun, Xun; Berson, Eliot L.; Sandberg, Michael A.; Li, Tiansen] Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. [Pawlyk, Basil S.; Bulgakov, Oleg V.; Liu, Xiaoqing; Xu, Xiaoyun; Adamian, Michael; Sun, Xun; Berson, Eliot L.; Sandberg, Michael A.; Li, Tiansen] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Khani, Shahrokh C.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Li, TS (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. EM Tiansen.Li@nih.gov FU National Eye Institute [EY10581]; NEI [P30EY14104]; Foundation Fighting Blindness; Foundation for Retina Research; Massachusetts Lions Eye Research Fund FX The authors thank Dr. Jeng-Shin Lee at the Research Vector Core of Harvard Medical School for AAV vector packaging, the National Disease Research Interchange for providing human retinal tissue, and Norman Michaud for select tissue processing for light microscopy. This work was supported by National Eye Institute grant EY10581, an NEI core grant for Vision Research (P30EY14104), the Foundation Fighting Blindness, the Foundation for Retina Research, and the Massachusetts Lions Eye Research Fund. NR 43 TC 41 Z9 42 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG PY 2010 VL 21 IS 8 BP 993 EP 1004 DI 10.1089/hum.2009.218 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 636RK UT WOS:000280757200009 PM 20384479 ER PT J AU Schumacher, FR Cheng, I Freedman, ML Mucci, L Allen, NE Pollak, MN Hayes, RB Stram, DO Canzian, F Henderson, BE Hunter, DJ Virtamo, J Manjer, J Gaziano, JM Kolonel, LN Tjonneland, A Albanes, D Calle, EE Giovannucci, E Crawford, ED Haiman, CA Kraft, P Willett, WC Thun, MJ Marchand, LL Kaaks, R Feigelson, HS Bueno-De-Mesquita, HB Palli, D Riboli, E Lund, E Amiano, P Andriole, G Dunning, AM Trichopoulos, D Stampfer, MJ Key, TJ Ma, J AF Schumacher, Fredrick R. Cheng, Iona Freedman, Matthew L. Mucci, Lorelei Allen, Naomi E. Pollak, Michael N. Hayes, Richard B. Stram, Daniel O. Canzian, Frederico Henderson, Brian E. Hunter, David J. Virtamo, Jarmo Manjer, Jonas Gaziano, J. Michael Kolonel, Laurence N. Tjonneland, Anne Albanes, Demetrius Calle, Eugenia E. Giovannucci, Edward Crawford, E. David Haiman, Christopher A. Kraft, Peter Willett, Walter C. Thun, Michael J. Marchand, Loic Le Kaaks, Rudolf Feigelson, Heather Spencer Bueno-de-Mesquita, H. Bas Palli, Domenico Riboli, Elio Lund, Eliv Amiano, Pilar Andriole, Gerald Dunning, Alison M. Trichopoulos, Dimitrios Stampfer, Meir J. Key, Timothy J. Ma, Jing TI A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among SO HUMAN MOLECULAR GENETICS LA English DT Article ID GROWTH-FACTOR-I; GENOME-WIDE ASSOCIATION; FACTOR-BINDING PROTEIN-3; BREAST-CANCER; MULTIETHNIC COHORT; CIRCULATING LEVELS; FACTOR (IGF)-I; SERUM-LEVELS; MENDELIAN RANDOMIZATION; MISSING HERITABILITY AB The insulin-like growth factor (IGF) pathway has been implicated in prostate development and carcinogenesis. We conducted a comprehensive analysis, utilizing a resequencing and tagging single-nucleotide polymorphism (SNP) approach, between common genetic variation in the IGF1, IGF binding protein (BP) 1, and IGFBP3 genes with IGF-I and IGFBP-3 blood levels, and prostate cancer (PCa) risk, among Caucasians in the NCI Breast and Prostate Cancer Cohort Consortium. We genotyped 14 IGF1 SNPs and 16 IGFBP1/IGFBP3 SNPs to capture common [minor allele frequency (MAF) >= 5%] variation among Caucasians. For each SNP, we assessed the geometric mean difference in IGF blood levels (N = 5684) across genotypes and the association with PCa risk (6012 PCa cases/6641 controls). We present two-sided statistical tests and correct for multiple comparisons. A non-synonymous IGFBP3 SNP in exon 1, rs2854746 (Gly32Ala), was associated with IGFBP-3 blood levels (P-adj = 8.8 x 10(-43)) after adjusting for the previously established IGFBP3 promoter polymorphism A-202C (rs2854744); IGFBP-3 blood levels were 6.3% higher for each minor allele. For IGF1 SNP rs4764695, the risk estimates among heterozygotes was 1.01 (99% CI: 0.90-1.14) and 1.20 (99% CI: 1.06-1.37) for variant homozygotes with overall PCa risk. The corrected allelic P-value was 8.7 x 10(-3). IGF-I levels were significantly associated with PCa risk (P-trend = 0.02) with a 21% increase of PCa risk when compared with the highest quartile to the lowest quartile. We have identified SNPs significantly associated with IGFBP-3 blood levels, but none of these alter PCa risk; however, a novel IGF1 SNP, not associated with IGF-I blood levels, shows preliminary evidence for association with PCa risk among Caucasians. C1 [Mucci, Lorelei; Hunter, David J.; Giovannucci, Edward; Stampfer, Meir J.; Ma, Jing] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. [Schumacher, Fredrick R.; Stram, Daniel O.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Cheng, Iona; Kolonel, Laurence N.; Marchand, Loic Le] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mucci, Lorelei; Giovannucci, Edward; Willett, Walter C.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Gaziano, J. Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, MAVERIC, Boston, MA 02115 USA. [Allen, Naomi E.; Key, Timothy J.] Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7BN, England. [Pollak, Michael N.] McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Dept Med & Oncol,Canc Prevent Res Unit, Montreal, PQ H3T 1E2, Canada. [Hayes, Richard B.] NYU, Sch Med, New York, NY 10016 USA. [Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, FIN-00300 Helsinki, Finland. [Manjer, Jonas] Malmo Univ Hosp, Dept Surg, S-20502 Malmo, Sweden. [Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. [Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Calle, Eugenia E.; Thun, Michael J.; Feigelson, Heather Spencer] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30303 USA. [Crawford, E. David] Univ Colorado, Denver Hlth Sci Ctr, Denver, CO 80045 USA. [Feigelson, Heather Spencer] Kaiser Permanente, Denver, CO 80237 USA. [Bueno-de-Mesquita, H. Bas; Amiano, Pilar] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. [Palli, Domenico] ISPO Canc Res & Prevent Inst, Mol & Nutrit Epidemiol Unit, I-50139 Florence, Italy. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London SW7 2AZ, England. [Lund, Eliv] Univ Tromso, Inst Community Med, N-9019 Tromso, Norway. [Andriole, Gerald] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England. [Trichopoulos, Dimitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens 11527, Greece. RP Ma, J (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM jing.ma@channing.harvard.edu RI Pollak, Michael/G-9094-2011; Albanes, Demetrius/B-9749-2015; OI Pollak, Michael/0000-0003-3047-0604; Dunning, Alison Margaret/0000-0001-6651-7166; PALLI, Domenico/0000-0002-5558-2437 FU National Cancer Institute (NCI) [U01 CA098216, U01 CA098233, U01 CA098758, U01 CA098710, CA-34944, CA-40360, CA-097193]; National Research Service Award Training Program in Cancer Epidemiology [T32 CA009001-32]; NHLBI [HL-26490, HL-34595]; Department of Health and Human Services, National Cancer Institute [N01-CN-45165, N01-RC-45035, N01-RC-37004]; [CA54281]; [CA63464] FX This work was funded by National Cancer Institute (NCI) grants U01 CA098216 (EPIC), U01 CA098233 (Harvard), U01 CA098758 (MEC) and U01 CA098710 (ACS). F. R. S. was supported by the National Research Service Award Training Program in Cancer Epidemiology (T32 CA009001-32). The Physicians' Health Study was supported by the NCI (CA-34944, CA-40360 and CA-097193) and the NHLBI (HL-26490 and HL-34595). The Multiethnic Cohort was supported by CA54281 and CA63464. The ATBC Study was supported by US Public Health Service contracts N01-CN-45165, N01-RC-45035 and N01-RC-37004 from the Department of Health and Human Services, National Cancer Institute. NR 97 TC 32 Z9 32 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 1 PY 2010 VL 19 IS 15 BP 3089 EP 3101 DI 10.1093/hmg/ddq210 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 633HA UT WOS:000280491200015 PM 20484221 ER PT J AU Boisvert, H Duncan, MJ AF Boisvert, Heike Duncan, Margaret J. TI Translocation of Porphyromonas gingivalis Gingipain Adhesin Peptide A44 to Host Mitochondria Prevents Apoptosis SO INFECTION AND IMMUNITY LA English DT Article ID STAUROSPORINE-INDUCED APOPTOSIS; TRACHOMATIS-INFECTED CELLS; HUMAN EPITHELIAL-CELLS; CYTOCHROME-C; BACTERIAL PATHOGENS; BCL-2; ACTIVATION; PROTEIN; INHIBITION; RELEASE AB Porphyromonas gingivalis, a Gram-negative oral anaerobe, is associated with periodontal diseases that, in some form, affect up to 80% of the U. S. population. The organism is highly proteolytic, and noncatalytic adhesin domains of the major proteases, gingipains, are involved in bacterium-host interactions. Recently, we showed that gingipain adhesin peptide A44 hijacks the host's clathrin-dependent endocytosis system, allowing the peptide and whole bacteria to be internalized by epithelial cells. In the present study, we found by cell fractionation assays and confocal microscopy that peptide A44 translocated to host mitochondria. Cell viability assays and quantitative real-time PCR showed that the peptide interacted with the cell death machinery by triggering upregulation of antiapoptotic factors bcl-2 and bcl-XL and prevented staurosporine-induced apoptosis for up to 12 h. We confirmed these findings with Western blot analyses of caspase-9 activation in time course experiments with staurosporine. Finally, we verified a similar antiapoptotic effect for P. gingivalis, showing for the first time that the organism manipulated mitochondrial functions during the first hours of infection, thus resisting host cell clearance by apoptosis of infected cells. This mechanism may enable the bacteria to persist in the protected cellular environment until the next step in pathogenesis, progression or resolution of infection. C1 [Boisvert, Heike; Duncan, Margaret J.] Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Boisvert, H (reprint author), Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. EM hboisvert@forsyth.org FU U.S. National Institutes of Health [R01-DE015931, T32-DE007327-08] FX This work was supported by U.S. National Institutes of Health grants R01-DE015931 and T32-DE007327-08. NR 48 TC 9 Z9 9 U1 0 U2 2 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 AUG PY 2010 VL 78 IS 8 BP 3616 EP 3624 DI 10.1128/IAI.00187-10 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 626TQ UT WOS:000279990400030 PM 20547744 ER PT J AU Lipsky, BA Kollef, MH Miller, LG Sun, XW Johannes, RS Tabak, YP AF Lipsky, Benjamin A. Kollef, Marin H. Miller, Loren G. Sun, Xiaowu Johannes, Richard S. Tabak, Ying P. TI Predicting Bacteremia among Patients Hospitalized for Skin and Skin-Structure Infections: Derivation and Validation of a Risk Score SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID SOFT-TISSUE INFECTIONS; RESISTANT STAPHYLOCOCCUS-AUREUS; BLOOD-STREAM INFECTION; INADEQUATE ANTIMICROBIAL TREATMENT; INAPPROPRIATE ANTIBIOTIC-THERAPY; INTENSIVE-CARE-UNIT; LARGE US DATABASE; ADULT PATIENTS; NEEDLE ASPIRATION; CELLULITIS AB OBJECTIVE. Bacteremia is relatively common in patients with skin and skin-structure infection (SSSI) severe enough to require hospitalization. We used selected demographic and clinical characteristics easily assessable at initial evaluation to develop a model for the early identification of patients with SSSI who are at higher risk for bacteremia. PARTICIPANTS. A large database of adults hospitalized with SSSI at 97 hospitals in the United States during the period from 2003 through 2007 and from whom blood samples were obtained for culture at admission. METHODS. We compared selected candidate predictor variables for patients shown to have bacteremia and patients with no demonstrated bacteremia. Using stepwise logistic regression to identify independent risk factors for bacteremia, we derived a model by using 75% of a randomly split cohort, converted the model coefficients into a risk score system, and then we validated it by using the remaining 25% of the cohort. RESULTS. Bacteremia was documented in 1,021 (11.7%) of the 8,747 eligible patients. Independent predictors of bacteremia (P < .001) were infected device or prosthesis, respiratory rate less than 10 or more than 29 breaths per minute, pulse rate less than 49 or more than 125 beats per minute, temperature less than 35.6 degrees C or at least 38.0 degrees C, white blood cell band percentage of 7% or more, white blood cell count greater than 11 x 10(9)/L, healthcare-associated infection, male sex, and older age. The bacteremia rates ranged from 3.7% (lowest decile) to 30.6% (highest decile) (P < .001). The model C statistic was 0.71; the Hosmer-Lemeshow test P value was .36, indicating excellent model calibration. CONCLUSIONS. Using data available at hospital admission, we developed a risk score that differentiated SSSI patients at low risk for bacteremia from patients at high risk. This score may help clinicians identify patients who require more intensive monitoring or antimicrobial regimens appropriate for treating bacteremia. Infect Control Hosp Epidemiol 2010; 31(8): 828-837 C1 [Lipsky, Benjamin A.] VA Puget Sound Hlth Care Syst, Primary Care Clin S 111 PCC, Gen Med Serv, Seattle, WA 98108 USA. [Lipsky, Benjamin A.] Univ Washington, Dept Med, Seattle, WA USA. [Kollef, Marin H.] Washington Univ, Sch Med, St Louis, MO USA. [Miller, Loren G.] UCLA Sch Med, Los Angeles, CA USA. [Miller, Loren G.] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Sun, Xiaowu; Johannes, Richard S.; Tabak, Ying P.] CareFusion, MedMined Serv, Clin Res, Marlborough, MA USA. [Johannes, Richard S.] Harvard Univ, Sch Med, Boston, MA USA. RP Lipsky, BA (reprint author), VA Puget Sound Hlth Care Syst, Primary Care Clin S 111 PCC, Gen Med Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. EM balipsky@uw.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 FU CareFusion Corporation; Cubis; Pfizer FX We thank CareFusion Clinical Research team members Karen Derby, Vikas Gupta, and Linda Hyde for their contributions in database management, analysis, and technical and administrative support. Editorial support was provided by Hamilton House, Virginia Beach, Virginia, and funded by CareFusion Corporation.; B. A. L. reports that he has served as a consultant to Cubist, Pfizer, Merck, Wyeth-Ayerst, and Ortho-McNeil. M. H. K. reports that he has been a member of the the speakers' bureau or served as a consultant for Astrazeneca, Pfizer, Merck, Elan, Bard, and Kimberly-Clark and has served as a consultant for Astellas, Cubist, and Bayer. L. G. M. reports that he has received research grants from Cubist and Pfizer and served as a consultant to Theravance. X. S., R.S.J., and Y.P.T. report that they are employees of CareFusion Corporation. NR 36 TC 10 Z9 10 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD AUG PY 2010 VL 31 IS 8 BP 828 EP 837 DI 10.1086/654007 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 621SC UT WOS:000279601800009 PM 20586653 ER PT J AU Cullen, G Sands, BE Yajnik, V AF Cullen, Garret Sands, Bruce E. Yajnik, Vijay TI Babesiosis in a Patient on Infliximab for Crohn's Disease SO INFLAMMATORY BOWEL DISEASES LA English DT Letter ID MALARIA C1 [Cullen, Garret; Sands, Bruce E.; Yajnik, Vijay] Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. RP Cullen, G (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD AUG PY 2010 VL 16 IS 8 BP 1269 EP 1270 DI 10.1002/ibd.21158 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 640TZ UT WOS:000281077400002 PM 19885904 ER PT J AU Herfarth, HH Osterman, MI Isaacs, KL Lewis, JD Sands, BE AF Herfarth, Hans H. Osterman, Mark I. Isaacs, Kim L. Lewis, James D. Sands, Bruce E. TI Efficacy of Methotrexate in Ulcerative Colitis: Failure or Promise SO INFLAMMATORY BOWEL DISEASES LA English DT Review DE methotrexate; ulcerative colitis; inflammatory bowel disease ID INFLAMMATORY-BOWEL-DISEASE; LOW-DOSE METHOTREXATE; ISRAELI MULTICENTER TRIAL; PEDIATRIC CROHNS-DISEASE; OF-THE-LITERATURE; RHEUMATOID-ARTHRITIS; ORAL METHOTREXATE; DOUBLE-BLIND; PARENTERAL METHOTREXATE; MAINTAINING REMISSION AB Background: Low-dose methotrexate is a widely used and efficacious therapy in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. Prospective randomized controlled trials have demonstrated the efficacy of parenteral methotrexate in Crohn's disease (CD). We performed a systematic review of the efficacy of methotrexate in ulcerative colitis (UC) and discuss the results in the context of the known pharmacokinetics and adverse events of methotrexate therapy in inflammatory bowel diseases and other inflammatory conditions. Materials and Methods: We performed a systematic review of the literature in Medline, Embase, and Web of Science. All publications describing patients with UC treated with methotrexate were included. Results: We identified 12 studies or retrospective case series and 5 meeting abstracts that met the inclusion criteria. Only I study reported a prospective randomized placebo-controlled trial using methotrexate at a dose of 12.5 mg orally with no significant clinical benefit. However, the majority of uncontrolled retrospective analyses suggest a clinical response to methotrexate therapy in a range of 30%-80% when the drug is applied by parenteral route in doses between 20-25 mg. Conclusions: The only randomized controlled trial of methotrexate in UC employed oral dosing and doses lower than those shown to be effective in CD and did not demonstrate efficacy, whereas uncontrolled, retrospective studies using doses and routes of administration similar to those employed in CD suggest benefit. Well-designed, prospective, placebo-controlled trials of methotrexate in UC are needed. C1 [Herfarth, Hans H.] Univ N Carolina, Div Gastroenterol & Hepatol, Dept Med, Chapel Hill, NC 27599 USA. [Osterman, Mark I.; Lewis, James D.] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Osterman, Mark I.; Lewis, James D.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Sands, Bruce E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Crohns & Colitis Ctr, Boston, MA USA. [Sands, Bruce E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. RP Herfarth, HH (reprint author), Univ N Carolina, Div Gastroenterol & Hepatol, Dept Med, Bioinformat Bldg,CB 7080, Chapel Hill, NC 27599 USA. EM hherf@med.unc.edu FU National Institutes of Health [1U34DK084511-01]; Crohn's and Colitis Foundation of America (CCFA) FX Drs. Herfarth, Isaacs, Lewis, Osterman, and Sands are supported by a National Institutes of Health grant 1U34DK084511-01 and the Crohn's and Colitis Foundation of America (CCFA). NR 60 TC 16 Z9 18 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD AUG PY 2010 VL 16 IS 8 BP 1421 EP 1430 DI 10.1002/ibd.21246 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 640TZ UT WOS:000281077400023 PM 20186931 ER PT J AU Leatherman, S Ferris, TG Berwick, D Omaswa, F Crisp, N AF Leatherman, Sheila Ferris, Timothy G. Berwick, Donald Omaswa, Francis Crisp, Nigel TI The role of quality improvement in strengthening health systems in developing countries SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE quality improvement; healthcare systems; healthcare systems; developing countries ID RESOURCE-POOR SETTINGS; IMMUNIZATION COVERAGE; CARES EXPERIENCES; OBSTETRIC CARE; SOUTH-AFRICA; MANAGEMENT; SERVICES; RWANDA; PERFORMANCE; ADHERENCE AB Quality of care was recognized as a key element for improved health outcomes and efficiency in the World Health Organization's (WHO) widely adopted framework for health system strengthening in resource-poor countries. Although modern approaches to improving quality are increasingly used globally, their adoption remains sporadic in developing countries. Healthcare leaders and improvement experts representing 15 countries met in October 2008 to catalyze the adoption of quality improvement (QI) methods to improve healthcare quality in resource-poor settings. This paper describes the evidence used to frame deliberations, the proceedings and a proposal for incorporating QI methods into plans for strengthening health systems. The conference participants presented case reports and reviewed a growing body of evidence from peer-reviewed journals demonstrating that QI methods can make significant contributions in resource poor settings. Deliberations focused on the barriers to adoption of QI methods and potential strategies for addressing those barriers. Attendees concluded that QI has the potential to optimize the use of limited resources available from governments and global initiatives targeted at achieving shared aims. Demonstrable improvements in quality may encourage greater investment in health systems in developing countries by increasing donor, population and governmental confidence that resources are being used well. C1 [Ferris, Timothy G.] Mass Gen Hosp, Boston, MA USA. [Leatherman, Sheila] Univ N Carolina, Sch Publ Hlth, London Sch Econ, Minneapolis, MN USA. [Berwick, Donald; Crisp, Nigel] Inst Healthcare Improvement, Cambridge, MA USA. [Omaswa, Francis] African Ctr Global Hlth & Social Transformat, Kampala, Uganda. RP Ferris, TG (reprint author), Massachusetts Gen Phy Org, 55 Fruit St,Bulfinch 205E, Boston, MA 02114 USA. EM tferris@partners.org FU Institute for Healthcare Improvement and The Rockefeller Foundation FX The authors would also like to acknowledge the Institute for Healthcare Improvement and The Rockefeller Foundation for their joint support in hosting the October 2008 meeting in Bellagio. NR 42 TC 53 Z9 54 U1 1 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD AUG PY 2010 VL 22 IS 4 BP 237 EP 243 DI 10.1093/intqhc/mzq028 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 630MT UT WOS:000280278200001 PM 20543209 ER PT J AU Schartel, J Mori, DL AF Schartel, Janell Mori, DeAnna L. TI THE RELATIONSHIP OF ANXIETY TO MULTIPLE ASPECTS OF TREATMENT ADHERENCE IN PATIENTS WITH ESRD SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Schartel, Janell] VA Boston Healthcare Syst, Boston, MA USA. [Mori, DeAnna L.] Boston Univ, Sch Med, Boston, MA 02118 USA. EM janell.schartel@va.gov 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 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 2 EP 3 PG 2 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500002 ER PT J AU Campbell, MK Rosenstien, D Jones, A Andersen, B Syrjala, K Baker, S Miller, K Jacobs, L McCabe, M Ganz, P Gellin, M Tessaro, I Manning, M AF Campbell, Marci K. Rosenstien, Donald Jones, Alison Andersen, Barbara Syrjala, Karen Baker, Scott Miller, Kenneth Jacobs, Linda McCabe, Mary Ganz, Patricia Gellin, Mindy Tessaro, Irene Manning, Michelle TI CREATING A SURVIVORSHIP PROGRAM-WHAT DOES IT TAKE TO BE SUCCESSFUL? SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Campbell, Marci K.; Rosenstien, Donald; Gellin, Mindy; Tessaro, Irene; Manning, Michelle] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hll, NC 27599 USA. [Jacobs, Linda] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Miller, Kenneth] Dana Farber Canc Inst, Boston, MA 02115 USA. [Syrjala, Karen; Baker, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [McCabe, Mary] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Andersen, Barbara] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Andersen, Barbara] Solove Res Inst, Columbus, OH USA. [Ganz, Patricia] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Jones, Alison] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. EM mindy_gellin@med.unc.edu 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 1070-5503 J9 INT J BEHAV MED JI Int. J. Behav. Med. PD AUG PY 2010 VL 17 SU 1 BP 325 EP 326 PG 2 WC Psychology, Clinical SC Psychology GA 628BG UT WOS:000280088500734 ER PT J AU Fischer, SEJ AF Fischer, Sylvia E. J. TI Small RNA-mediated gene silencing pathways in C. elegans SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE RNAi; miRNA; siRNA; Silencing; C. elegans ID DOUBLE-STRANDED-RNA; TRANSMEMBRANE PROTEIN SID-1; CAENORHABDITIS-ELEGANS; MESSENGER-RNA; REGULATORY RNA; POSTTRANSCRIPTIONAL REGULATION; MICROPROCESSOR COMPLEX; MICRORNA PRECURSORS; SLICER ACTIVITY; GW182 PROTEINS AB Small RNA pathways, including the RNA interference (RNAi) pathway and the microRNA (miRNA) pathway, regulate gene expression, defend against transposable elements and viruses, and, in some organisms, guide genome rearrangements. The nematode Caenorhabditis elegans (C. elegans) has been at the forefront of small RNA research; not only were the first miRNAs and their function as regulators of gene expression discovered in C elegans, but also double-stranded RNA-induced gene silencing by RNAi was discovered in this model organism. Since then, genetic and RNAi-mediated screens, candidate gene approaches, and biochemical studies have uncovered numerous factors in the small RNA pathways and painted a rich palette of interacting pathways. Here we review the different small RNAs that have been discovered in C. elegans and discuss our understanding of their biogenesis pathways and mechanisms of action. (C) 2010 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Fischer, SEJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, 185 Cambridge St, Boston, MA 02114 USA. EM fischer@molbio.mgh.harvard.edu NR 113 TC 31 Z9 32 U1 1 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD AUG PY 2010 VL 42 IS 8 BP 1306 EP 1315 DI 10.1016/j.biocel.2010.03.006 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 631XN UT WOS:000280384100012 PM 20227516 ER PT J AU Kuan, CT Srivastava, N McLendon, RE Marasco, WA Zalutsky, MR Bigner, DD AF Kuan, Chien-Tsun Srivastava, Nidhi McLendon, Roger E. Marasco, Wayne A. Zalutsky, Michael R. Bigner, Darell D. TI Recombinant single-chain variable fragment antibodies against extracellular epitopes of human multidrug resistance protein MRP3 for targeting malignant gliomas SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE GBM; MRP3; scFv antibody; phage display ID SOLID TUMORS; STEM-CELLS; RAT-LIVER; EXPRESSION; HETEROGENEITY; TRANSPORTERS; IMMUNIZATION; XENOGRAFTS; MARKERS AB Multidrug resistance protein 3 (MRP3), a multidrug resistance protein identified by serial analysis of gene expression as a glioblastoma multiforme (GBM)-associated molecule, is highly expressed in GBM, but not in normal brain cells. Thus, MRP3 is a candidate for GBM immunotargeting, but to date, no monoclonal antibody has been isolated that can target an extracellular MRP3 epitope. By phage display, we have isolated 3 recombinant, fully human, single-chain Fv (scFv) antibodies, M25, M58 and M89, which specifically react with the extracellular N-terminus of human MRP3. In ELISA, these scFvs reacted only with the peptide used for screening and not with other MRP3-derived peptides. Flow cytometric analysis revealed that these scFv fragments bind specifically to viable human GBM cells displaying different MRP3 expression levels, but not to MRP3-null cells. Furthermore, these scFv antibodies failed to react with tumor cells overexpressing other MRP proteins, including MRP1, MRP2, MRP4 and MRP5. M25 and M58 also bound to viable neurospheres. lodogen-labeled scFvs demonstrated a yield of 56-76%. The immunoreactive fractions of the radiolabeled M25, M58 and M89 scFvs were 32, 52 and 69%, respectively. M25 exhibited 20% internalization into D2159MG neurospheres, M58, 33% into D54MG cells and M89, 26% into D247MG. Immunohistochemical evaluation of human gliomas to determine the localization of MRP3 antigen using scFvs M25 and M58 showed a dense cytoplasmic and membranous staining pattern. These Fv-based recombinant antibodies, which possess superior tumor penetration capabilities and selectively target tumor cells that express MRP3, may potentially be used in immunotherapy and diagnosis for brain tumors and other cancers. C1 [Kuan, Chien-Tsun; Srivastava, Nidhi; McLendon, Roger E.; Bigner, Darell D.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Kuan, Chien-Tsun; Srivastava, Nidhi; McLendon, Roger E.; Bigner, Darell D.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA. [Marasco, Wayne A.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Zalutsky, Michael R.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. RP Kuan, CT (reprint author), Duke Univ, Med Ctr, Dept Pathol, Box 3156, Durham, NC 27710 USA. EM kuan@duke.edu; bigne001@mc.duke.edu FU NIH, National Center for Research Resources [MO1 RR30]; NINDS [5P50 NS20023]; NCI SPORE [5P50 CA 108786, CA 74886]; NIH [R37 CA 011898]; Finding Cures for Glioma Grants FX Grant sponsor: NIH (General Clinical Research Centers Program, National Center for Research Resources); Grant number: MO1 RR30; Grant sponsor: NINDS; Grant number: 5P50 NS20023; Grant sponsor: NCI SPORE; Grant numbers: 5P50 CA 108786, CA 74886; Grant sponsor: NIH Merit Award; Grant number: R37 CA 011898; Grant sponsor: Finding Cures for Glioma Grants NR 47 TC 12 Z9 15 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 1 PY 2010 VL 127 IS 3 BP 598 EP 611 DI 10.1002/ijc.25062 PG 14 WC Oncology SC Oncology GA 615JP UT WOS:000279131300011 PM 19937796 ER PT J AU Campos, SM Berlin, ST Parker, LM Chen, WY Bunnell, CA Atkinson, T Lee, J Matulonis, U Hirsch, MS Harris, L Krasner, CN AF Campos, Susana M. Berlin, Suzanne T. Parker, Leroy M. Chen, Wendy Y. Bunnell, Craig A. Atkinson, Tina Lee, Julie Matulonis, Ursula Hirsch, Michelle S. Harris, Lyndsay Krasner, Carolyn N. TI Phase I trial of liposomal doxorubicin and ZD1839 in patients with refractory gynecological malignancies or metastatic breast cancer SO INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY LA English DT Article DE ZD1839; Liposomal doxorubicin; Breast cancer; Gynecological cancer; Toxicity ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; ADVANCED OVARIAN-CANCER; PLATINUM-RESISTANT OVARIAN; FACTOR RECEPTOR; III TRIAL; MONOCLONAL-ANTIBODY; MULTICENTER TRIAL; ORAL ETOPOSIDE AB Pegylated liposomal doxorubicin has activity in both breast and ovarian cancer. Preclinical data noted that ZD1839 acts synergistically with chemotherapy. Given the lack of cross-resistance between these two agents, a phase I trial was initiated examining the safety and efficacy of the combination of liposomal doxorubicin and ZD1839 in patients with recurrent gynecologic or metastatic breast cancer. Dose-limiting toxicity (DLT) was defined within the first two cycles of treatment. Escalating doses of liposomal doxorubicin were administered every 4 weeks with ZD1839. Pharmacokinetic analysis and correlative studies were performed. Thirty-five patients were enrolled in this study: six in each cohort. One DLT (febrile neutropenia) was observed in cohort 2. Dose level 3 was determined to be the maximum tolerated dose (MTD), and an additional ten patients were accrued. Serious adverse events (SAEs) included one patient with mental status changes believed secondary to disease progression and two central nervous system (CNS) bleeds believed to be unrelated to the combination of study agents. Toxicities were generally mild except for skin and gastrointestinal toxicity. No cardiac toxicity was observed. The best response to therapy included four partial responses and 20 patients with stable disease. Liposomal doxorubicin with ZD1839 is an active regimen but is associated with increased skin toxicity in patients with advanced breast and gynecologic cancer. C1 [Campos, Susana M.; Berlin, Suzanne T.; Atkinson, Tina; Lee, Julie; Matulonis, Ursula] Dana Farber Canc Inst, Dept Gynecol Oncol, Boston, MA 02115 USA. [Parker, Leroy M.; Chen, Wendy Y.; Bunnell, Craig A.] Dana Farber Canc Inst, Dept Breast Oncol, Boston, MA 02115 USA. [Krasner, Carolyn N.] Massachusetts Gen Hosp, Dept Gynecol Oncol, Boston, MA 02114 USA. [Hirsch, Michelle S.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Harris, Lyndsay] Yale Univ, Dept Med Oncol, New Haven, CT USA. RP Campos, SM (reprint author), Dana Farber Canc Inst, Dept Gynecol Oncol, 44 Binney St, Boston, MA 02115 USA. EM scampos@partners.org FU Ortho-Biotech; AstraZeneca; Genentech FX Susana M. Campos serves as a medical consultant to Genentech, Inc, and GSK, Inc. and has received research funding from Ortho-Biotech, AstraZeneca and Genentech. Ursula Matulonis has received research funding from AstraZeneca. NR 59 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER JAPAN KK PI TOKYO PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065, JAPAN SN 1341-9625 EI 1437-7772 J9 INT J CLIN ONCOL JI Int. J. Clin. Oncol. PD AUG PY 2010 VL 15 IS 4 BP 390 EP 398 DI 10.1007/s10147-010-0073-6 PG 9 WC Oncology SC Oncology GA 637HZ UT WOS:000280809500009 PM 20405155 ER PT J AU Sala, E DeSouza, N Lee, SI Atri, M Hricak, H AF Sala, Evis DeSouza, Nandita Lee, Susanna I. Atri, Mostafa Hricak, Hedvig CA Gynaecological Canc InterGrp TI Ovarian Cancer The Role of Functional Imaging as an End Point in Clinical Trials SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Ovarian cancer; Functional imaging; Biomarker; Clinical trial ID APPARENT DIFFUSION-COEFFICIENT; POSITRON-EMISSION-TOMOGRAPHY; DIAGNOSTIC ONCOLOGY GROUP; CONTRAST-ENHANCED MRI; COMPUTED-TOMOGRAPHY; PET-CT; PERITONEAL CARCINOMATOSIS; NEOADJUVANT CHEMOTHERAPY; 2ND-LOOK LAPAROTOMY; PREDICTING RESPONSE AB The Gynaecological Cancer InterGroup conducts collaborative trials in gynecologic cancer and also aims to develop standards that can be used to strengthen all aspects of study methodology. There is an urgent need to develop more refined imaging end points that can be used as early treatment response biomarkers in ovarian cancer. Therefore, the Gynaecological Cancer InterGroup commissioned an expert position paper on the role of functional imaging as an end point in clinical trials in ovarian cancer. In this position paper, we state the limitation of current anatomical imaging methods used in clinical trials, highlight the potential of functional imaging, and provide key recommendations on the use of functional imaging as an end point in ovarian cancer clinical trials. C1 [Sala, Evis] Addenbrookes Hosp, Dept Radiol, Cambridge CB2 0QQ, England. [DeSouza, Nandita] Inst Canc Res, Surrey, England. [DeSouza, Nandita] Royal Marsden Hosp, Surrey, England. [Lee, Susanna I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Atri, Mostafa] Univ Toronto, Abdominal Div, Toronto, ON M5S 1A1, Canada. [Hricak, Hedvig] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. RP Sala, E (reprint author), Addenbrookes Hosp, Dept Radiol, Box 218,Hills Rd, Cambridge CB2 0QQ, England. EM es220@radiol.cam.ac.uk RI 李, 海明/I-2405-2012 NR 79 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD AUG PY 2010 VL 20 IS 6 BP 971 EP 978 DI 10.1111/IGC.0b013e3181e0a353 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 634HR UT WOS:000280572000010 PM 20683404 ER PT J AU Righi, V Apidianakis, Y Mintzopoulos, D Astrakas, L Rahme, LG Tzika, AA AF Righi, Valeria Apidianakis, Yiorgos Mintzopoulos, Dionyssios Astrakas, Loukas Rahme, Laurence G. Tzika, A. Aria TI In vivo high-resolution magic angle spinning magnetic resonance spectroscopy of Drosophila melanogaster at 14.1 T shows trauma in aging and in innate immune-deficiency is linked to reduced insulin signaling SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE magnetic resonance spectroscopy; high resolution magic angle spinning; total through bond correlation spectroscopy; Drosophila melanogaster; biomarkers; immunity; insulin signaling; obesity; aging ID INTRAMYOCELLULAR LIPID-CONTENT; RESISTANCE FOLLOWING INJURY; PROTON NMR-SPECTROSCOPY; SKELETAL-MUSCLE; FATTY-ACIDS; INDUCED APOPTOSIS; RELAXATION-TIMES; BURN-TRAUMA; METABOLISM; H-1 AB In vivo magnetic resonance spectroscopy (MRS), a non-destructive biochemical tool for investigating live organisms, has yet to be used in the fruit fly Drosophila melanogaster, a useful model organism for investigating genetics and physiology. We developed and implemented a high-resolution magic-angle-spinning (HRMAS) MRS method to investigate live Drosophila at 14.1 T. We demonstrated, for the first time, the feasibility of using HRMAS MRS for molecular characterization of Drosophila with a conventional MR spectrometer equipped with an HRMAS probe. We showed that the metabolic HRMAS MRS profiles of injured, aged wild-type (wt) flies and of immune deficient (imd) flies were more similar to chico flies mutated at the chico gene in the insulin signaling pathway, which is analogous to insulin receptor substrate 1-4 (IRS1-4) in mammals and less to those of adipokinetic hormone receptor (akhr) mutant flies, which have an obese phenotype. We thus provide evidence for the hypothesis that trauma in aging and in innate immune-deficiency is linked to insulin signaling. This link may explain the mitochondrial dysfunction that accompanies insulin resistance and muscle wasting that occurs in trauma, aging and immune system deficiencies, leading to higher susceptibility to infection. Our approach advances the development of novel in vivo non-destructive research approaches in Drosophila, suggests biomarkers for investigation of biomedical paradigms, and thus may contribute to novel therapeutic development. C1 [Righi, Valeria; Apidianakis, Yiorgos; Mintzopoulos, Dionyssios; Astrakas, Loukas; Tzika, A. Aria] Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Surg Lab,Dept Surg, Boston, MA 02114 USA. [Righi, Valeria; Apidianakis, Yiorgos; Mintzopoulos, Dionyssios; Astrakas, Loukas; Tzika, A. Aria] Harvard Univ, Sch Med, Shriners Burn Inst, Boston, MA 02114 USA. [Righi, Valeria; Mintzopoulos, Dionyssios; Astrakas, Loukas; Tzika, A. Aria] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Apidianakis, Yiorgos; Rahme, Laurence G.] Massachusetts Gen Hosp, Dept Surg, Mol Surg Lab, Boston, MA 02114 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Surg Lab,Dept Surg, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@hms.harvard.edu RI Astrakas, Loukas/F-5918-2011; OI Apidianakis, Yiorgos/0000-0002-7465-3560; Righi, Valeria/0000-0003-2394-8462 FU National Institute Institutes of Health (NIH) [P50GM021700, AI063433]; Shriner's Hospital for Children [8893] FX This work was supported in part by a National Institute Institutes of Health (NIH) Center Grant (no. P50GM021700) to Ronald G. Tompkins (A. Aria Tzika, Director of the NMR core), NIH grant no. AI063433 to Laurence G. Rahme and a Shriner's Hospital for Children research grant (no. 8893) to A. Aria Tzika. We thank Ovidiu Andronesi Ph.D. for assistance with the TOBSY pulse sequence. We also thank Ann Power Smith Ph.D. of Write Science Right for editorial assistance. NR 82 TC 10 Z9 10 U1 2 U2 14 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD AUG PY 2010 VL 26 IS 2 BP 175 EP 184 DI 10.3892/ijmm_00000450 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 628JO UT WOS:000280115900002 PM 20596596 ER PT J AU Ademi, Z Walls, HL Peeters, A Liew, D Hollingsworth, B Stevenson, C Steg, PG Bhatt, DL Reid, CM AF Ademi, Z. Walls, H. L. Peeters, A. Liew, D. Hollingsworth, B. Stevenson, C. Steg, Ph-G Bhatt, D. L. Reid, C. M. CA REACH Registry Investigators TI Economic implications of obesity among people with atherothrombotic disease SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE atherothrombosis; direct health-care costs; pharmaceuticals ID HEALTH-CARE COSTS; BODY-MASS INDEX; CARDIOVASCULAR RISK-FACTORS; SERVICES USE; INDIVIDUALS; PREVALENCE; AUSTRALIA AB Objective: The purpose of this study was to ascertain the impact of obesity on the cost of disease management in people with or at high risk of atherothrombotic disease from a governmental perspective using a bottom-up approach to cost estimation. In addition, the aim was also to explore the causes of any differences found. Method: The health-care costs of obesity were estimated from 2819 participants recruited into the nationwide Australian REACH Registry with established atherothrombotic disease or at least three risk factors for atherothrombosis. Enrollment was in 2004, through primary care general practices. Information was collected on the use of cardiovascular drugs, hospitalizations and ambulatory care services. 'Bottom-up' costing was undertaken by assigning unit costs to each health-care item, based on Australian Government-reimbursed figures 2006-2007. Linear-mixed models were used to estimate associations between direct medical costs and body mass index (BMI) categories. Results: Annual pharmaceutical costs per person increased with increasing BMI category, even after adjusting for gender, age, living place, formal education, smoking status, hypertension and diabetes. Adjusted annual pharmaceutical costs of overweight and obese participants were higher ($7 (P = 0.004) and $144 (<0.001), respectively) than those of the normal weight participants. This was due to participants in higher BMI categories receiving more pharmaceuticals than normal weight participants. There was no significant change across the BMI categories in annual ambulatory care costs and annual hospital costs. Conclusion: In these participants with or at high risk of atherothrombotic disease, annual pharmaceutical costs were greater in participants of higher BMI category, but there was not such a gradient in the annual hospital or ambulatory care costs. The greater cardiovascular pharmaceutical costs for participants of higher BMI categories remained even after adjusting for a range of demographic factors and comorbidities. Our results suggest that these costs are explained by the higher number of drugs used among people with atherothrombotic disease. Further investigation is needed to understand the reasons for this level of drug use. International Journal of Obesity (2010) 34, 1284-1292; doi: 10.1038/ijo.2010.42; published online 2 March 2010 C1 [Ademi, Z.; Walls, H. L.; Peeters, A.; Stevenson, C.; Reid, C. M.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Liew, D.] Univ Melbourne, Dept Med, St Vincents Hosp, Melbourne, Vic 3010, Australia. [Hollingsworth, B.] Monash Univ, Ctr Hlth Econ, Melbourne, Vic 3004, Australia. [Steg, Ph-G] Univ Paris 07, INSERM, U698, AP HP, Paris, France. [Bhatt, D. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, D. L.] VA Boston Healthcare Syst, Boston, MA USA. RP Ademi, Z (reprint author), Monash Univ, Dept Epidemiol & Prevent Med, Sch Publ Hlth & Prevent Med, Alfred Hosp, Commercial Rd, Melbourne, Vic 3004, Australia. EM Zanfina.Ademi@med.monash.edu.au RI Peeters, Anna/B-3663-2013; OI Hollingsworth, Bruce/0000-0002-4314-6523; Liew, Danny/0000-0002-0131-623X FU sanofi-aventis; Bristol-Myers Squibb; Waksman Foundation (Tokyo, Japan); Monash University; Australian Research Council [LP077532]; National Health and Medical Research Council [465130] FX Zanfina Ademi, Helen Walls, Anna Peteers, Danny Liew, Bruce Hollingsworth, Christopher Stevenson and Christopher Reid declare no conflict of interest. Ph Gabriel Steg has the following disclosures: research grant from sanofi-aventis. Speakers bureau: Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Nycomed, sanofi-aventis, Servier. Consulting/advisory board: Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Endotis, GlaxoSmithKline, Medtronic, MSD, Nycomed, sanofi-aventis, Servier, The Medicines Company. Deepak L Bhatt has received research grants from sanofi-aventis and Bristol-Myers Squibb who have funded the REACH Registry. He has also received institutional research support from AstraZeneca, Eisai, Ethicon, Heartscape and The Medicines Company.; The global REACH Registry is sponsored by sanofi-aventis, Bristol-Myers Squibb, and the Waksman Foundation (Tokyo, Japan), and is endorsed by the World Heart Federation. The REACH Registry enforces a no-ghostwriting policy. A complete list of global REACH investigators is available at www.reachregistry.org. This work was supported by Monash University. In addition, this work was supported in part by the Australian Research Council Linkage Project LP077532, National Health and Medical Research Council grant (No. 465130). NR 25 TC 3 Z9 3 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD AUG PY 2010 VL 34 IS 8 BP 1284 EP 1292 DI 10.1038/ijo.2010.42 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 636KK UT WOS:000280732400007 PM 20195286 ER PT J AU Wynn, JK Horan, WP Kring, AM Simons, RF Green, MF AF Wynn, Jonathan K. Horan, William P. Kring, Ann M. Simons, Robert F. Green, Michael F. TI Impaired anticipatory event-related potentials in schizophrenia SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE Schizophrenia; Event-related potentials (ERP); Anticipation ID STIMULUS-PRECEDING NEGATIVITY; STRIATAL REWARD PREDICTION; SLOW BRAIN POTENTIALS; PHYSICAL ANHEDONIA; FEEDBACK STIMULI; HEART-RATE; TASK; INFORMATION; DYSFUNCTION; PLEASURE AB Deficits in anticipation are implicated across a variety of cognitive and emotional processes in schizophrenia. Although diminished anticipatory event-related potentials (ERPs) have been detected during tasks requiring motor response preparation in schizophrenia, no prior ERP study has examined non-motor-related anticipatory processes or used motivationally engaging stimuli. Thirty-four schizophrenia outpatients and 36 healthy controls completed a cued, reaction-time contingent picture viewing task to assess two types of anticipatory ERPs, one involving motor response preparation (Contingent Negative Variation [CNV]) and one not involving motor preparation (Stimulus Preceding Negativity [SPN]). The ERP paradigm included emotional and non-emotional pictures, and participants also completed trait anhedonia questionnaires. Patients and controls demonstrated similar patterns of reaction time and self-reported emotional responses to the pictures. However, patients demonstrated generally lower CNV and SPN across pleasant, neutral, and unpleasant picture conditions. Patients also reported lower anticipatory pleasure than controls on a trait questionnaire. Schizophrenia patients demonstrate diminished motor- and non-motor-related anticipatory processing, which may have wide-ranging adverse functional consequences. Published by Elsevier B.V. C1 [Wynn, Jonathan K.; Horan, William P.; Green, Michael F.] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Kring, Ann M.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Simons, Robert F.] Univ Delaware, Newark, DE 19716 USA. RP Wynn, JK (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, MIRECC 210A,Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIMH NIH HHS [R01 MH043292, R01 MH043292-19, R01 MH065707, R01 MH065707-05, R03 MH077141, R03 MH077141-01] NR 59 TC 24 Z9 28 U1 3 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD AUG PY 2010 VL 77 IS 2 BP 141 EP 149 DI 10.1016/j.ijpsycho.2010.05.009 PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 633WZ UT WOS:000280539000008 PM 20573584 ER PT J AU D'Amico, AV Braccioforte, MH Moran, BJ Chen, MH AF D'Amico, Anthony V. Braccioforte, Michelle H. Moran, Brian J. Chen, Ming-Hui TI CAUSES OF DEATH IN MEN WITH PREVALENT DIABETES AND NEWLY DIAGNOSED HIGH- VERSUS FAVORABLE-RISK PROSTATE CANCER SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Diabetes; prostate cancer; cause of death ID ANDROGEN DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY; RADIATION-THERAPY; COMPETING RISK; RADIOTHERAPY; MORTALITY; SURVIVAL; ADJUVANT; BRACHYTHERAPY AB Purpose: To determine whether prevalent diabetes mellitus (pDM) affects the presentation, extent of radiotherapy, or prostate cancer (PCa)-specific mortality (PCSM) and whether PCa aggressiveness affects the risk of non-PCSM, DM-related mortality, and all-cause mortality in men with pDM. Methods: Between October 1997 and July 2907, 5,279 men treated at the Chicago Prostate Cancer Center with radiotherapy for PCa were included in the study. Logistic and competing risk regression analyses were performed to assess whether pDM was associated with high-grade PCa, less aggressive radiotherapy, and an increased risk of PCSM. Competing risks and Cox regression analyses were performed to assess whether PCa aggressiveness described by risk group in men with pDM was associated with the risk of non-PCSM, DM-related mortality, and all-cause mortality. Analyses were adjusted for predictors of high-grade PCa and factors that could affect treatment extent and mortality. Results: Men with pDM were more likely (adjusted hazard ratio [AHR], 1.9; 95% confidence interval [CI], 1.3-2.7; p = .002) to present with high-grade PCa but were not treated less aggressively (p = .33) and did not have an increased risk of PCSM (p = .58) compared to men without pDM. Among the men with pDM, high-risk PCa was associated with a greater risk of non-PCSM (AHR, 2.2; 95% CI, 1.1-4.5; p = .035), DM-related mortality (AHR, 5.2; 95% CI, 2.0-14.0; p = .001), and all-cause mortality (AHR, 2.4; 95% Cl, 1.2-4.7; p = .01) compared to favorable-risk PCa. Conclusion: Aggressive management of pDM is warranted in men with high-risk PCa. (C) 2010 Elsevier Inc. C1 [D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Braccioforte, Michelle H.; Moran, Brian J.] Prostate Canc Fdn Chicago, Dept Radiat Oncol, Westmont, IL USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@partners.org NR 33 TC 21 Z9 21 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 AUG 1 PY 2010 VL 77 IS 5 BP 1329 EP 1337 DI 10.1016/j.ijrobp.2009.06.051 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 632WJ UT WOS:000280459700007 PM 19879061 ER PT J AU Hachinski, V Donnan, GA Gorelick, PB Hacke, W Cramer, SC Kaste, M Fisher, M Brainin, M Buchan, AM Lo, EH Skolnick, BE Furie, KL Hankey, GJ Kivipelto, M Morris, J Rothwell, PM Sacco, RL Smith, SC Wang, YL Bryer, A Ford, GA Iadecola, C Martins, SCO Saver, J Skvortsova, V Bayley, M Bednar, MM Duncan, P Enney, L Finklestein, S Jones, TA Kalra, L Kleim, J Nitkin, R Teasell, R Weiller, C Desai, B Goldberg, MP Heiss, WD Saarelma, O Schwamm, LH Shinohara, Y Trivedi, B Wahlgren, N Wong, LK Hakim, A Norrving, B Prudhomme, S Bornstein, NM Davis, SM Goldstein, LB Leys, D Tuomilehto, J AF Hachinski, Vladimir Donnan, Geoffrey A. Gorelick, Philip B. Hacke, Werner Cramer, Steven C. Kaste, Markku Fisher, Marc Brainin, Michael Buchan, Alastair M. Lo, Eng H. Skolnick, Brett E. Furie, Karen L. Hankey, Graeme J. Kivipelto, Miia Morris, John Rothwell, Peter M. Sacco, Ralph L. Smith, Sidney C., Jr. Wang, Yulun Bryer, Alan Ford, Gary A. Iadecola, Costantino Martins, Sheila C. O. Saver, Jeff Skvortsova, Veronika Bayley, Mark Bednar, Martin M. Duncan, Pamela Enney, Lori Finklestein, Seth Jones, Theresa A. Kalra, Lalit Kleim, Jeff Nitkin, Ralph Teasell, Robert Weiller, Cornelius Desai, Bhupat Goldberg, Mark P. Heiss, Wolf-Dieter Saarelma, Osmo Schwamm, Lee H. Shinohara, Yukito Trivedi, Bhargava Wahlgren, Nils Wong, Lawrence K. Hakim, Antoine Norrving, Bo Prudhomme, Stephen Bornstein, Natan M. Davis, Stephen M. Goldstein, Larry B. Leys, Didier Tuomilehto, Jaakko TI Stroke: working toward a prioritized world agenda SO INTERNATIONAL JOURNAL OF STROKE LA English DT Editorial Material DE prevention; rehabilitation; stroke; translational; treatment ID VASCULAR COGNITIVE IMPAIRMENT; TISSUE-PLASMINOGEN ACTIVATOR; TRANSIENT ISCHEMIC ATTACK; HEALTHY LIFE-STYLE; PRIMARY PREVENTION; POLICY STATEMENT; CARE; RECOMMENDATIONS; PROGRESS; BRAIN AB Background and Purpose The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Methods Preliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Results Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures. Conclusions To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress. C1 [Hachinski, Vladimir] Univ Western Ontario, London Hlth Sci Ctr, Dept Clin Neurol Sci, London, ON N6A 5A5, Canada. [Donnan, Geoffrey A.] Florey Neurosci Inst, Carlton S Victoria, Australia. [Gorelick, Philip B.] Univ Illinois, Chicago, IL USA. [Hacke, Werner] Univ Heidelberg, Heidelberg, Germany. [Cramer, Steven C.] Univ Calif Irvine, Orange, CA 92668 USA. [Kaste, Markku] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Fisher, Marc] Univ Massachusetts, Sch Med, Worcester, MA USA. [Brainin, Michael] Univ Krems, Univ Donau, Krems, Austria. [Buchan, Alastair M.] Univ Oxford, Oxford, England. [Lo, Eng H.; Furie, Karen L.; Schwamm, Lee H.] Massachusetts Gen Hosp, Charlestown, MA USA. [Skolnick, Brett E.] Novo Nordisk AS, Princeton, NJ USA. [Hankey, Graeme J.] Royal Perth Hosp, Perth, WA, Australia. [Kivipelto, Miia] Karolinska Inst, Stockholm, Sweden. [Morris, John; Goldberg, Mark P.] Washington Univ, Sch Med, St Louis, MO USA. [Rothwell, Peter M.] John Radcliffe Hosp, Oxford OX3 9DU, England. [Sacco, Ralph L.] Univ Miami, AHA, Miami, FL USA. [Smith, Sidney C., Jr.] Univ N Carolina, Ctr Cardiovasc Sci & Med, Chapel Hill, NC USA. World Heart Federat, Geneva, Switzerland. [Wang, Yulun] InTouch Hlth, Goleta, CA USA. [Bryer, Alan] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Bryer, Alan] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Ford, Gary A.] Univ Newcastle, Newcastle Upon Tyne, Tyne & Wear, England. [Iadecola, Costantino] Weill Cornell Med Coll, New York, NY USA. [Martins, Sheila C. O.] Hosp Clin, Porto Alegre, RS, Brazil. [Saver, Jeff] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Skvortsova, Veronika] Russian State Res Stroke Inst, Moscow, Russia. [Bayley, Mark] Toronto Rehabil Inst, Toronto, ON, Canada. [Bednar, Martin M.] Pfizer Inc, Neurosci Res Unit, Groton, CT 06340 USA. [Duncan, Pamela] Duke Univ, Durham, NC USA. [Enney, Lori] GlaxoSmithKline Inc, Durham, NC USA. [Finklestein, Seth] Biotrofix Inc, Waltham, MA USA. [Jones, Theresa A.] Univ Texas Austin, Austin, TX 78712 USA. [Kalra, Lalit] Kings Coll London, London WC2R 2LS, England. [Kleim, Jeff] Univ Florida, Gainesville, FL USA. [Nitkin, Ralph] NICHHD, Natl Ctr Med Rehabil, NIH, Rockville, MD USA. [Teasell, Robert] St Josephs Healthcare London, London, ON, Canada. [Weiller, Cornelius] Univ Freiburg, Freiburg, Germany. [Desai, Bhupat] Pomona Valley Hosp Med Ctr, Pomona, CA USA. [Heiss, Wolf-Dieter] Max Planck Inst Neurol Res, Cologne, Germany. [Saarelma, Osmo] Terveystalo Med Ctr, Helsinki, Finland. [Shinohara, Yukito] Tachikawa Hosp, Tokyo, Japan. [Trivedi, Bhargava] So Illinois Healthcare, Carbondale, IL USA. [Wahlgren, Nils] Karolinska Inst, Stockholm, Sweden. [Wong, Lawrence K.] Chinese Univ Hong Kong, Sha Tin, Hong Kong, Peoples R China. Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Hakim, Antoine] Univ Ottawa, Canadian Stroke Network, Ottawa, ON, Canada. [Norrving, Bo] Univ Lund Hosp, S-22185 Lund, Sweden. [Prudhomme, Stephen] Amer Heart Assoc, Dallas, TX USA. [Bornstein, Natan M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel. Univ Melbourne, Melbourne, Vic, Australia. [Davis, Stephen M.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Goldstein, Larry B.] Duke Univ, Durham, NC USA. [Goldstein, Larry B.] Durham VA Med Ctr, Durham, NC USA. [Leys, Didier] Univ Lille Nord France, Lille, France. [Tuomilehto, Jaakko] Univ Helsinki, Helsinki, Finland. RP Hachinski, V (reprint author), Univ Western Ontario, Univ Hosp, 339 Windermere Rd, London, ON N6A 5A5, Canada. EM Vladimir.Hachinski@lhsc.on.ca RI Jones, Theresa/F-1182-2010; Skolnick, Brett/B-5140-2009; Ford, Gary/A-6353-2012; Buchan, Alastair/B-9095-2009; Hankey, Graeme /H-4968-2014; OI Kaste, Markku/0000-0001-6557-6412; Jones, Theresa/0000-0003-0906-6439; Buchan, Alastair/0000-0002-2918-5200; Hankey, Graeme /0000-0002-6044-7328; Donnan, Geoffrey/0000-0001-6324-3403; Saver, Jeffrey/0000-0001-9141-2251; Norrving, Bo/0000-0002-8024-5096; Schwamm, Lee/0000-0003-0592-9145; Kivipelto, Miia/0000-0003-0992-3875 FU Medical Research Council [G0500495]; NINDS NIH HHS [P01 NS055104, RC2 NS069335] NR 87 TC 17 Z9 18 U1 0 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD AUG PY 2010 VL 5 IS 4 BP 238 EP 256 DI 10.1111/j.1747-4949.2010.00442.x PG 19 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 619RC UT WOS:000279446600002 PM 20636706 ER PT J AU Jura, Y Townsend, M Grodstein, F AF Jura, Y. Townsend, M. Grodstein, F. TI CAFFEINE INTAKE AND RISK OF STRESS, URGENCY, AND MIXED URINARY INCONTINENCE SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Meeting Abstract C1 [Jura, Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Townsend, M.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Grodstein, F.] Brigham & Womens Hosp, 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 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD AUG PY 2010 VL 21 SU 1 MA 165 BP S234 EP S235 PG 2 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 640OV UT WOS:000281061800166 ER PT J AU Weinstein, M Pulliam, S Wakamatsu, M AF Weinstein, M. Pulliam, S. Wakamatsu, M. TI MINIMALLY-INVASIVE SACRAL COLPOPEXY: COMPARISON OF OPERATIVE CHARACTERISTICS OF LAPAROSCOPIC AND ROBOTIC APPROACHES. SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Meeting Abstract C1 [Weinstein, M.; Pulliam, S.; Wakamatsu, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 2 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 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD AUG PY 2010 VL 21 SU 1 MA 256 BP S367 EP S368 PG 2 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 640OV UT WOS:000281061800257 ER PT J AU Wang, DY Ray, A Rodgers, K Ergorul, C Hyman, BT Huang, W Grosskreutz, CL AF Wang, Dan Yi Ray, Arjun Rodgers, Kathryn Ergorul, Ceren Hyman, Bradley T. Huang, Wei Grosskreutz, Cynthia L. TI Global Gene Expression Changes in Rat Retinal Ganglion Cells in Experimental Glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LASER CAPTURE MICRODISSECTION; OPTIC-NERVE TRANSECTION; MICROARRAY ANALYSIS; INTRAOCULAR-PRESSURE; MODEL; ACTIVATION; SURVIVAL; PHOSPHORYLATION; MECHANISMS; NEURONS AB PURPOSE. Intraocular pressure (IOP) is an important risk factor in glaucoma. Gene expression changes were studied in glaucomatous rat retinal ganglion cells (RGCs) to elucidate altered transcriptional pathways. METHODS. RGCs were back-labeled with Fluorogold. Unilateral IOP elevation was produced by injection of hypertonic saline into the episcleral veins. Laser capture microdissection (LCM) was used to capture an equal number of RGCs from normal and glaucomatous retinal sections. RNA was extracted and amplified, labeled, and hybridized to rat genome microarrays, and data analysis was performed. After selected microarray data were confirmed by RT-qPCR and immunohistochemistry, biological pathway analyses were performed. RESULTS. Significant changes were found in the expression of 905 genes, with 330 genes increasing and 575 genes decreasing in glaucomatous RGCs. Multiple cellular pathways were involved. Ingenuity pathway analysis demonstrated significant changes in cardiac beta-adrenergic signaling, interferon signaling, glutamate receptor signaling, cAMP-mediated signaling, chemokine signaling, 14-3-3-mediated signaling, and G-protein-coupled receptor signaling. Gene set enrichment analysis showed that the genes involved in apoptotic pathways were enriched in glaucomatous RGCs. The prosurvival gene Stat3 was upregulated in response to elevated IOP, and immunohistochemistry confirmed that Stat3 and phosphorylated-Stat3 levels were increased in RGCs in experimental glaucoma. In addition, the expression of several prosurvival genes normally expressed in RGCs was decreased. CONCLUSIONS. There are extensive changes in gene expression in glaucomatous RGCs involving multiple molecular pathways, including prosurvival and prodeath genes. The alteration in the balance between prosurvival and prodeath may contribute to RGC death in glaucoma. (Invest Ophthalmol Vis Sci. 2010;51:4084-4095) DOI:10.1167/iovs.09-4864 C1 [Wang, Dan Yi; Ray, Arjun; Rodgers, Kathryn; Ergorul, Ceren; Huang, Wei; Grosskreutz, Cynthia L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Hyman, Bradley T.] Harvard Univ, MassGen Inst Neurodegenerat Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM cynthia_grosskreutz@meei.harvard.edu FU National Eye Institute [R01-EY13399, EY014104]; Cannistraro Fund; Margolis fund FX Supported by the Massachusetts Lions Eye Research Fund, National Eye Institute Grant R01-EY13399, the Cannistraro Fund, the Margolis fund, and National Eye Institute Core Facility Grant EY014104. NR 35 TC 27 Z9 28 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2010 VL 51 IS 8 BP 4084 EP 4095 DI 10.1167/iovs.09-4864 PG 12 WC Ophthalmology SC Ophthalmology GA 629JT UT WOS:000280194100037 PM 20335623 ER PT J AU Fan, BJ Liu, K Wang, DY Tham, CCY Tam, POS Lam, DSC Pang, CP AF Fan, Bao Jian Liu, Ke Wang, Dan Yi Tham, Clement C. Y. Tam, Pancy O. S. Lam, Dennis S. C. Pang, Chi Pui TI Association of Polymorphisms of Tumor Necrosis Factor and Tumor Protein p53 with Primary Open-Angle Glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID NORMAL-TENSION GLAUCOMA; NITRIC-OXIDE SYNTHASE; S-TRANSFERASE M1; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; ALPHA PROMOTER POLYMORPHISMS; CODON 72 POLYMORPHISM; TNF-ALPHA; PSEUDOEXFOLIATION GLAUCOMA; OPA1 POLYMORPHISMS; RISK-FACTOR AB PURPOSE. To evaluate the variants of 10 genes for association with primary open-angle glaucoma (POAG) in a Chinese population. METHODS. A total of 405 unrelated patients with POAG (255 high-tension glaucoma [HTG], 100 normal-tension glaucoma [NTG], and 50 juvenile-onset open-angle glaucoma [JOAG]) and 201 control subjects were recruited. Seventeen variants in 10 genes with reported association with POAG were geno-typed for analysis of allele and haplotype frequencies between cases and control subjects. These genes included CDH1 (cadherin 1, type 1, E-cadherin), CDKN1A (cyclin-dependent kinase inhibitor 1A), CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1), GSTM1 (glutathione S-transferase mu 1), GSTT1 (glutathione S-transferase theta 1), MTHFR (5,10-methylenetetrahydrofolate reductase), NOS3 (nitric oxide synthase 3), OPA1 (optic atrophy 1), TNF (tumor necrosis factor), and TP53 (tumor protein p53). RESULTS. One SNP (-308G>A; rs1800629) in TNF demonstrated a significant association with HTG (P = 0.012). The allele G frequency was higher in HTG patients than in control subjects (94.6% vs. 90.3%; OR = 1.89). One haplotype consisting of rs1799724 and rs1800629 was significantly associated with HTG (P = 0.015, corrected P = 0.045). One SNP (R72P; rs1042522) in TP53 was significantly associated with NTG (P = 0.018). The allele G frequency was higher in NTG patients than in control subjects (56.1% vs. 45.8%; OR = 1.52). The significance of these associations survived the Bonferroni correction (corrected P < 0.024). Other gene variants were not significantly associated with HTG (P > 0.063) or NTG (P > 0.13). None of the studied variants was significantly associated with JOAG (P > 0.17). CONCLUSIONS. The findings suggest that variants in TNF and TP53 are risk factors for POAG, whereas variants in other studied genes are not major risk factors for POAG, at least in the Chinese population. (Invest Ophthalmol Vis Sci. 2010;51:4110-4116) DOI:10.1167/iovs.09-4974 C1 [Fan, Bao Jian; Liu, Ke; Wang, Dan Yi; Tham, Clement C. Y.; Tam, Pancy O. S.; Lam, Dennis S. C.; Pang, Chi Pui] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Kowloon, Hong Kong, Peoples R China. [Fan, Bao Jian; Wang, Dan Yi] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Pang, CP (reprint author), Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, 147K Argyle St, Kowloon, Hong Kong, Peoples R China. EM cppang@cuhk.edu.hk RI Pang, Chi/I-5388-2014; OI Fan, Baojian/0000-0002-6851-2737 FU University Grants Committee, Hong Kong; Research Grant Council, Hong Kong [2140597] FX Supported in part by a block grant from the University Grants Committee, Hong Kong, and by General Research Fund Grant 2140597 from the Research Grant Council, Hong Kong. NR 78 TC 44 Z9 45 U1 1 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2010 VL 51 IS 8 BP 4110 EP 4116 DI 10.1167/iovs.09-4974 PG 7 WC Ophthalmology SC Ophthalmology GA 629JT UT WOS:000280194100040 PM 20357201 ER PT J AU Christen, T Sheikine, Y Rocha, VZ Hurwitz, S Goldfine, AB Di Carli, M Libby, P AF Christen, Thomas Sheikine, Yuri Rocha, Viviane Z. Hurwitz, Shelley Goldfine, Allison B. Di Carli, Marcelo Libby, Peter TI Increased Glucose Uptake in Visceral Versus Subcutaneous Adipose Tissue Revealed by PET Imaging SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE adipose tissue; adipocytes; stromal vascular cells; fluorodeoxyglucose; positron emission tomography; glucose uptake; inflammation ID CARDIOVASCULAR-DISEASE; INSULIN STIMULATION; ABDOMINAL OBESITY; FAT DEPOT; TOMOGRAPHY; ADIPOCYTES; CELLS; BASAL; RISK AB OBJECTIVES The current study tested the hypothesis that glucose utilization differs between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and investigated potential mechanisms for such a finding. BACKGROUND VAT burden correlates better with cardiovascular risk than does SAT burden. Beyond volumetric measurement, glucose uptake in adipose tissue (AT) might reflect metabolic activity and provide pathophysiologic insight and aid risk stratification. METHODS We retrospectively studied tissue-specific glucose uptake in vivo in clinically obtained whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) scans in humans. We also assessed glucose uptake in vitro, using stromal vascular cells isolated from SAT and VAT of diet-induced obese C57BL/6 mice. Quantitative polymerase chain reaction (PCR) evaluated the expression of multiple genes involved in cellular glucose metabolism, including glucose transporters (GLUT-1, -3, and -4) and hexokinases (HK-1 and -2) in SAT and VAT of obese C57BL/6 mice. RESULTS We analyzed whole-body FDG-PET scans from 31 obese and 26 lean patients. VAT exhibited higher FDG uptake compared with SAT (p < 0.0001) independent of age, sex, body mass index, comorbidities, and medications. To investigate mechanisms underlying this observation, we studied glucose uptake in the stromal vascular cell fraction of AT, which is rich in inflammatory cells. Stromal vascular cells from VAT of diet-induced obese C57BL/6 mice exhibited higher glucose uptake than those from SAT (p = 0.01). Evaluation of expression of glucose transporters (GLUT-1, -3, and -4) and hexokinases (HK-1 and -2), revealed increased expression of HK-1 in VAT-derived compared with SAT-derived stromal vascular cells, and also in visceral versus subcutaneous unfractionated AT. CONCLUSIONS In humans in vivo, VAT has increased glucose uptake compared with SAT, as determined noninvasively with FDG PET imaging. Differential stromal metabolic activity may be 1 mechanism underlying differences in metabolic activity of visceral and subcutaneous AT. (J Am Coll Cardiol Img 2010;3:843-51) (C) 2010 by the American College of Cardiology Foundation C1 [Christen, Thomas; Rocha, Viviane Z.; Di Carli, Marcelo; Libby, Peter] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Sheikine, Yuri; Di Carli, Marcelo] Brigham & Womens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [Sheikine, Yuri; Di Carli, Marcelo] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, Dept Med Cardiol, Boston, MA 02115 USA. [Sheikine, Yuri; Di Carli, Marcelo] Brigham & Womens Hosp, Dept Radiol, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Goldfine, Allison B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Libby, P (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,Dept Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM plibby@rics.bwh.harvard.edu FU Donald W. Reynolds Foundation [U01HL080731] FX From the *Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, dagger Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, double dagger Noninvasive Cardiovascular Imaging Program, Departments of Medicine (Cardiology) and Radiology, Brigham and Women's Hospital, Boston, Massachusetts, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and the parallel to Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts. This work was funded in part by the Donald W. Reynolds Foundation, Translational Program of Excellence in Nanotechnology grant U01HL080731. Drs. Christen, Sheikine, and Rocha contributed equally to this study. An alternative spelling of Dr. Sheikine's name is Yury Sheykin. NR 20 TC 35 Z9 36 U1 0 U2 3 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 AUG PY 2010 VL 3 IS 8 BP 843 EP 851 DI 10.1016/j.jcmg.2010.06.004 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 647OE UT WOS:000281627000008 PM 20705265 ER PT J AU Donnelly, P Maurovich-Horvat, P Vorpahl, M Nakano, M Kaple, RK Warger, W Tanaka, A Tearney, G Virmani, R Hoffmann, U AF Donnelly, Patrick Maurovich-Horvat, Pal Vorpahl, Marc Nakano, Masataka Kaple, Ryan K. Warger, William Tanaka, Atsushi Tearney, Guillermo Virmani, Renu Hoffmann, Udo TI Multimodality Imaging Atlas of Coronary Atherosclerosis SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material ID AMERICAN-HEART-ASSOCIATION; VASCULAR-LESIONS; ARTERIOSCLEROSIS; CLASSIFICATION; DEFINITION; COMMITTEE; COUNCIL; PLAQUE C1 [Donnelly, Patrick; Maurovich-Horvat, Pal; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Kaple, Ryan K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Warger, William; Tanaka, Atsushi; Tearney, Guillermo] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Maurovich-Horvat, Pal] Semmelweis Univ, Ctr Heart, Budapest, Hungary. [Vorpahl, Marc; Nakano, Masataka; Virmani, Renu] CV Path Inst Inc, Gaithersburg, MD USA. [Tearney, Guillermo] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Tearney, Guillermo] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 8 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 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD AUG PY 2010 VL 3 IS 8 BP 876 EP 880 DI 10.1016/j.jcmg.2010.06006 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 647OE UT WOS:000281627000013 PM 20705270 ER PT J AU Pride, YB Tung, P Mohanavelu, S Zorkun, C Wiviott, SD Antman, EM Giugliano, R Braunwald, E Gibson, CM AF Pride, Yuri B. Tung, Patricia Mohanavelu, Satishkumar Zorkun, Cafer Wiviott, Stephen D. Antman, Elliott M. Giugliano, Robert Braunwald, Eugene Gibson, C. Michael CA TIMI Study Grp TI Angiographic and Clinical Outcomes Among Patients With Acute Coronary Syndromes Presenting With Isolated Anterior ST-Segment Depression A TRITON TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis In Myocardial Infarction 38) Substudy SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE acute coronary syndrome; ST-segment elevation myocardial infarction; electrocardiography ID ELEVATION; MORTALITY; EMERGENCY; MULTICENTER; REPERFUSION; CLOPIDOGREL; IMPACT; ARTERY AB Objectives This study sought to determine angiographic and clinical outcomes among patients with acute coronary syndrome (ACS) presenting with isolated anterior ST-segment depression on 12-lead electrocardiogram (ECG). Background In patients with ACS, anterior ST-segment depression on 12-lead ECG may represent plaque rupture with: 1) acute thrombotic occlusion with elevation of cardiac biomarkers (+Tn); 2) a patent artery with +Tn; or 3) a patent artery with -Tn. Methods The TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38) enrolled 13,608 ACS patients. Those with isolated anterior (leads V(1) to V(4)) ST-segment depression were analyzed. Angiograms and ECGs were interpreted by local investigators. Results There were 1,198 (8.8%) patients with isolated anterior ST-segment depression. Of those, 314 (26.2%) had an occluded culprit artery (TIMI flow grade 0/1) and +Tn, 641 (53.5%) had a patent culprit artery (TIMI flow grade 2/3) and +Tn, and 243 (20.3%) had TIMI flow grade 2/3 and -Tn. Among patients with an occluded artery, the culprit artery was most often the left circumflex artery (48.4%). The 30-day incidence of the composite of death and MI was significantly higher among patients with an occluded artery (8.6%) than among those with a patent culprit artery and either +Tn (6.3%) or -Tn (2.9%) (3-way p = 0.006). Among patients with an occluded artery, the median time from ECG to percutaneous coronary intervention was 29.4 h (interquartile range 26.1 to 44.1 h). Conclusions Among ACS patients presenting with isolated anterior ST-segment depression, over one-quarter had an occluded culprit artery and elevated cardiac biomarkers. These patients had significantly worse clinical outcomes, and few underwent urgent angiography. (J Am Coll Cardiol Intv 2010;3:806-11) (c) 2010 by the American College of Cardiology Foundation C1 [Gibson, C. Michael] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02115 USA. [Mohanavelu, Satishkumar; Wiviott, Stephen D.; Antman, Elliott M.; Giugliano, Robert; Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Pride, Yuri B.; Tung, Patricia; Zorkun, Cafer] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA USA. RP Gibson, CM (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@perfuse.org FU Daiichi-Sankyo Company, Ltd.; Eli Lilly and Company; Schering-Plough; Sanofi-Aventis; AstraZeneca; ARENA; Novartis; Merck; Bristol-Myers Squibb FX The TRITON TEVII 38 study was supported by a grant from Daiichi-Sankyo Company, Ltd. and Eli Lilly and Company. Dr. Braunwald has received grant support from Eli Lilly and Company and Daiichi-Sankyo, recieves lecture fees from Eli Lilly and Company, and is a member of the Advisory Board of Daiichi-Sankyo. Dr. Wiviott has received research grants from Eli Lilly and Company, Daiichi-Sankyo, Schering-Plough, consulting fees from Sanofi-Aventis, AstraZeneca, and ARENA, and has received lecture fees from Eli Lilly and Company, Daiichi-Sankyo, AstraZeneca, and Novartis. Dr. Giugliano has received lecture fees from Sanofi-Aventis, Merck, and Bristol-Myers Squibb, is a consultant for Merck, HeartScape, Sanofi-Aventis, Daiichi-Sankyo, and Angel Med, and has participated in clinical trials/research support for Daiichi-Sanlcyo and Merck. All other authors report that they have no relationships to disclose. NR 22 TC 24 Z9 24 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD AUG PY 2010 VL 3 IS 8 BP 806 EP 811 DI 10.1016/j.jcin.2010.05.012 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645LI UT WOS:000281458700004 PM 20723851 ER PT J AU Hatano, H Lampiris, H Fransen, S Gupta, S Huang, W Hoh, R Martin, JN Lalezari, J Bangsberg, D Petropoulos, C Deeks, SG AF Hatano, Hiroyu Lampiris, Harry Fransen, Signe Gupta, Soumi Huang, Wei Hoh, Rebecca Martin, Jeffrey N. Lalezari, Jacob Bangsberg, David Petropoulos, Christos Deeks, Steven G. TI Evolution of Integrase Resistance During Failure of Integrase Inhibitor-Based Antiretroviral Therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE integrase inhibitors; drug resistance; virologic failure ID TREATMENT-EXPERIENCED PATIENTS; HIV-1 INFECTION; CONTROLLED-TRIAL; RALTEGRAVIR; EFFICACY; SAFETY; REPLICATION; SUBGROUP AB Background: Although integrase inhibitors are highly effective in the management of drug-resistant HIV, some patients fail to achieve durable viral suppression. The long-term consequences of integrase inhibitor failure have not been well defined. Methods: We identified 29 individuals who exhibited evidence of incomplete viral suppression on a regimen containing an integrase inhibitor (23 raltegravir, 6 elvitegravir). Before initiating the integrase inhibitor-based regimen, the median CD4(+) T-cell count and plasma HIV RNA levels were 62 cells/mm(3) and 4.65 log(10) copies/mL, respectively. Results: At the first failure time-point, the most common integrase resistance pattern for subjects taking raltegravir was wild-type, followed in order of frequency by Q148H/K/R+G140S, N155H, and Y143R/H/C. The most common resistance pattern for subjects taking elvitegravir was E92Q. Long-term failure was associated with continued viral evolution, emergence of high-level phenotypic resistance, and a decrease in replicative capacity. Conclusions: Although wild-type failure during early integrase inhibitor failure is common, most patients eventually develop high-level phenotypic drug resistance. This resistance evolution is gradual and associated with declines in replicative capacity. C1 [Hatano, Hiroyu; Lampiris, Harry; Hoh, Rebecca; Martin, Jeffrey N.; Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lampiris, Harry] San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Fransen, Signe; Gupta, Soumi; Huang, Wei; Petropoulos, Christos] Monogram Biosci, San Francisco, CA USA. [Lalezari, Jacob] Quest Clin Res, San Francisco, CA USA. [Bangsberg, David] Harvard Univ, Sch Med, Boston, MA USA. RP Hatano, H (reprint author), San Francisco Gen Hosp, Bldg 80,Ward 84,995 Potrero Ave, San Francisco, CA 94110 USA. EM hhatano@php.ucsf.edu FU NIAID [K23AI075985, K24 AI069994]; UCSF/Gladstone Center for AIDS Research [P30 AI27763, P30 MH59037]; Center for AIDS Prevention Studies [P30 MH62246]; UCSF Clinical and Translational Science Institute [UL1 RR024131-01]; NIH NIAID [SBIR- R43 AI057074-01]; Merck; Monogram Biosciences; Gilead FX This work was supported by grants from the NIAID (K23AI075985, K24 AI069994), the UCSF/Gladstone Center for AIDS Research (P30 AI27763, P30 MH59037), the Center for AIDS Prevention Studies (P30 MH62246), and the UCSF Clinical and Translational Science Institute (UL1 RR024131-01). The development of the PhenoSense (R) Integrase assay was partially supported by NIH NIAID SBIR- R43 AI057074-01.; Potential conflicts of interest. SG, SF, WH, and CP are employees of Monogram Biosciences. HH has received research support from Merck and Monogram Biosciences. SD has received research support from Merck, Gilead, and Monogram Biosciences. NR 13 TC 38 Z9 39 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2010 VL 54 IS 4 BP 389 EP 393 DI 10.1097/QAI.0b013e3181c42ea4 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 627BR UT WOS:000280013600008 PM 20300008 ER PT J AU Willig, JH Nevin, CR Raper, JL Saag, MS Mugavero, MJ Willig, AL Burkhardt, JH Schumacher, JE Johnson, VA AF Willig, James H. Nevin, Christa R. Raper, James L. Saag, Michael S. Mugavero, Michael J. Willig, Amanda L. Burkhardt, Jeffrey H. Schumacher, Joseph E. Johnson, Victoria A. TI Cost Ramifications of Increased Reporting of Detectable Plasma HIV-1 RNA Levels by the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Version 1.0 Viral Load Test SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID VIRUS TYPE-1 RNA; ANTIRETROVIRAL THERAPY; AMPLICOR; ASSAY; FAILURE; MONITOR C1 [Willig, James H.; Nevin, Christa R.; Raper, James L.; Saag, Michael S.; Mugavero, Michael J.; Johnson, Victoria A.] Birmingham Vet Affairs Med Ctr, Div Infect Dis, Dept Internal Med, Birmingham, AL USA. [Willig, Amanda L.] Birmingham Vet Affairs Med Ctr, Dept Nutr Sci, Birmingham, AL USA. [Burkhardt, Jeffrey H.] Birmingham Vet Affairs Med Ctr, Dept Hlth Serv Adm, Birmingham, AL USA. [Schumacher, Joseph E.] Birmingham Vet Affairs Med Ctr, Dept Med, Div Prevent Med, Birmingham, AL USA. RP Willig, JH (reprint author), Birmingham Vet Affairs Med Ctr, Div Infect Dis, Dept Internal Med, Birmingham, AL USA. OI Willig, Amanda/0000-0001-8802-4311 FU NCI NIH HHS [CA 47888, R25 CA047888]; NIAID NIH HHS [P30 AI027767, R24 AI067039-04, R24 AI067039, 1 R24 AI067039-1, P30-AI27767, P30 AI027767-21A1] NR 12 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2010 VL 54 IS 4 BP 442 EP 444 DI 10.1097/QAI.0b013e3181d01d1d PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 627BR UT WOS:000280013600016 PM 20611035 ER PT J AU Tyer-Viola, LA Duffy, ME AF Tyer-Viola, Lynda A. Duffy, Mary E. TI The Pregnant Women with HIV Attitude Scale: development and initial psychometric evaluation SO JOURNAL OF ADVANCED NURSING LA English DT Article DE HIV; AIDS; instrument development; midwives; obstetric nurses; Pregnant Women with HIV Attitude Scale; psychometric evaluation ID POSITIVE WOMEN; NURSES ATTITUDES; CARE PROVIDERS; MATERNITY CARE; HIV/AIDS; STIGMA; AIDS; KNOWLEDGE; PERCEPTIONS; INFECTION AB P>Title. The Pregnant Women with HIV Attitude Scale: development and initial psychometric evaluation. Aim. This paper is a report of the development and initial psychometric evaluation of the Pregnant Women with HIV Attitude Scale. Background. Previous research has identified that attitudes toward persons with HIV/AIDS have been judgmental and could affect clinical care and outcomes. Stigma towards persons with HIV has persisted as a barrier to nursing care globally. Women are more vulnerable during pregnancy. An instrument to specifically measure obstetric care provider's attitudes toward this population is needed to target identified gaps in providing respectful care. Methods. Existing literature and instruments were analysed and two existing measures, the Attitudes about People with HIV Scale and the Attitudes toward Women with HIV Scale, were combined to create an initial item pool to address attitudes toward HIV-positive pregnant women. The data were collected in 2003 with obstetric nurses attending a national conference in the United States of America (N = 210). Content validity was used for item pool development and principal component analysis and analysis of variance were used to determine construct validity. Reliability was analysed using Cronbach's Alpha. Results. The new measure demonstrated high internal consistency (alpha estimates = 0 center dot 89). Principal component analysis yielded a two-component structure that accounted for 45% of the total variance: Mothering-Choice (alpha estimates = 0 center dot 89) and Sympathy-Rights (alpha estimates = 0 center dot 72). Conclusion. These data provided initial evidence of the psychometric properties of the Pregnant Women with HIV Attitude Scale. Further analysis is required of the validity of the constructs of this scale and its reliability with various obstetric care providers. C1 [Tyer-Viola, Lynda A.] Massachusetts Gen Hosp Inst Hlth Profess, Boston, MA USA. [Duffy, Mary E.] Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Tyer-Viola, LA (reprint author), Massachusetts Gen Hosp Inst Hlth Profess, Boston, MA USA. EM ltyerviola@partners.org FU Alpha Chi Chapter of Sigma Theta Tau; Yvonne L. Munn Center for Nursing Research, Massachusetts General Hospital FX Funding for this study was from The Alpha Chi Chapter of Sigma Theta Tau and The Yvonne L. Munn Center for Nursing Research, Massachusetts General Hospital. NR 71 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-2402 J9 J ADV NURS JI J. Adv. Nurs. PD AUG PY 2010 VL 66 IS 8 BP 1852 EP 1863 DI 10.1111/j.1365-2648.2009.05234.x PG 12 WC Nursing SC Nursing GA 619RG UT WOS:000279447100020 PM 20557397 ER PT J AU Vassallo, MF Camargo, CA AF Vassallo, Milo F. Camargo, Carlos A., Jr. TI Potential mechanisms for the hypothesized link between sunshine, vitamin D, and food allergy in children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Food allergy; vitamin D; vitamin D deficiency; mucosal immunity; epithelial barrier; microbial ecology; infections; sensitization; atopy ID REGULATORY T-CELLS; BODY-MASS INDEX; D DEFICIENCY; ATOPIC-DERMATITIS; 1,25-DIHYDROXYVITAMIN D-3; UNITED-STATES; ORAL TOLERANCE; IMMUNE-SYSTEM; US CHILDREN; D-RECEPTOR AB Epidemiologic data suggest that the incidence of food allergy (FA) is increasing among children, yet a satisfactory model of its pathogenesis remains elusive. FA is the consequence of maladaptive immune responses to common and otherwise innocuous food antigens. Concurrent with the increase in FA is an epidemic of vitamin D deficiency (VDD) caused by several factors, especially decreased sunlight/UVB exposure. There is growing appreciation of the importance of the pleiotropic hormone vitamin D in the development of tolerance, immune system defenses, and epithelial barrier integrity. We propose a "multiplehit'' model in which VDD in a developmentally critical period increases susceptibility to colonization with abnormal intestinal microbial flora and gastrointestinal infections, contributing to abnormal intestinal barrier permeability and excess and inappropriate exposure of the immune system to dietary allergens. A compounding effect (and additional "hit'') of VDD is the promotion of a pro-sensitization immune imbalance that might compromise immunologic tolerance and contribute to FA. We propose that early correction of VDD might promote mucosal immunity, healthy microbial ecology, and allergen tolerance and thereby blunt the FA epidemic in children. (J Allergy Clin Immunol 2010;126:217-22.) C1 [Vassallo, Milo F.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Dept Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU National Institutes of Health (Bethesda, Md) [T32 AI-060548]; Massachusetts General Hospital Center for D-receptor Activation Research (Boston, Mass); Food Allergy and Anaphylaxis Network (Fairfax, Va) FX M. F. V. was supported by T32 AI-060548 from the National Institutes of Health (Bethesda, Md). C. A. C. was supported, in part, by the Massachusetts General Hospital Center for D-receptor Activation Research (Boston, Mass) and the Food Allergy and Anaphylaxis Network (Fairfax, Va). NR 67 TC 75 Z9 77 U1 3 U2 14 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2010 VL 126 IS 2 BP 217 EP 222 DI 10.1016/j.jaci.2010.06.011 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 642IL UT WOS:000281203800004 PM 20624647 ER PT J AU Lange, NE Rifas-Shiman, SL Camargo, CA Gold, DR Gillman, MW Litonjua, AA AF Lange, Nancy E. Rifas-Shiman, Sheryl L. Camargo, Carlos A., Jr. Gold, Diane R. Gillman, Matthew W. Litonjua, Augusto A. TI Maternal dietary pattern during pregnancy is not associated with recurrent wheeze in children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; dietary pattern; Mediterranean diet; healthy diet; principal components; childhood wheeze; pregnancy ID MAJOR CHRONIC DISEASE; OBSTRUCTIVE PULMONARY-DISEASE; GUIDELINES-FOR-AMERICANS; MEDITERRANEAN DIET; VITAMIN-D; 5-YEAR-OLD CHILDREN; ANTIOXIDANT INTAKE; CHILDHOOD ASTHMA; FOOD-CONSUMPTION; RISK AB Background: The rise in asthma prevalence over the last few decades may be a result of changes in prenatal or early-life environment, including maternal diet during pregnancy. Previous studies have found associations between individual foods or nutrients consumed during pregnancy and asthma or wheeze in children, but these may be confounded by overall dietary pattern. Objective: To determine whether overall maternal dietary pattern during pregnancy is associated with recurrent wheeze in children. Methods: A total of 1376 mother-infant pairs from Project Viva, a longitudinal prebirth cohort, who had responses for food frequency questionnaires in the first and second trimester and outcome data at 3 years of age were included. Multivariable logistic regression was used to look at associations between dietary pattern and the primary outcome of recurrent wheeze at 3 years. Overall dietary pattern was examined by using Mediterranean diet score, Alternate Healthy Eating Index modified for pregnancy (AHEI-P), and principal components analysis to look at Western and Prudent diets. Results: None of these dietary patterns was associated with the primary outcome of recurrent wheeze in children in either the crude or the multivariable model (multivariable model, odds ratio per 1-point increase in Mediterranean diet, 0.98 [95% CI, 0.89-1.08]; AHEI-P, 1.07 [0.87-1.30]; Prudent, 1.02 [0.83-1.26]; Western, 0.98 [0.81-1.19]). Conclusion: Overall dietary pattern during pregnancy is not associated with recurrent wheeze in this cohort. Maternal intake of individual nutrients may be more important determinants of offspring wheeze-associated illness than is dietary pattern. (J Allergy Clin Immunol 2010;126:250-5.) C1 [Lange, Nancy E.; Camargo, Carlos A., Jr.; Gold, Diane R.; Litonjua, Augusto A.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Lange, Nancy E.; Gold, Diane R.; Litonjua, Augusto A.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Lange, Nancy E.; Gold, Diane R.; Litonjua, Augusto A.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Rifas-Shiman, Sheryl L.; Gillman, Matthew W.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Gillman, Matthew W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Lange, NE (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM nlange@partners.org OI Litonjua, Augusto/0000-0003-0422-5875 FU NIH [HL61907, HL64925, HD34568, AI35786, HL68041, HL007427]; AstraZeneca; Dey; GlaxoSmithKline; Merck FX Supported by NIH HL61907, HL64925, HD34568, AI35786, HL68041, and HL007427.; C. A. Camargo Jr is a consultant and speaker for AstraZeneca; is on the advisory board for Dey; is a consultant, is a speaker, and is on the advisory board for GlaxoSmithKline; is a speaker of Merck; is a consultant and is on the advisory board for Novartis; and has received research support from the National Institutes of Health, AstraZeneca, Dey, GlaxoSmithKline, and Merck. D. R. Gold has received research support from the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest. NR 54 TC 20 Z9 22 U1 2 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2010 VL 126 IS 2 BP 250 EP U13 DI 10.1016/j.jaci.2010.05.009 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 642IL UT WOS:000281203800008 PM 20584543 ER PT J AU Rudders, SA Banerji, A Vassallo, MF Clark, S Camargo, CA AF Rudders, Susan A. Banerji, Aleena Vassallo, Milo F. Clark, Sunday Camargo, Carlos A., Jr. TI Trends in pediatric emergency department visits for food-induced anaphylaxis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID ALLERGY; PREVALENCE C1 [Rudders, Susan A.] Childrens Hosp, Div Allergy & Immunol, Boston, MA 02115 USA. [Rudders, Susan A.; Vassallo, Milo F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Banerji, Aleena; Vassallo, Milo F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Clark, Sunday] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Rudders, SA (reprint author), Childrens Hosp, Div Allergy & Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM ccamargo@partners.org FU NIAID NIH HHS [T32-AI-007512] NR 9 TC 48 Z9 50 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2010 VL 126 IS 2 BP 385 EP 388 DI 10.1016/j.jaci.2010.05.018 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 642IL UT WOS:000281203800026 PM 20621344 ER PT J AU Kunisawa, T Nagashima, M Suzuki, A Takahata, O Iwasaki, H AF Kunisawa, Takayuki Nagashima, Michio Suzuki, Akihiro Takahata, Osamu Iwasaki, Hiroshi TI The range of values of "variable alpha" when predicting plasma concentrations and/or effect site concentrations of remifentanil is huge SO JOURNAL OF ANESTHESIA LA English DT Letter C1 [Kunisawa, Takayuki; Suzuki, Akihiro; Takahata, Osamu; Iwasaki, Hiroshi] Asahikawa Med Coll, Dept Anesthesiol & Crit Care Med, Asahikawa, Hokkaido 0788510, Japan. [Kunisawa, Takayuki] Asahikawa Med Coll Hosp, Surg Operat Dept, Asahikawa, Hokkaido, Japan. [Nagashima, Michio] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Nagashima, Michio] Harvard Univ, Sch Med, Boston, MA USA. RP Kunisawa, T (reprint author), Asahikawa Med Coll, Dept Anesthesiol & Crit Care Med, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido 0788510, Japan. EM taka.kunisawa@nifty.ne.jp OI Nagashima, Michio/0000-0001-7416-5367 NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0913-8668 J9 J ANESTH JI J. Anesth. PD AUG PY 2010 VL 24 IS 4 BP 656 EP 657 DI 10.1007/s00540-010-0961-y PG 2 WC Anesthesiology SC Anesthesiology GA 635IG UT WOS:000280648200031 PM 20505958 ER PT J AU Crompton, JA North, DS Yoon, M Steenbergen, JN Lamp, KC Forrest, GN AF Crompton, Jason A. North, Donald S. Yoon, MinJung Steenbergen, Judith N. Lamp, Kenneth C. Forrest, Graeme N. TI Outcomes with daptomycin in the treatment of Staphylococcus aureus infections with a range of vancomycin MICs SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE lipopeptides; S; aureus; CORE ID MINIMUM INHIBITORY CONCENTRATION; BACTERICIDAL ACTIVITY; PROSPECTIVE MULTICENTER; CLINICAL-OUTCOMES; RISK-FACTORS; BACTEREMIA; SUSCEPTIBILITY; ENDOCARDITIS; RESISTANCE; EFFICACY AB Recent recommendations by the Infectious Diseases Society of America for the treatment of Staphylococcus aureus suggest the use of alternative agents when vancomycin MIC values are >= 2 mg/L. This study examines the outcome of patients treated with daptomycin for S. aureus infections with documented vancomycin MICs. All patients with skin, bacteraemia and endocarditis infections due to S. aureus with vancomycin MIC values in CORE 2005-08, a retrospective, multicentre, observational registry, were studied. The outcome (cure, improved, failure or non-evaluable) was the investigator assessment at the end of daptomycin therapy. Success was defined as cure or improved. Five hundred and forty-seven clinically evaluable patients were identified with discrete vancomycin MIC values [MIC < 2 mg/L: 451 (82%); MIC >= 2 mg/L: 96 (18%)]. The vancomycin MIC groups were well matched for patient characteristics, types of infections, first-line daptomycin use (19%) and prior vancomycin use (58%). Clinical success was reported in 94% of patients. No differences were detected in the daptomycin success rate by the vancomycin MIC group overall or by the infection type. A multivariate logistic regression also failed to identify vancomycin MIC as a predictor of daptomycin failure. Adverse event (AE) rates were not different when analysed by MIC group; both groups had similar to 17% of patients with one AE. In this diverse population, daptomycin was associated with similar outcomes for patients, regardless of whether the vancomycin MIC was categorized as < 2 or >= 2 mg/L. Further studies are warranted. C1 [Crompton, Jason A.; North, Donald S.; Yoon, MinJung; Steenbergen, Judith N.; Lamp, Kenneth C.] Cubist Pharmaceut, Lexington, MA 02421 USA. [Forrest, Graeme N.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Lamp, KC (reprint author), Cubist Pharmaceut, 65 Hayden Ave, Lexington, MA 02421 USA. EM kenneth.lamp@cubist.com FU Cubist Pharmaceuticals, Inc. FX This work was supported by Cubist Pharmaceuticals, Inc. The decision to submit this analysis for publication was made by Cubist Pharmaceuticals and the authors. No financial support or honorarium was given to the non-Cubist Pharmaceuticals author for the development of this manuscript. The Cubist Pharmaceuticals authors were not awarded any additional support outside of their salary for their participation in this study. NR 33 TC 16 Z9 18 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD AUG PY 2010 VL 65 IS 8 BP 1784 EP 1791 DI 10.1093/jac/dkq200 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 627DD UT WOS:000280018400037 PM 20554570 ER PT J AU Neal-Barnett, A Flessner, C Franklin, ME Woods, DW Keuthen, NJ Stein, DJ AF Neal-Barnett, Angela Flessner, Christopher Franklin, Martin E. Woods, Douglas W. Keuthen, Nancy J. Stein, Dan J. TI Ethnic differences in trichotillomania: Phenomenology, interference, impairment, and treatment efficacy SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Minorities; Trichotillomania; Internet study ID AFRICAN-AMERICAN WOMEN; MGH HAIRPULLING SCALE; ANXIETY STRESS SCALES; PSYCHOMETRIC PROPERTIES; ISSUES; COMMUNITY; DISORDER; THERAPY; SAMPLES; IMPACT AB In this Internet study, we explore differences among minority and Caucasian participants in the phenomenology of, interference and impairment related to, and perceived efficacy of treatments for trichotillomania (TTM) symptoms. A demographic difference was found for number of children only. Results indicate that the minority sample was less likely to report pulling from their eyebrows and eyelashes than the Caucasian sample. Minorities were less likely to report increased tension before a pulling episode. Minorities reported high levels of TTM interference with home management but Caucasians reported higher TTM interference with their academic life. Caucasians with TTM reported higher daily stress than their minority counterparts. Although minorities were less likely to utilize treatment, no significant differences were found for treatment improvement. This Internet study sheds important light on differences in TIN symptoms among minorities and Caucasians. The lack of economic and education differences between groups is a strength of this research. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Neal-Barnett, Angela] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Flessner, Christopher] Brown Univ, Providence, RI 02912 USA. [Franklin, Martin E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Woods, Douglas W.] Univ Wisconsin Milwaukee, Milwaukee, WI USA. [Keuthen, Nancy J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Stein, Dan J.] Univ Cape Town, ZA-7700 Rondebosch, South Africa. RP Neal-Barnett, A (reprint author), Kent State Univ, Dept Psychol, Kent, OH 44242 USA. EM aneal@kent.edu RI Citations, TLC SAB/C-4006-2011; Flessner, Christopher/K-1483-2015; Stein, Dan/A-1752-2008 OI Stein, Dan/0000-0001-7218-7810 NR 36 TC 5 Z9 5 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD AUG PY 2010 VL 24 IS 6 BP 553 EP 558 DI 10.1016/j.janxdis.2010.03.014 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 607CU UT WOS:000278476900002 PM 20413254 ER PT J AU Chen, NC Gill, TJ Martin, SD AF Chen, Neal C. Gill, Thomas J. Martin, Scott D. TI Quantitative Anatomy of Medial Femoral Perforators of the Distal Thigh SO JOURNAL OF ARTHROPLASTY LA English DT Article DE knee anatomy; vastus medialis; total knee arthroplasty; mini-incision; perforator ID TOTAL KNEE ARTHROPLASTY; SUBVASTUS APPROACH; MIDVASTUS APPROACH; MUSCLE AB The purpose of the study was to quantitatively examine the anatomical organization of medial femoral perforators. Mini-incision approaches to total knee arthroplasty are being used more often; however, no studies have examined the quantitative anatomy of perforating vessels into the distal intermuscular septum. Fourteen embalmed cadaveric knees were dissected to identify where vascular perforators pierced the medial intermuscular septum. Quantitative measurements were made from the perforators to the medial epicondyle of the femur. The mean measurements from the medial epicondyle to each of the vascular perforators were 7.1, 10.5, and 13.5 cm. The closest perforator to the medial epicondyle was found at a distance of 5.5 cm. During mini-incision approaches to the knee, vascular perforators are at potential risk of injury when dissection proceeds 5 cm proximal to the medial epicondyle. C1 [Chen, Neal C.] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48106 USA. [Gill, Thomas J.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. [Martin, Scott D.] Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA. RP Chen, NC (reprint author), Univ Michigan, Dept Orthopaed Surg, 24 Frank Lloyd Wright Dr, Ann Arbor, MI 48106 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD AUG PY 2010 VL 25 IS 5 BP 803 EP 806 DI 10.1016/j.arth.2009.05.031 PG 4 WC Orthopedics SC Orthopedics GA 639ZE UT WOS:000281015200021 PM 19628367 ER PT J AU Menconi, F Huber, A Osman, R Concepcion, E Jacobson, EM Stefan, M David, CS Tomer, Y AF Menconi, Francesca Huber, Amanda Osman, Roman Concepcion, Erlinda Jacobson, Eric M. Stefan, Mihaela David, Chela S. Tomer, Yaron TI Tg.2098 is a major human thyroglobulin T-cell epitope SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Thyroglobulin; HLA; Gene; Thyroiditis ID AUTOIMMUNE THYROID-DISEASE; MHC CLASS-II; UNIQUE TETRANUCLEOTIDE SEQUENCES; MOLECULAR-DYNAMICS SIMULATIONS; GENETIC SUSCEPTIBILITY; HASHIMOTO THYROIDITIS; DNA OLIGONUCLEOTIDES; RHEUMATOID-ARTHRITIS; GRAVES-DISEASE; RAS-RAF AB An HLA-DR variant containing Arginine at position 74 of the DR beta 1 chain confers a strong genetic susceptibility to autoimmune thyroid diseases (AITD), Graves' disease (GD) and Hashimoto's thyroiditis (HT), while Glutamine at position DR beta 1-74 is protective. We hypothesized that the DR beta 1-Arg74 variant is able to present pathogenic thyroglobulin (Tg) peptides to T-cells more efficiently, thereby triggering thyroid autoimmunity. Indeed, we have previously identified 4 human Tg (hTg) peptides that bind specifically to DR beta 1-Arg74 with much weaker binding to the protective variant DR beta 1-Gln74. The aim of our study was to examine in vivo whether an hTg peptide that binds strongly and specifically to DR beta 1-Arg74 is capable of stimulating T-cells during the induction of thyroiditis in a "humanized" mouse expressing human DR3, and in patients positive for Tg antibodies. Sequencing of exon 2 of the DR transgene in the DR3 mice, null for endogenous MHC II molecules, confirmed that they expressed the disease-associated DR beta 1-Arg74 variant, thus making them an ideal in vivo model to test the presentation of hTg peptides by DR beta 1-Arg74 HLA-DR. Induction of EAT in the DR3 mice lead to T-cell stimulation and proliferation to Tg.2098, a strong and specific DR beta 1-Arg74 binder, while a non-binding control peptide. Tg.2766 did not induce this response. Moreover, Tg.2098 stimulated T-cells from 4 individuals who were positive for thyroglobulin antibodies, demonstrating that Tg.2098 is an immunogenic peptide capable of being presented in vivo and activating T-cells in EAT and AITD. Energetic analysis of the complex formed by Tg.2098 and DR beta-Arg74 has shown that the origin of the affinity was determined by residues 1, 7 and 9 in the peptide, while the selectivity of the peptide for the MHC was determined by the Asp in position 4. The disease-protective substitution R74Q leads to reduction in affinity due to changes in local interaction with D4 as well as non-local interaction with other residues. The electrostatic potential on the surface of the DR beta-Arg74 Tg.2098 complex has a unique signature which may be recognized by T-cell receptors leading to autoimmune thyroiditis. Taken together these findings suggest that Tg.2098, a strong and specific binder to the disease-associated HLA-DR beta-Arg74, is a major human T-cell epitope and participant in the pathoetiology of AITD. Published by Elsevier Ltd. C1 [Menconi, Francesca; Huber, Amanda; Concepcion, Erlinda; Stefan, Mihaela; Tomer, Yaron] Mt Sinai Med Ctr, Dept Med, Div Endocrinol, New York, NY 10029 USA. [Osman, Roman] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY USA. [Jacobson, Eric M.] Univ Cincinnati, Dept Canc & Cell Biol, Cincinnati, OH USA. [David, Chela S.] Mayo Clin, Coll Med, Dept Immunol, Rochester, MN USA. [Tomer, Yaron] James J Peters VA Med Ctr, Bronx, NY USA. RP Tomer, Y (reprint author), Mt Sinai Med Ctr, Dept Med, Div Endocrinol, Box 1118,1 Gustave L Levy Pl, New York, NY 10029 USA. EM Yaron.Tomer@mssm.edu FU NIDDK [DK61659, DK067555, DK073681]; American Thyroid Association FX This work was supported in part by grants DK61659, DK067555, & DK073681 from NIDDK (to YT), and by a grant from the American Thyroid Association (to EMJ). NR 37 TC 10 Z9 11 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD AUG PY 2010 VL 35 IS 1 BP 45 EP 51 DI 10.1016/j.jaut.2010.01.004 PG 7 WC Immunology SC Immunology GA 616HV UT WOS:000279200700006 PM 20303712 ER PT J AU Elo, LL Mykkanen, J Nikula, T Jarvenpaa, H Simell, S Aittokallio, T Hyoty, H Ilonen, J Veijola, R Simell, T Knip, M Simell, O Lahesmaa, R AF Elo, Laura L. Mykkanen, Juha Nikula, Tuomas Jarvenpaa, Henna Simell, Satu Aittokallio, Tero Hyoty, Heikki Ilonen, Jorma Veijola, Riitta Simell, Tuula Knip, Mikael Simell, Olli Lahesmaa, Riitta TI Early suppression of immune response pathways characterizes children with prediabetes in genome-wide gene expression profiling SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Type 1 diabetes; Prediabetes; Autoantibodies; Longitudinal data; Differential gene expression; Molecular networks; Pathway analysis ID LYMPHOID TYROSINE PHOSPHATASE; COMPLEX CLASS-I; DEPENDENT DIABETES-MELLITUS; T-CELL ANERGY; PERIPHERAL-BLOOD; HUMAN THYMUS; B-CELLS; TYPE-1; ANTIGEN; VARIANT AB Type 1 diabetes (T1D) is caused by autoimmune destruction of insulin-producing pancreatic p cells in the islets of Langerhans. Although defects in various T cell subsets have been linked to the disease pathogenesis, mechanisms initiating or enhancing the autoimmunity in prediabetes remain poorly understood. To unravel genes and molecular pathways affected by the diabetes-associated autoimmunity, we investigated transcriptomic profiles of prospective whole-blood samples from children who have developed T1D-associated autoantibodies and eventually clinical T1D. Gene-level investigation of the data showed systematic differential expression of 520 probesets. A network-based analysis revealed then a highly significant down-regulated network of genes involved in antigen presentation as well as T-cell receptor and insulin signaling. Finally, detection of dynamic changes in the affected pathways at the early or late phases of autoimmunity showed down-regulation of several novel T1D-associated pathways as well as known key components of immune response. The longitudinal genome-wide data generated in the present study allows the detection of dynamic changes relevant to the disease that may be completely missed in conventional cross-sectional studies or in genome-wide association studies. Taken together, our analysis showed systemic high-level repression of immune response pathways associated with T1D autoimmunity. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Elo, Laura L.; Mykkanen, Juha; Nikula, Tuomas; Jarvenpaa, Henna; Aittokallio, Tero; Lahesmaa, Riitta] Univ Turku, Turku Ctr Biotechnol, FI-20521 Turku, Finland. [Elo, Laura L.; Mykkanen, Juha; Nikula, Tuomas; Jarvenpaa, Henna; Aittokallio, Tero; Lahesmaa, Riitta] Abo Akad Univ, FI-20521 Turku, Finland. [Elo, Laura L.; Aittokallio, Tero] Univ Turku, Dept Math, FI-20014 Turku, Finland. [Simell, Satu; Simell, Tuula; Simell, Olli] Univ Turku, Dept Pediat, FI-20014 Turku, Finland. [Ilonen, Jorma] Univ Turku, Immunogenet Lab, FI-20014 Turku, Finland. [Hyoty, Heikki] Univ Tampere, Dept Virol, FI-33014 Tampere, Finland. [Hyoty, Heikki] Tampere Univ Hosp, Ctr Lab Med, FI-33520 Tampere, Finland. [Ilonen, Jorma] Univ Kuopio, Dept Clin Microbiol, FI-70211 Kuopio, Finland. [Veijola, Riitta] Univ Oulu, Dept Pediat, FI-90014 Oulu, Finland. [Knip, Mikael] Univ Helsinki, Hosp Children & Adolescents, FI-00014 Helsinki, Finland. [Knip, Mikael] Univ Helsinki, Folkhalsan Res Ctr, FI-00014 Helsinki, Finland. [Knip, Mikael] Tampere Univ Hosp, Dept Pediat, FI-33521 Tampere, Finland. [Lahesmaa, Riitta] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. RP Lahesmaa, R (reprint author), Univ Turku, Turku Ctr Biotechnol, FI-20521 Turku, Finland. EM laura.elo@utu.fi; juha.mykkanen@utu.fi; toumas.nikula@perkinelmer.fi; henna.jarvenpaa@btk.fi; satu.simell@tyks.fi; tero.aittokallio@utu.fi; heikki.hyoty@uta.fi; jorma.ilonen@utu.fi; riitta.veijola@oulu.fi; tuula.simell@utu.fi; mikael.knip@helsinki.fi; olli.simell@utu.fi; riitta.lahesmaa@btk.fi RI Aittokallio, Tero/B-6583-2009; Mykkanen, Juha/Q-1663-2015; OI Aittokallio, Tero/0000-0002-0886-9769; Mykkanen, Juha/0000-0001-9898-2660; Elo, Laura/0000-0001-5648-4532 FU Juvenile Diabetes Research Foundation (JDRF); Academy of Finland; Turku University; Finnish Funding Agency for Technology and Innovation (Tekes); Sigrid Juselius Foundation; DIPP FX We thank all the staff of the DIPP team for their expert help and contribution. DIPP families are thanked for their support. We are grateful for Katja Waenerberg and the Finnish DNA Microarray Centre at Turku Centre for Biotechnology for excellent technical assistance. This study was financially supported by the Juvenile Diabetes Research Foundation (JDRF), the Academy of Finland, the Turku University Hospital Research Fund, the Finnish Funding Agency for Technology and Innovation (Tekes), and the Sigrid Juselius Foundation. NR 56 TC 20 Z9 20 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD AUG PY 2010 VL 35 IS 1 BP 70 EP 76 DI 10.1016/j.jaut.2010.03.001 PG 7 WC Immunology SC Immunology GA 616HV UT WOS:000279200700009 PM 20356713 ER PT J AU Hoover, SE Xu, WH Xiao, WZ Burkholder, WF AF Hoover, Sharon E. Xu, Weihong Xiao, Wenzhong Burkholder, William F. TI Changes in DnaA-Dependent Gene Expression Contribute to the Transcriptional and Developmental Response of Bacillus subtilis to Manganese Limitation in Luria-Bertani Medium SO JOURNAL OF BACTERIOLOGY LA English DT Article ID REPLICATION INITIATION; PEROXIDE STRESS; DEINOCOCCUS-RADIODURANS; HYDROGEN-PEROXIDE; SPORE FORMATION; PROTEIN DNAA; METAL-IONS; CELL-CYCLE; SPORULATION; BACTERIA AB The SOS response to DNA damage in bacteria is a well-known component of the complex transcriptional responses to genotoxic environmental stresses such as exposure to reactive oxygen species, alkylating agents, and many of the antibiotics targeting DNA replication. However, bacteria such as Bacillus subtilis also respond to conditions that perturb DNA replication via a transcriptional response mediated by the replication initiation protein DnaA. In addition to regulating the initiation of DNA replication, DnaA directly regulates the transcription of specific genes. Conditions that perturb DNA replication can trigger the accumulation of active DnaA, activating or repressing the transcription of genes in the DnaA regulon. We report here that simply growing B. subtilis in LB medium altered DnaA-dependent gene expression in a manner consistent with the accumulation of active DnaA and that this was part of a general transcriptional response to manganese limitation. The SOS response to DNA damage was not induced under these conditions. One of the genes positively regulated by DnaA in Bacillus subtilis encodes a protein that inhibits the initiation of sporulation, Sda. Sda expression was induced as cells entered stationary phase in LB medium but not in LB medium supplemented with manganese, and the induction of Sda inhibited sporulation-specific gene expression and the onset of spore morphogenesis. In the absence of Sda, manganese-limited cells initiated spore development but failed to form mature spores. These data highlight that DnaA-dependent gene expression may influence the response of bacteria to a range of environmental conditions, including conditions that are not obviously associated with genotoxic stress. C1 [Hoover, Sharon E.; Burkholder, William F.] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Xu, Weihong; Xiao, Wenzhong] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. [Xiao, Wenzhong] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Burkholder, WF (reprint author), Stanford Univ, Dept Biol, 371 Serra Mall, Stanford, CA 94305 USA. EM burkholder@stanford.edu OI xiao, wenzhong/0000-0003-4944-6380 FU NIH [5T32GM007276]; National Science Foundation [ID 0744872] FX S. E. H. was supported by an NIH predoctoral training grant (5T32GM007276). This work was supported by National Science Foundation award ID 0744872. NR 61 TC 16 Z9 16 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2010 VL 192 IS 15 BP 3915 EP 3924 DI 10.1128/JB.00210-10 PG 10 WC Microbiology SC Microbiology GA 623XZ UT WOS:000279782000008 PM 20511500 ER PT J AU Bensing, BA Sullam, PM AF Bensing, Barbara A. Sullam, Paul M. TI Transport of Preproteins by the Accessory Sec System Requires a Specific Domain Adjacent to the Signal Peptide SO JOURNAL OF BACTERIOLOGY LA English DT Article ID STREPTOCOCCUS-GORDONII DL1; BINDING PROTEIN-GSPB; SECONDARY STRUCTURE PREDICTION; SURFACE GLYCOPROTEINS GSPB; SERINE-RICH ADHESIN; SIALIC-ACID; ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; TRANSLOCATION CHANNEL; SEQUENCE RECOGNITION AB The accessory Sec (SecA2/Y2) systems of streptococci and staphylococci are dedicated to the transport of large serine-rich repeat (SRR) glycoproteins to the bacterial cell surface. The means by which the glycosylated preproteins are selectively recognized by the accessory Sec system have not been fully characterized. In Streptococcus gordonii, the SRR glycoprotein GspB has a 90-residue amino-terminal signal sequence that is essential for transport by SecA2/Y2 but is not sufficient to mediate the transport of heterologous proteins by this specialized transporter. We now report that a preprotein must remain at least partially unfolded prior to transport by the accessory Sec system. In addition, a region of approximately 20 residues from the amino-terminal end of mature GspB (the accessory Sec transport or AST domain) is essential for SecA2/Y2-dependent transport. The replacement of several AST domain residues with glycine strongly interferes with export, which suggests that a helical conformation may be important. Analysis of GspB variants with alterations in the AST domain, in combination with the results with a SecY2 variant, indicates that the AST domain is essential both for targeting to the SecA2/Y2 translocase and for initiating translocation through the SecY2 channel. The combined results suggest a unique mechanism that ensures the transport of a single substrate by the SecA2/Y2 system. C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Sullam, PM (reprint author), Vet Affairs Med Ctr, Div Infect Dis, 111W,4150 Clement St, San Francisco, CA 94121 USA. EM paul.sullam@ucsf.edu FU Department of Veterans Affairs; National Institutes of Health [RO1AI41513, RO1AI057433] FX This work was supported by the Department of Veterans Affairs and the VA Merit Review program and by grants RO1AI41513 and RO1AI057433 from the National Institutes of Health. NR 54 TC 16 Z9 16 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2010 VL 192 IS 16 BP 4223 EP 4232 DI 10.1128/JB.00373-10 PG 10 WC Microbiology SC Microbiology GA 632FL UT WOS:000280406300016 PM 20562303 ER PT J AU Sevick, MA Stone, RA Zickmund, S Wang, YY Korytkowski, M Burke, LE AF Sevick, Mary Ann Stone, Roslyn A. Zickmund, Susan Wang, Yuanyuan Korytkowski, Mary Burke, Lora E. TI Factors associated with probability of personal digital assistant-based dietary self-monitoring in those with type 2 diabetes SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Handheld computer; Randomized clinical trial; Behavioral research; Compliance ID WEIGHT-LOSS PROGRAM; BEHAVIOR-CHANGE; PAPER DIARIES; HEALTH; INTERVENTION; DIVIDE; TECHNOLOGY; COMPUTERS; ADHERENCE; INTERNET AB Knowledge of factors associated with the use of technology could inform the design of technology-based behavioral interventions. This study examined modifiable and nonmodifiable factors associated with technology-based self-monitoring. 123 participants with type 2 diabetes self-monitored diet using a personal digital assistant in a 6-month behavioral intervention. Multinomial logistic regression was used to examine probability of nonadherent and suboptimally adherent behavior relative to adherent behavior. Sociodemographic characteristics were not associated with probability of self-monitoring. Probability of adherence generally was greater in the weeks preceding no group session, and lower in the weeks following no group session or following skipped sessions. Non-modifiable factors suggested by the literature to be associated with poorer access to technology (lower income, older age, minority race, and lower education) were not associated with probability of self-monitoring in this population. C1 [Sevick, Mary Ann; Zickmund, Susan; Korytkowski, Mary] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Sevick, Mary Ann; Stone, Roslyn A.; Zickmund, Susan] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Sevick, Mary Ann; Stone, Roslyn A.; Wang, Yuanyuan; Burke, Lora E.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Burke, Lora E.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. RP Sevick, MA (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. EM sevick@pitt.edu FU NCRR NIH HHS [M01-RR000056, UL1-RR024153]; NIDDK NIH HHS [DK-046204]; NINR NIH HHS [NR-R01008792] NR 54 TC 10 Z9 11 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD AUG PY 2010 VL 33 IS 4 BP 315 EP 325 DI 10.1007/s10865-010-9257-9 PG 11 WC Psychology, Clinical SC Psychology GA 628OE UT WOS:000280129000007 PM 20232131 ER PT J AU Aguilar, D Chan, WY Bozkurt, B Ramasubbu, K Deswal, A AF Aguilar, David Chan, Wenyaw Bozkurt, Biykem Ramasubbu, Kumudha Deswal, Anita TI Metformin Use and Mortality in Ambulatory Patients With Diabetes and Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 [Aguilar, David; Bozkurt, Biykem; Ramasubbu, Kumudha; Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA. [Aguilar, David; Bozkurt, Biykem; Ramasubbu, Kumudha; Deswal, Anita] Michael E Debakey Med Ctr, Houston, TX USA. [Chan, Wenyaw] Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2010 VL 16 IS 8 SU 1 MA 272 BP S83 EP S84 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645YJ UT WOS:000281501800272 ER PT J AU Aleong, R Sauer, WH Pellegnni, CN Yang, YF Keung, E Heidenreich, P Rumsfeld, JS Massie, BM Varosy, PD AF Aleong, Ryan Sauer, William H. Pellegnni, Cara N. Yang, Yanfei Keung, Edmund Heidenreich, Paul Rumsfeld, John S. Massie, Barry M. Varosy, Paul D. TI Clinical Subtype of Atrial Fibrillation at the Time of Implantation and Subsequent Mortality among Veterans With Implantable Defibrillators SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 [Aleong, Ryan; Sauer, William H.; Rumsfeld, John S.; Varosy, Paul D.] Univ Colorado Denver, Aurora, CO USA. [Pellegnni, Cara N.; Yang, Yanfei; Keung, Edmund; Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Pellegnni, Cara N.; Yang, Yanfei; Keung, Edmund; Massie, Barry M.] UCSF, San Francisco, CA USA. [Heidenreich, Paul] Palo Alto VAMC, Palo Alto, CA USA. [Heidenreich, Paul] Stanford Univ, Palo Alto, CA 94304 USA. [Rumsfeld, John S.; Varosy, Paul D.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2010 VL 16 IS 8 SU 1 MA 185 BP S58 EP S58 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645YJ UT WOS:000281501800186 ER PT J AU Deswal, A Richardson, P Bozkurt, B Mann, DL AF Deswal, Anita Richardson, Peter Bozkurt, Biykem Mann, Douglas L. TI Randomized Trial of Aldosterone AntagonisM in Diastolic Heart Failure (RAAM-DHF) SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 [Deswal, Anita; Richardson, Peter; Bozkurt, Biykem] VA Med Ctr, Houston, TX USA. [Deswal, Anita; Richardson, Peter; Bozkurt, Biykem] Baylor Coll Med, Houston, TX 77030 USA. [Mann, Douglas L.] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2010 VL 16 IS 8 SU 1 MA 017 BP S7 EP S7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645YJ UT WOS:000281501800018 ER PT J AU Lewis, GD Murphy, RM Shah, R Pappagianopoulos, PP Malhotra, R Bloch, KD Systrom, DM Semigran, MJ AF Lewis, Gregory D. Murphy, Ryan M. Shah, Ravi Pappagianopoulos, Paul P. Malhotra, Rajeev Bloch, Kenneth D. Systrom, David M. Semigran, Marc J. TI Right Ventricular and Pulmonary Vascular Response Patterns To Exercise Predict Exercise Capacity and Outcomes in Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 [Lewis, Gregory D.; Murphy, Ryan M.; Shah, Ravi; Pappagianopoulos, Paul P.; Malhotra, Rajeev; Bloch, Kenneth D.; Systrom, David M.; Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2010 VL 16 IS 8 SU 1 MA 007 BP S3 EP S3 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645YJ UT WOS:000281501800008 ER PT J AU Mather, P Alexis, J Sheppard, R Thohan, V Markham, D Dec, GW Liu, P McNamara, D AF Mather, Paul Alexis, Jeffrey Sheppard, Richard Thohan, Vinay Markham, David Dec, G. William Liu, Peter McNamara, Dennis TI Impact of Blood Pressure on Myocardial Recovery and Outcomes in Recent Onset Cardiomyopathy: Results of IMAC2 SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 [Mather, Paul] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Alexis, Jeffrey] Univ Rochester, Rochester, NY USA. [Sheppard, Richard] McGill SMBD Jewish Gen, Montreal, PQ, Canada. [Thohan, Vinay] Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC 27109 USA. [Markham, David] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Dec, G. William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liu, Peter] Univ Toronto, Toronto, ON, Canada. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2010 VL 16 IS 8 SU 1 MA 314 BP S95 EP S95 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645YJ UT WOS:000281501800313 ER PT J AU Moslehi, J Minamishima, YA Padera, R Liao, R Kaelin, WG AF Moslehi, Javid Minamishima, Yoji Andy Padera, Robert Liao, Ronglih Kaelin, William G. TI Loss of PHD Prolyl Hydroxylase Activity in Cardiomyocytes Phenocopies Ischemic Cardiomyopathy SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 [Moslehi, Javid; Padera, Robert] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Moslehi, Javid; Minamishima, Yoji Andy; Liao, Ronglih; Kaelin, William G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kaelin, William G.] Howard Hughes Med Inst, Chevy Chase, MD USA. RI Minamishima, Yoji/E-5380-2010 OI Minamishima, Yoji/0000-0001-7995-9318 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2010 VL 16 IS 8 SU 1 MA 004 BP S2 EP S2 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645YJ UT WOS:000281501800005 ER PT J AU Subramanian, D Subramanian, V Deswal, A Mann, DL AF Subramanian, Devika Subramanian, Venkataraman Deswal, Anita Mann, Douglas L. TI Improved Predictive Models of Mortality in Chronic Heart Failure Using Time-Series Measurements of Inflammatory Biomarkers SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 Rice Univ, Houston, TX USA. Univ Nottingham Hosp, Nottingham NG7 2UH, England. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2010 VL 16 IS 8 SU 1 MA 307 BP S93 EP S93 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645YJ UT WOS:000281501800306 ER PT J AU Thomas, MK Weaver, C LaCroix, B Prokunina-Olsson, M Hall, JL AF Thomas, Melissa K. Weaver, Cyprian LaCroix, Bonnie Prokunina-Olsson, Mila Hall, Jennifer L. TI Defining the Role of the Transcription Factor TCF7L2 in Type 2 Diabetes SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 14th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 12-15, 2010 CL San Diego, CA SP Heart Failure Soc Amer C1 Mass Gen Hosp, Boston, MA USA. Univ Minnesota, Lillehei Heart Inst, Minneapolis, MN USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2010 VL 16 IS 8 SU 1 MA 113 BP S37 EP S37 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645YJ UT WOS:000281501800114 ER PT J AU Ehrenfeld, JM Mulvoy, W Sandberg, WS AF Ehrenfeld, Jesse M. Mulvoy, William Sandberg, Warren S. TI Performance Comparison of Right- and Left-Sided Double-Lumen Tubes Among Infrequent Users SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE lung isolation; equipment safety; anesthesia; intubation; intratracheal; respiration; artificial; thoracic surgical procedures ID THORACIC-SURGERY; ENDOTRACHEAL-TUBES AB Objective: To compare performance of right- versus left-sided double-lumen tubes (DLTs) among infrequent users by evaluating the incidence and severity of hypoxemia, hypercapnia, and high airway pressures. Design: A retrospective, cohort study. Setting: A university hospital. Participants: Ninety-eight patients undergoing left-sided DLT placement (53.9 +/- 21.2 years old) and 98 patients undergoing right-sided DLT placement (62.3 +/- 20.6 years old). Cases performed by thoracic anesthesia specialists were excluded. Interventions: The authors retrospectively reviewed electronic anesthetic records from a 2-year period to determine the incidence and severity of hypoxia (SpO(2) < 90%), hypercapnia (end-tidal carbon dioxide > 45 mmHg) and high airway pressures (peak inspiratory pressure >35 cmH(2)O) during one-lung ventilation via right and left DLTs. Measurements and Main Results: Right-sided (n = 98) DLTs were almost exclusively used on the side contralateral to surgery by infrequent users, whereas left-sided (n = 98) DLTs were used for ipsilateral surgery one third of the time. Hypoxia lasted longer in left versus right DLTs, but the frequency of hypoxia was the same for each tube type among infrequent users. Hypercapnia and high airway pressures occurred more frequently with left-sided DLTs. Conclusions: Left-sided DLTs are perceived to be safer because they may be less prone to malpositioning during lung isolation. However, the supposition that left-sided DLTs are safer than right-sided DLTs when intraoperative hypoxia, hypercapnia, and high airway pressures are used as criteria, even when these tubes are used by infrequent users, is not supported by the data. (C) 2010 Elsevier Inc. All rights reserved. C1 [Ehrenfeld, Jesse M.; Mulvoy, William; Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Ehrenfeld, JM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Jackson 460, Boston, MA 02114 USA. EM jehrenfeld@partners.org OI Ehrenfeld, Jesse/0000-0003-3427-0140; Sandberg, Warren/0000-0002-9246-777X NR 9 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD AUG PY 2010 VL 24 IS 4 BP 598 EP 601 DI 10.1053/j.jvca.2009.09.007 PG 4 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 636IS UT WOS:000280726000010 PM 19942453 ER PT J AU Xavier, A Erlich, J Lerner, AB AF Xavier, Andrea Erlich, Jason Lerner, Adam B. TI Coronary Artery Bypass Graft Surgery and Moderate Aortic Stenosis: When To Leave Well Enough Alone SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE aortic stenosis; coronary artery bypass graft surgery; aortic valve replacement; transesophageal; echocardiography; combined aortic valve replacement/coronary artery bypass graft surgery C1 [Xavier, Andrea; Erlich, Jason; Lerner, Adam B.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Lerner, AB (reprint author), BIDMC, Dept Anesthesia, 1 Deaconess Rd,CC 470, Boston, MA 02215 USA. EM alerner@bidmc.harvard.edu NR 0 TC 0 Z9 0 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD AUG PY 2010 VL 24 IS 4 BP 712 EP 713 DI 10.1053/j.jvca.2010.05.001 PG 2 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 636IS UT WOS:000280726000027 PM 20673750 ER PT J AU Prystowsky, EN Camm, J Lip, GYH Allessie, M Bergmann, JF Breithardt, G Brugada, J Crijns, H Ellinor, PT Mark, D Naccarelli, G Packer, D Tamargo, J AF Prystowsky, Eric N. Camm, John Lip, Gregory Y. H. Allessie, Maurits Bergmann, Jean-Francois Breithardt, Guenter Brugada, Josep Crijns, Harry Ellinor, Patrick T. Mark, Daniel Naccarelli, Gerald Packer, Douglas Tamargo, Juan TI The Impact of New and Emerging Clinical Data on Treatment Strategies for Atrial Fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; stroke; thromboembolism; heart failure; catheter ablation ID RADIOFREQUENCY CATHETER ABLATION; RISK STRATIFICATION SCHEMES; CONGESTIVE-HEART-FAILURE; STROKE PREVENTION; ANTITHROMBOTIC THERAPY; ANTICOAGULANT-THERAPY; CARDIOVASCULAR EVENTS; COST-EFFECTIVENESS; CONTROLLED-TRIAL; UNITED-STATES AB AF Treatment Strategies. Introduction: The Atrial Fibrillation (AF) Exchange Group, an international multidisciplinary group concerned with the management of AF, was convened to review recent advances in the field and the potential impact on treatment strategies. Methods: Issues discussed included epidemiology and the impact of the rising incidence of AF on health care systems, developments in pharmacological and surgical interventions in the management of arrhythmias and thromboprophylaxis, the potential to affect treatment strategies, and barriers to implementing them. Results: The incidence of AF and the associated burden on health care systems are increasing with aging populations, prevalence of comorbidities and more effective treatment of cardiovascular diseases. Advances in available medical treatments, in particular dronedarone and dabigatran, with other products in development, offer the possibility of changes in treatment paradigms and a greater emphasis on reducing hospitalizations and improvement in long-term outcomes instead of a symptom/safety-driven approach in which the priority is symptom suppression without provoking drug toxicity. Developments in catheter ablation techniques may mean that, in experienced centers, ablation may be offered as first-line treatment in selected patient populations. Barriers to optimal treatment include underdiagnosis, lack of recognition as a serious condition and as a risk factor for stroke, limited access to care, inadequate implementation of guidelines, and poor adherence to treatment. Conclusions: The focus of the management of AF may be changing as a consequence of new treatments based on the outcome improvements they offer. However, the benefits will not be fully realized if guidelines and guidance are not observed in routine clinical practice. (J Cardiovasc Electrophysiol, Vol. 21, pp. 946-958, August 2010) C1 [Prystowsky, Eric N.] Care Grp, Indianapolis, IN 46260 USA. [Camm, John] St Georges Univ London, London, England. [Lip, Gregory Y. H.] Univ Birmingham, Ctr Cardiovasc Sci, City Hosp, Birmingham, W Midlands, England. [Allessie, Maurits] Univ Maastricht, Dept Physiol, Maastricht, Netherlands. [Bergmann, Jean-Francois] Hop Lariboisiere, Serv Med Interne A, F-75475 Paris, France. [Bergmann, Jean-Francois; Breithardt, Guenter] Hosp Univ Munster, Dept Cardiol & Angiol, Munster, Germany. [Brugada, Josep] Univ Barcelona, Hosp Clin, Cardiovasc Inst, Arrhythmia Sect, Barcelona, Spain. [Crijns, Harry] Univ Hosp Maastricht, Dept Cardiol, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Mark, Daniel] Duke Univ, Med Ctr, Dept Med Cardiovasc Med, Durham, NC USA. [Naccarelli, Gerald] Penn State Heart & Vasc Inst, Div Cardiol, Hershey, PA USA. [Packer, Douglas] Mayo Clin, Rochester, MN USA. [Tamargo, Juan] Univ Complutense Madrid, Fac Med, Dept Pharmacol, E-28040 Madrid, Spain. RP Prystowsky, EN (reprint author), Care Grp, 8333 Naab Rd,Suite 400, Indianapolis, IN 46260 USA. EM eprystow@TheCareGroup.com RI Tamargo, Juan/J-7772-2016; OI Tamargo, Juan/0000-0002-7979-7758; Mark, Daniel/0000-0001-6340-8087; BRUGADA, JOSEP/0000-0002-5662-8302 FU Sanofi-aventis; Daiichi; Pfizer; BMS; Cardiome; Merck; Astellas; Astra Zeneca; Biotronic; Alexion Pharmaceuticals; Eli Lilly; Proctor Gamble; Medtronic; Medicure; Innocoll; St. Jude Medical; Glaxo Smith Kline; Boehringer-Ingelheim; Boston Scientific; Bristol Myers Squibb; Portola; Otsuka; Gilead; Novartis; Xention; Biocritique; Biosense Webster; Cryocath; Siemens USA FX E. Prystowsky reports participation in a new antiarrhythmic drug study supported by Sanofi-aventis and consultancy for the same; he consults for Boehringer-Ingelheim; he has received honoraria relevant to this topic. J. Camm reports participation in multicenter trials supported by Daiichi, Pfizer, BMS, Cardiome, and Merck; he received compensation for participation on a speaker's bureau from Sanofi-aventis, Cardiome, Merck, and Astellas; he serves as a consultant or on the advisory boards of Merck, Sanofi-aventis, Boehringer-Ingelheim, Daiichi, and Medtronic. G. Lip reports participation in research studies supported by Astellas, Astra Zeneca, Biotronic, Cardiome; he serves as a consultant or on the advisory boards of Bayer, Astellas, Astra Zeneca, Sanofi-aventis, Biotronic, Cardiome, Boehringer-Ingelheim. M. Allessie reports compensation on a speakers bureau, but did not name the sponsor. J.-F. Bergmann reports honoraria from Sanofi-aventis and Glaxo H. Crijns reports participation on a research grant supported by Sanofi-aventis, as well as participation on a speakers bureau and serving as a consultant or on the advisory board of that company. P. Ellinor reports participation on multiple research grants, including CHS, FHS, Rotterdam, MONICA/KORA, and PREVENT-IT studies; he serves as a consultant or on the advisory boards of Sanofi-aventis and Ortho-MacNeil. D. Mark reports participation on research grants supported by Alexion Pharmaceuticals, Eli Lilly, Proctor & Gamble, Pfizer, Medtronic, Medicure, Innocoll, and St. Jude Medical; he serves as a consultant or on the advisory board of Sanofi-aventis. G. Naccarelli reports participation on research grants supported by Glaxo Smith Kline, Boehringer-Ingelheim, Boston Scientific, and Sanofi-aventis; he has received consultant fees or honoraria from Sanofi-aventis, St. Jude Medical, Bristol Myers Squibb, Merck, Portola, Otsuka, Boehringer-Ingelheim, Pfizer, Astra Zeneca, Medtronic, Gilead, Cardiome, Novartis, Xention, Astellas, Glaxo Smith Kline, and Biocritique. D. Packer reports participation on research grants supported by St. Jude Medical, Biosense Webster, Boston Scientific, Medtronic, Cryocath, and Siemens USA; he serves as a consultant or on the advisory boards of Medtronic, St. Jude Medical, Siemans, Sanofi-aventis, Biosense Webster, and Cryocath; he reports a patent on mapping technology. J. Tamargo reports speakers bureau fees and honoraria, as well as serving as a consultant or on advisory board, but does not name the sponsors/companies. NR 80 TC 17 Z9 18 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD AUG PY 2010 VL 21 IS 8 BP 946 EP 958 DI 10.1111/j.1540-8167.2010.01770.x PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 635MX UT WOS:000280660900023 PM 20384658 ER PT J AU Benson, EK Lee, SW Aaronson, SA AF Benson, Erica K. Lee, Sam W. Aaronson, Stuart A. TI Role of progerin-induced telomere dysfunction in HGPS premature cellular senescence SO JOURNAL OF CELL SCIENCE LA English DT Article DE Cellular senescence; DNA damage; Nuclear lamins; Telomerase; Telomere dysfunction; Tumor suppressors ID HUTCHINSON-GILFORD-PROGERIA; LAMIN-A; NUCLEAR ARCHITECTURE; HUMAN FIBROBLASTS; INSTABILITY SYNDROMES; GENOMIC INSTABILITY; STEM-CELLS; HUMAN SKIN; DNA; MUTANT AB Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature-aging syndrome caused by a dominant mutation in the gene encoding lamin A, which leads to an aberrantly spliced and processed protein termed progerin. Previous studies have shown that progerin induces early senescence associated with increased DNA-damage signaling and that telomerase extends HGPS cellular lifespan. We demonstrate that telomerase extends HGPS cellular lifespan by decreasing progerin-induced DNA-damage signaling and activation of p53 and Rb pathways that otherwise mediate the onset of premature senescence. We show further that progerin-induced DNA-damage signaling is localized to telomeres and is associated with telomere aggregates and chromosomal aberrations. Telomerase amelioration of DNA-damage signaling is relatively rapid, requires both its catalytic and DNA-binding functions, and correlates in time with the acquisition by HGPS cells of the ability to proliferate. All of these findings establish that HGPS premature cellular senescence results from progerin-induced telomere dysfunction. C1 [Benson, Erica K.; Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10012 USA. [Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Aaronson, SA (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, Box 1130,1 Gustave L Levy Pl, New York, NY 10012 USA. EM stuart.aaronson@mssm.edu FU NCI [PO1CA80058, T32 CA078207]; New York State Stem Cell [C024313]; NIGMS [T32 GM008553]; NIH-NCI [5R24 CA095823-04]; NSF [DBI-9724504]; NIH [1 S10 RR0 9145-01] FX This work was supported by grant number PO1CA80058 from the NCI and the New York State Stem Cell contract #C024313. E. B. was supported by the NCI Training Program in Cancer Biology (T32 CA078207) and the NIGMS Training Program in Cellular and Molecular Biology (T32 GM008553). Confocal laser scanning microscopy was performed at the MSSM-Microscopy Shared Resource Facility, supported with funding from NIH-NCI shared resources grant (5R24 CA095823-04), NSF Major Research Instrumentation grant (DBI-9724504) and NIH shared instrumentation grant (1 S10 RR0 9145-01). We thank Elizabeth Blackburn (UCSF) for providing us with TERT mutant constructs, N125A+T126A and D868A, in the pBABE-puro backbone. We thank Titia de Lange (Rockefeller University) for the TRF1 (#370) antibody and for a TRF2Delta B Delta M construct obtained via Addgene. We also thank Bo Zhao and Cesar Munoz-Fontela for helpful discussions. Deposited in PMC for release after 12 months. NR 65 TC 56 Z9 60 U1 0 U2 15 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG 1 PY 2010 VL 123 IS 15 BP 2605 EP 2612 DI 10.1242/jcs.067306 PG 8 WC Cell Biology SC Cell Biology GA 629CN UT WOS:000280172000009 PM 20605919 ER PT J AU Young, AP Wagers, AJ AF Young, Arthur P. Wagers, Amy J. TI Pax3 induces differentiation of juvenile skeletal muscle stem cells without transcriptional upregulation of canonical myogenic regulatory factors SO JOURNAL OF CELL SCIENCE LA English DT Article DE Pax3; Pax7; Muscle stem cells; Satellite cells; C2C12; Myogenic differentiation; Myogenic regulatory factors ID SATELLITE CELLS; PROGENITOR CELLS; PRECURSOR CELLS; SELF-RENEWAL; GENE MYF-5; MYOD; EXPRESSION; MICE; LIMB; SPECIFICATION AB Pax3 is an essential myogenic regulator of fetal and embryonic development, but its role in postnatal myogenesis remains a topic of debate. We show that constitutive expression of Pax3 in postnatal, juvenile mouse skeletal muscle stem cells, a subset of the heterogeneous satellite cell pool highly enriched for myogenic activity, potently induces differentiation. This differentiation-promoting activity stands in contrast to the differentiation-inhibiting effects of Pax3 in the commonly used mouse myoblast cell line C2C12. Pax3 mRNA levels in distinct muscles correlate with the rate of myogenic differentiation of their muscle stem cells. Although Pax3 controls embryonic myogenesis through regulation of the canonical myogenic regulatory factors (MRFs) Myf-5, MyoD, myogenin and Mrf4, we find that in postnatal muscle stem cells, ectopic Pax3 expression fails to induce expression of any of these factors. Unexpectedly, overexpression of neither Myf-5 nor myogenin is sufficient to induce differentiation of juvenile stem cells; and knockdown of Myf-5, rather than inhibiting differentiation, promotes it. Taken together, our results suggest that there are distinct myogenic regulatory pathways that control the embryonic development, juvenile myogenesis and adult regeneration of skeletal myofibers. C1 [Young, Arthur P.; Wagers, Amy J.] Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02115 USA. [Young, Arthur P.; Wagers, Amy J.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Young, Arthur P.; Wagers, Amy J.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Wagers, AJ (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02115 USA. EM amy.wagers@joslin.harvard.edu FU Burroughs Wellcome Fund; Beckman Foundation; NIH/NIDDK [T32 DK07260-30] FX We thank Joyce LaVecchio and Girijesh Buruzula at the JDC/HSCI Flow Core for cell sorting and flow cytometry analysis, Jennifer Shadrach for laboratory management, Andrew Lassar for provision of cDNAs, and Andrew Brack and Andrew Lassar for critically reviewing the manuscript. This work was supported in part by a Burroughs Wellcome Fund career award (A.J.W.), Beckman Foundation Young Investigators Award, and NIH/NIDDK training grant T32 DK07260-30 (A.P.Y.). Deposited in PMC for release after 12 months. NR 47 TC 23 Z9 23 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG 1 PY 2010 VL 123 IS 15 BP 2632 EP 2639 DI 10.1242/jcs.061606 PG 8 WC Cell Biology SC Cell Biology GA 629CN UT WOS:000280172000012 PM 20605921 ER PT J AU Mancuso, E Faro, A Joshi, G Geller, DA AF Mancuso, Elizabeth Faro, Alyssa Joshi, Gagan Geller, Daniel A. TI Treatment of Pediatric Obsessive-Compulsive Disorder: A Review SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Review ID SEROTONIN REUPTAKE INHIBITORS; COGNITIVE-BEHAVIORAL THERAPY; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; NEUROPSYCHIATRIC DISORDERS; STREPTOCOCCAL INFECTIONS; CLOMIPRAMINE TREATMENT; PSYCHIATRIC-DISORDERS; TOURETTES-SYNDROME; MULTICENTER TRIAL AB Recently, research in pediatric obsessive-compulsive disorder (OCD) has expanded to include large family genetic studies, elaboration of phenotypic dimensions, description of co-morbid disorders and their moderating effects on treatment response and outcome, research on immune-based neuropsychiatric causes, randomized controlled trials of selective serotonin re-uptake inhibitors (SSRIs), randomized controlled trials of cognitive behavioral therapy (CBT), comparative treatment trials; new approaches in behavior therapy, and increased awareness of newer approaches to treatment. The purpose of this article is to review assessment and treatment strategies to include current advances in research. C1 [Mancuso, Elizabeth; Faro, Alyssa; Joshi, Gagan; Geller, Daniel A.] Massachusetts Gen Hosp, Dept Psychiat, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Geller, Daniel A.] Harvard Univ, Sch Med, Boston, MA USA. RP Geller, DA (reprint author), Massachusetts Gen Hosp, Pediat OCD Program, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM dageller@partners.org FU Boehringer Ingelheim; Otsuka; Eli Lilly; Pediatric Obsessive-compulsive and Related Disorders fund; Eli Lilly and Co.; Forest Laboratories; Glaxo-SmithKline; Pfizer; Ethel DuPont Warren Fellowship; American Academy of Child and Adolescent Psychiatry [2005]; National Institute of Mental Health; McNeil Pediatrics; SynerMed Communications; Bristol Myers Squibb; Glaxo Smith Kline; Shire; Johnson Johnson; Merck; Cephlon; McNeil; Eli-Lily; Abbott; Novartis; Organon; Takeda; New River Pharmaceuticals FX Dr. Daniel Geller receives/d in last 36 months (to April 2010) research support from Boehringer Ingelheim, Otsuka, Eli Lilly, Pediatric Obsessive-compulsive and Related Disorders fund (philanthropic); speaker honoraria from Eli Lilly; is on the Medical Advisory Boards/Consulting for Eli Lilly; private foundations, McIngvale Family Foundation, National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Institute of Mental Health. He has receives/d lifetime research support from Eli Lilly and Co., Forest Laboratories, GlaxoSmithKline, Pfizer, Boehringer Ingelheim, Otsuka; speaker honoraria from Alza, Bristol-Myers-Squibb, Eli Lilly, Forest Laboratories, Glaxo-SmithKline, Novartis, Pfizer, Shire, Wyeth; is on the Medical Advisory Boards/Consulting for Eli Lilly, Solvay, Lundbeck, and Glaxo-SmithKline; private foundations, Obsessive-compulsive Foundation, Tourette Syndrome Association, Wallace Foundation, McIngvale Family Foundation Rogers Memorial Hospital; educational consultant/guest lecture for American Psychiatric Publishing: honorarium for textbook Network for Continuing Medical; education, Neuroscience e journal club lecturer; National Institutes of Health, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke. Gagan Joshi has received the Ethel DuPont Warren Fellowship Award 2005-2006, Pilot Research Award from the American Academy of Child and Adolescent Psychiatry 2005, National Institute of Mental Health (reviewer and member of the NIMH Editorial Board), McNeil Pediatrics (CME sponsored by SynerMed Communications), Bristol Myers Squibb (Site PI for Multi-centered Trial), Glaxo Smith Kline (Site PI for Multi-centered Trial), Shire (member of national advisory board), Subinvestigator for clinical trials sponsored by Shire, Johnson & Johnson, Pfizer, Merck, Cephlon, McNeil, Eli-Lily, Abbott, Novartis, Bristol Myers Squibb, Organon, Otsuka, Takeda, & New River Pharmaceuticals. Elizabeth Mancuso and Alyssa Faro have no conflicts of interest or financial ties to disclose. NR 97 TC 15 Z9 17 U1 9 U2 25 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD AUG PY 2010 VL 20 IS 4 SI SI BP 299 EP 308 DI 10.1089/cap.2010.0040 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 645FG UT WOS:000281435700008 PM 20807068 ER PT J AU Preis, SR Massaro, JM Hoffmann, U D'Agostino, RB Levy, D Robins, SJ Meigs, JB Vasan, RS O'Donnell, CJ Fox, CS AF Preis, Sarah Rosner Massaro, Joseph M. Hoffmann, Udo D'Agostino, Ralph B., Sr. Levy, Daniel Robins, Sander J. Meigs, James B. Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Neck Circumference as a Novel Measure of Cardiometabolic Risk: The Framingham Heart Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VISCERAL ADIPOSE-TISSUE; FATTY-ACID-METABOLISM; INSULIN-RESISTANCE; SLEEP-APNEA; ASSOCIATION; OBESITY; HYPERTENSION; CHOLESTEROL; POPULATION; COMMUNITY AB Background: Neck circumference, a proxy for upper-body sc fat, may be a unique fat depot that confers additional cardiovascular risk above and beyond central body fat. Methods and Results: Participants with neck circumference measures who underwent multidetector computed tomography to assess visceral adipose tissue (VAT) were included [n = 3307, 48% women; mean age = 51 yr; mean body mass index (BMI) = 27.8 kg/m(2); mean neck circumference = 40.5 cm (men) and 34.2 cm (women)]. Sex-specific linear regression models were used to assess the association between SD increase in neck circumference and cardiovascular disease (CVD) risk factors (systolic and diastolic blood pressure; total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglycerides; and fasting plasma glucose, insulin, proinsulin, and homeostasis model assessment of insulin resistance). Neck circumference was correlated with VAT [r = 0.63 (men); r = 0.74 (women); P < 0.001] and BMI [r = 0.79 (men); r = 0.80 (women); P < 0.001]. After further adjustment for VAT, neck circumference was positively associated with systolic blood pressure, diastolic blood pressure in men only, triglycerides, fasting plasma glucose in women only, insulin, proinsulin, and homeostasis model assessment of insulin resistance and was inversely associated with high-density lipoprotein (all P values < 0.01). Similar results were observed in models that adjusted for both VAT and BMI. In a secondary analysis of incident CVD as an outcome, there was no statistically significant association observed for neck circumference in multivariable-adjusted models. Conclusions: Neck circumference is associated with CVD risk factors even after adjustment for VAT and BMI. These findings suggest that upper-body sc fat may be a unique, pathogenic fat depot. (J Clin Endocrinol Metab 95: 3701-3710, 2010) C1 [Preis, Sarah Rosner; D'Agostino, Ralph B., Sr.; Levy, Daniel; Robins, Sander J.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham, MA 01702 USA. [Preis, Sarah Rosner; D'Agostino, Ralph B., Sr.; Levy, Daniel; Robins, Sander J.; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] Boston Univ, Framingham Heart Study, Framingham, MA 01702 USA. [Preis, Sarah Rosner; Levy, Daniel; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20824 USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02114 USA. [Robins, Sander J.; Vasan, Ramachandran S.] Massachusetts Gen Hosp, Sect Prevent Med, Boston, MA 02114 USA. [Robins, Sander J.; Vasan, Ramachandran S.] Massachusetts Gen Hosp, Serv Cardiol, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Preis, Sarah/0000-0002-9360-4166; Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; American Diabetes Association FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195) and by an American Diabetes Association Career Development Award (to J.B.M.). NR 31 TC 94 Z9 108 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2010 VL 95 IS 8 BP 3701 EP 3710 DI 10.1210/jc.2009-1779 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635JW UT WOS:000280652400021 PM 20484490 ER PT J AU Beckman, JA Goldfine, AB Goldin, A Prsic, A Kim, S Creager, MA AF Beckman, Joshua A. Goldfine, Allison B. Goldin, Alison Prsic, Adnan Kim, Sora Creager, Mark A. TI Inhibition of Protein Kinase C beta Does Not Improve Endothelial Function in Type 2 Diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PERIPHERAL NEUROPATHY; CLINICAL-TRIAL; RUBOXISTAURIN; MELLITUS; RATS; VASODILATION; ACTIVATION; DILATION; LY333531; OXYGEN AB Context: Antagonism of protein kinase C beta (PKC beta) restores endothelial function in experimental models of diabetes and prevents vascular dysfunction in response to hyperglycemia in healthy humans. Objective: We tested the hypothesis that PKC beta antagonism would improve vascular function in subjects with type 2 diabetes compared with healthy control subjects. Design: The effect of PKC beta was evaluated in a randomized, placebo-controlled, double-blinded crossover trial. Setting: The study was performed in the outpatient setting of a university medical center. Participants: Thirteen subjects with type 2 diabetes without evidence of cardiovascular disease and 15 healthy control subjects were recruited via newspaper advertisement. Intervention: Subjects underwent a randomized, double-blind, crossover, placebo-controlled trial of the selective PKC beta antagonist ruboxistaurin mesylate. Subjects received each treatment for 14 d. Main Outcome Measure: Endothelium-dependent and endothelium-independent vasodilation of forearm resistance vessels was measured with mercury-in-silastic, strain-gauge plethysmography during intraarterial administration of methacholine chloride and verapamil, respectively. Markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress were measured after each treatment. Results: Endothelium-dependent vasodilation of forearm resistance vessels was attenuated in diabetic subjects when compared with healthy subjects (P = 0.001). Endothelium-independent vasodilation did not differ between groups (P value not significant). Ruboxistaurin did not significantly change endothelium-dependent or endothelium-independent vasodilation or blood-based markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress in either diabetic or healthy subjects. Conclusion: Endothelial dysfunction of forearm resistance vessels was not improved by 2 wk of selective PKC beta inhibition in patients with diabetes. These results suggest that PKC beta does not contribute significantly to vascular dysfunction in otherwise healthy patients with type 2 diabetes. (J Clin Endocrinol Metab 95: 3783-3787, 2010) C1 [Beckman, Joshua A.; Goldin, Alison; Prsic, Adnan; Kim, Sora; Creager, Mark A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Div Cellular & Mol Physiol, Boston, MA 02215 USA. RP Beckman, JA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM jbeckman@partners.org OI Beckman, Joshua/0000-0001-8332-8439 FU NIH [P01 HL48743, K23 HL-04169]; American Diabetes Association [ADA 1-06-CD-01]; Eli Lilly FX This work has been supported by grants from the NIH (P01 HL48743 and K23 HL-04169), the American Diabetes Association (ADA 1-06-CD-01), and Eli Lilly. M. A. C. is the Simon C. Fireman Scholar in Cardiovascular Medicine at Brigham and Women's Hospital. NR 20 TC 15 Z9 16 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2010 VL 95 IS 8 BP 3783 EP 3787 DI 10.1210/jc.2010-0286 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635JW UT WOS:000280652400033 PM 20444914 ER PT J AU Roth, MY Page, ST Lin, K Anawalt, BD Matsumoto, AM Snyder, CN Marck, BT Bremner, WJ Amory, JK AF Roth, M. Y. Page, S. T. Lin, K. Anawalt, B. D. Matsumoto, A. M. Snyder, C. N. Marck, B. T. Bremner, W. J. Amory, J. K. TI Dose-Dependent Increase in Intratesticular Testosterone by Very Low-Dose Human Chorionic Gonadotropin in Normal Men with Experimental Gonadotropin Deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE ANTAGONIST; MASS-SPECTROMETRY; HEALTHY-YOUNG; INFERTILE MEN; HUMAN TESTIS; SPERMATOGENESIS; MAINTENANCE; DIHYDROTESTOSTERONE; SUPPRESSION; FLUID AB Context and Objective: In men with infertility secondary to gonadotropin deficiency, treatment with relatively high dosages of human chorionic gonadotropin (hCG) stimulates intratesticular testosterone (IT-T) biosynthesis and spermatogenesis. Previously we found that lower dosages of hCG stimulated IT-T to normal. However, the minimal dose of hCG needed to stimulate IT-T and the dose-response relationship between very low doses of hCG and IT-T and serum testosterone in normal men is unknown. Design, Setting, Patients, and Intervention: We induced experimental gonadotropin deficiency in 37 normal men with the GnRH antagonist acyline and randomized them to receive one of four low doses of hCG: 0, 15, 60, or 125 IU sc every other day or 7.5 g daily testosterone gel for 10 d. Testicular fluid was obtained by percutaneous aspiration for steroid measurements at baseline and after 10 d of treatment and correlated with contemporaneous serum hormone measurements. Results: Median (25th, 75th percentile) baseline IT-T was 2508 nmol/liter (1753, 3502 nmol/liter). IT-T concentrations increased in a dose-dependent manner with very low-dosage hCG administration from 77 nmol/liter (40, 122 nmol/liter) to 923 nmol/liter (894, 1017 nmol/liter) in the 0- and 125-IU groups, respectively (P < 0.001). Moreover, serum hCG was significantly correlated with both IT-T and serum testosterone (P < 0.01). Conclusion: Doses of hCG far lower than those used clinically increase IT-T concentrations in a dose-dependent manner in normal men with experimental gonadotropin deficiency. Assessment of IT-T provides a valuable tool to investigate the hormonal regulation of spermatogenesis in man. (J Clin Endocrinol Metab 95: 3806-3813, 2010) C1 [Roth, M. Y.; Page, S. T.; Anawalt, B. D.; Matsumoto, A. M.; Snyder, C. N.; Bremner, W. J.; Amory, J. K.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Lin, K.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Roth, M. Y.; Page, S. T.; Anawalt, B. D.; Matsumoto, A. M.; Snyder, C. N.; Bremner, W. J.; Amory, J. K.] Univ Washington, Ctr Res Reprod & Contracept, Seattle, WA 98195 USA. [Matsumoto, A. M.; Marck, B. T.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. RP Roth, MY (reprint author), Univ Washington, Dept Med, 1959 NE Pacific St,Box 357138, Seattle, WA 98195 USA. EM mylang@u.washington.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U54-HD-12629, U54-HD-42454]; Diabetes, Obesity, and Metabolism Grant [T32 DK007247]; Department of Veterans Affairs; National Institute of Aging, a division of the National Institutes of Health [K23 AG027238] FX This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through cooperative agreements U54-HD-12629 and U54-HD-42454 as part of the specialized Cooperative Centers Program in Reproductive Research and the Cooperative Contraceptive Research Centers Program. M.Y.R. is supported by the Diabetes, Obesity, and Metabolism Grant T32 DK007247. A. M. M. is supported by the Department of Veterans Affairs. S. T. P. is supported by Grant K23 AG027238 from the National Institute of Aging, a division of the National Institutes of Health. NR 23 TC 20 Z9 20 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2010 VL 95 IS 8 BP 3806 EP 3813 DI 10.1210/jc.2010-0360 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635JW UT WOS:000280652400036 PM 20484472 ER PT J AU Lima, MMO Pareja, JC Alegre, SM Geloneze, SR Kahn, SE Astiarraga, BD Chaim, EA Geloneze, B AF Lima, Marcelo M. O. Pareja, Jose C. Alegre, Sarah M. Geloneze, Sylka R. Kahn, Steven E. Astiarraga, Brenno D. Chaim, Elinton A. Geloneze, Bruno TI Acute Effect of Roux-En-Y Gastric Bypass on Whole-Body Insulin Sensitivity: A Study with the Euglycemic-Hyperinsulinemic Clamp SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TYPE-2 DIABETIC SUBJECTS; BETA-CELL FUNCTION; BARIATRIC SURGERY; WEIGHT-LOSS; OBESE-PATIENTS; METABOLIC SYNDROME; MORBID-OBESITY; RESISTANCE; RESTORATION; ADIPONECTIN AB Context: Insulin resistance ameliorates after bariatric surgery, yet there is still a need for data on the acute effect of Roux-en-Y gastric bypass (RYGBP) on insulin sensitivity. Objective: The objective of the study was to describe the acute effect of RYGBP on insulin sensitivity, measured by both the euglycemic-hyperinsulinemic clamp and homeostasis model assessment insulin resistance index (HOMA-IR). Design and Setting: Evaluations were conducted before and 1 month after RYGBP at State University of Campinas (Sao Paulo, Brazil). Patients: Patients included 19 premenopausal women with metabolic syndrome aged 35.3 (6.7) yr, body mass index 45.50 (3.74) kg/m(2) [mean (SD)]. Six had mild type 2 diabetes, seven impaired glucose tolerance, and six normal glucose tolerance. Interventions and Main Outcome Measures: The volunteers underwent RYGBP either alone or combined with omentectomy. Euglycemic-hyperinsulinemic clamp, HOMA-IR, nonesterified fatty acids, leptin, ultrasensitive C-reactive protein, adiponectin, and IL-6 were assessed at baseline and 4.5 (0.9) wk postoperatively. Results: Fasting glucose decreased [99.2 (13.1) to 83.6 (8.1) mg/dl, P < 0.01] along with a reduction in fasting insulin [30.4 (17.0) to 11.4 (6.3) mU/liter, P < 0.01]. M value did not improve postoperatively [25.82 (6.30) to 22.02 (6.05) mu mol/kg(FFM) . min] despite of a decrease in body weight [114.8 (14.5) to 102.3 (14.5) kg, P < 0.001]. This finding was discordant to the observation of an improvement in HOMA-IR [3.85 (2.10) to 1.42 (0.76), P < 0.01]. Nonesterified fatty acids increased. Leptin and C-reactive protein decreased. IL-6 and adiponectin remained unchanged. Conclusions: A month after RYGBP, fasting glucose metabolism improves independent of a change in peripheral insulin sensitivity. (J Clin Endocrinol Metab 95: 3871-3875, 2010) C1 [Lima, Marcelo M. O.; Pareja, Jose C.; Geloneze, Sylka R.; Astiarraga, Brenno D.; Geloneze, Bruno] State Univ Campinas UNICAMP, Lab Invest Metab & Diabet Gastroctr, BR-13081970 Campinas, SP, Brazil. [Pareja, Jose C.; Chaim, Elinton A.] State Univ Campinas UNICAMP, Dept Surg, BR-13081970 Campinas, SP, Brazil. [Alegre, Sarah M.; Astiarraga, Brenno D.] State Univ Campinas UNICAMP, Dept Internal Med, BR-13081970 Campinas, SP, Brazil. [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. RP Lima, MMO (reprint author), State Univ Campinas UNICAMP, Lab Invest Metab & Diabet Gastroctr, 420 Cidade Univ, BR-13081970 Campinas, SP, Brazil. EM endo.marcelolima@hotmail.com RI 5, INCT/H-4505-2013; Diabetes, Inct/I-2186-2013; OI Kahn, Steven/0000-0001-7307-9002 FU Fundacao de Apoio a Pesquisa do Estado de Sao Paulo, Sao Paulo, Brazil [05/58627-2]; U.S. Department of Veterans Affairs FX This work was supported by Fundacao de Apoio a Pesquisa do Estado de Sao Paulo, Sao Paulo, Brazil (Protocol 05/58627-2) and in part by the U.S. Department of Veterans Affairs. This study is registered at www.clinicaltrials.gov (NCT00545805). NR 19 TC 59 Z9 62 U1 0 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2010 VL 95 IS 8 BP 3871 EP 3875 DI 10.1210/jc.2010-0085 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635JW UT WOS:000280652400044 PM 20484482 ER PT J AU Chillambhi, S Turan, S Hwang, DY Chen, HC Juppner, H Bastepe, M AF Chillambhi, Smitha Turan, Serap Hwang, Daw-Yang Chen, Hung-Chun Jueppner, Harald Bastepe, Murat TI Deletion of the Noncoding GNAS Antisense Transcript Causes Pseudohypoparathyroidism Type Ib and Biparental Defects of GNAS Methylation in cis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID XL-ALPHA-S; IMPRINTING CONTROL ELEMENT; G-PROTEIN; AUTOSOMAL-DOMINANT; CONTROL REGION; EPIGENETIC DEFECTS; LOCUS; IDENTIFICATION; CLUSTER; GENE AB Context: GNAS encodes the alpha-subunit of the stimulatory G protein as well as additional imprinted transcripts including the maternally expressed NESP55 and the paternally expressed XL alpha s, antisense, and A/B transcripts. Most patients with pseudohypoparathyroidism type Ib (PHP-Ib) exhibit imprinting defects affecting the maternal GNAS allele, which are thought to reduce/abolish Gs alpha expression in renal proximal tubules and thereby cause resistance to PTH. Objective: Our objective was to define the genetic defect in a previously unreported family with autosomal dominant PHP-Ib. Design and Setting: Analyses of serum and urine chemistries and of genomic DNA and lymphoblastoid-derived RNA were conducted at a tertiary hospital and research laboratory. Patients: Affected individuals presented with muscle weakness and/or paresthesia and showed hypocalcemia, hyperphosphatemia, and elevated serum PTH. Obligate carriers were healthy and revealed no obvious abnormality in mineral ion homeostasis. Results: A novel 4.2-kb microdeletion was discovered in the affected individuals and the obligate carriers, ablating two noncoding GNAS antisense exons while preserving the NESP55 exon. On maternal transmission, the deletion causes loss of all maternal GNAS imprints, partial gain of NESP55 methylation, and PTH resistance. Paternal transmission of the mutation leads to epigenetic alterations in cis, including a partial loss of NESP55 methylation and a partial gain of A/B methylation. Conclusions: The identified deletion points to a unique cis-acting element located telomeric of the NESP55 exon that is critical for imprinting both GNAS alleles. These findings provide novel insights into the molecular mechanisms underlying PHP and GNAS imprinting. (J Clin Endocrinol Metab 95: 3993-4002, 2010) C1 [Chillambhi, Smitha; Turan, Serap; Jueppner, Harald; Bastepe, Murat] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Chillambhi, Smitha; Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Dept Pediat, Boston, MA 02114 USA. [Chillambhi, Smitha; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Turan, Serap] Marmara Univ, Sch Med, Dept Pediat Endocrinol, TR-34722 Istanbul, Turkey. [Hwang, Daw-Yang; Chen, Hung-Chun] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Nephrol, Kaohsiung 80708, Taiwan. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, 50 Blossom St Thier 10, Boston, MA 02114 USA. EM jueppner@helix.mgh.harvard.edu; bastepe@helix.mgh.harvard.edu FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK073911, R37 DK46718]; Scientific and Technical Research Council of Turkey (TUBITAK); Scientific Human Resources Development (BAYG) FX This work was supported by research grants from National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK073911 to M. B. and R37 DK46718 to H.J.). S. T. was the recipient of a fellowship from the Scientific and Technical Research Council of Turkey (TUBITAK), Scientific Human Resources Development (BAYG) within the framework of the Postdoctoral Research Fellowship program. NR 37 TC 60 Z9 62 U1 2 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 AUG PY 2010 VL 95 IS 8 BP 3993 EP 4002 DI 10.1210/jc.2009-2205 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635JW UT WOS:000280652400059 PM 20444925 ER PT J AU Sox, HC Helfand, M Grimshaw, J Dickersin, K Tovey, D Knottnerus, JA Tugwell, P AF Sox, Harold C. Helfand, Mark Grimshaw, Jeremy Dickersin, Kay Tovey, David Knottnerus, J. Andre Tugwell, Peter CA PLoS Med Editors TI Comparative Effectiveness Research: Challenges for Medical Journals SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article C1 [Helfand, Mark] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. [Sox, Harold C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dartmouth Inst, Hanover, NH 03756 USA. [Grimshaw, Jeremy] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Dickersin, Kay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Tovey, David] Cochrane Lib, London, England. [Knottnerus, J. Andre] Univ Maastricht, Dept Gen Practice, Maastricht, Netherlands. [Tugwell, Peter] Univ Ottawa, Dept Med, Ottawa, ON, Canada. [Tugwell, Peter] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. RP Helfand, M (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. EM helfand@ohsu.edu RI Grimshaw, Jeremy/D-8726-2013; Knottnerus, Andre/F-4866-2013; Knottnerus, Johannes/A-3829-2009; OI Grimshaw, Jeremy/0000-0001-8015-8243; Barbour, Virginia/0000-0002-2358-2440; Tugwell, Peter/0000-0001-5062-0556; Clark, Jocalyn/0000-0002-8014-3989 FU Public Library of Science FX Funding: The PLoS Medicine Editors are each paid a salary by the Public Library of Science, and they contributed to this editorial during their salaried time. The other authors received no specific funding for this article. NR 7 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 2010 VL 63 IS 8 BP 862 EP 864 DI 10.1016/j.jclinepi.2010.03.001 PG 3 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 619OQ UT WOS:000279439900010 PM 20434882 ER PT J AU Bloch, MJ Basile, JN AF Bloch, Michael J. Basile, Jan N. TI EXISTING KIDNEY DISEASE CLASSIFICATION GUIDELINE NEEDS TO INCORPORATE DEGREE OF PROTEINURIA WITH ESTIMATED GLOMERULAR FILTRATION RATE TO MORE ACCURATELY PREDICT CARDIOVASCULAR AND RENAL RISK SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Editorial Material C1 [Bloch, Michael J.] St Marys Reg Med Ctr, Risk Reduct Ctr, Reno, NV 89503 USA. [Bloch, Michael J.] Univ Nevada, Sch Med, Dept Med, Reno, NV 89557 USA. [Basile, Jan N.] Med Univ S Carolina, Seinsheimer Cardiovasc Hlth Program, Div Gen Internal Med Geriatr, Charleston, SC 29425 USA. [Basile, Jan N.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Bloch, MJ (reprint author), St Marys Reg Med Ctr, Risk Reduct Ctr, 645 N Arlington St,Suite 460, Reno, NV 89503 USA. EM mbloch@aol.com NR 0 TC 1 Z9 1 U1 0 U2 0 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 AUG PY 2010 VL 12 IS 8 BP 627 EP 630 DI 10.1111/j.1751-7176.2010.00325.x PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 635GX UT WOS:000280644700011 PM 20695941 ER PT J AU Path, ME AF Path, Mary-Elizabeth TI Rehashing endocannabinoid antagonists: can we selectively target the periphery to safely treat obesity and type 2 diabetes? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID CANNABINOID RECEPTOR; SYSTEM; METABOLISM; INSULIN AB A growing body of evidence supports an important role for the endocannabinoid system as a regulator of appetite, body weight, and systemic metabolism, which is overactive in obesity and type 2 diabetes. While initial attempts to target this system using the cannabinoid receptor inverse agonist rimonabant were successful in producing modest weight loss and improving obesity-related metabolic complications in humans, adverse central nervous system side effects precluded introduction of this drug into clinical practice. However, new data, presented by Tam and colleagues in this issue of the JCI, demonstrate that selective blockade of peripheral cannabinoid receptors may be a novel successful therapeutic approach. C1 [Path, Mary-Elizabeth] Joslin Diabet Ctr, Boston, MA 02215 USA. [Path, Mary-Elizabeth] Harvard Univ, Sch Med, Boston, MA USA. RP Path, ME (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu NR 20 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2010 VL 120 IS 8 BP 2646 EP 2648 DI 10.1172/JCI44099 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 633HI UT WOS:000280492100001 ER PT J AU Sun, SH Sprenger, CCT Vessella, RL Haugk, K Soriano, K Mostaghel, EA Page, ST Coleman, IM Nguyen, HM Sun, HY Nelson, PS Plymate, SR AF Sun, Shihua Sprenger, Cynthia C. T. Vessella, Robert L. Haugk, Kathleen Soriano, Kathryn Mostaghel, Elahe A. Page, Stephanie T. Coleman, Ilsa M. Nguyen, Holly M. Sun, Huiying Nelson, Peter S. Plymate, Stephen R. TI Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR-I; TUMOR-CELL LINES; MEDICAL CASTRATION; EPITHELIAL-CELLS; GENE-EXPRESSION; T-ANTIGEN; IGF-IR; PROGRESSION; ACTIVATION; MUTATIONS AB Progression of prostate cancer following castration is associated with increased androgen receptor (AR) expression and signaling despite AR blockade. Recent studies suggest that these activities are due to the generation of constitutively active AR splice variants, but the mechanisms by which these splice variants could mediate such effects are not fully understood. Here we have identified what we believe to be a novel human AR splice variant in which exons 5, 6, and 7 are deleted (AR(v567es)) and demonstrated that this variant can contribute to cancer progression in human prostate cancer xenograft models in mice following castration. We determined that, in human prostate cancer cell lines, AR(v567es) functioned as a constitutively active receptor, increased expression of full-length AR (AR(fl)), and enhanced the transcriptional activity of AR. In human xenografts, human prostate cancer cells transfected with AR(v567es) cDNA formed tumors that were resistant to castration. Furthermore, the ratio of AR(v567es) to AR(fl) expression within the xenografts positively correlated with resistance to castration. Importantly, we also detected AR(v567es) frequently in human prostate cancer metastases. In summary, these data indicate that constitutively active AR splice variants can contribute to the development of castration-resistant prostate cancers and may serve as biomarkers for patients who are likely to suffer from early recurrence and are candidates for therapies directly targeting the AR rather than ligand. C1 [Plymate, Stephen R.] Univ Washington, Sch Med, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. [Vessella, Robert L.; Nguyen, Holly M.; Nelson, Peter S.; Plymate, Stephen R.] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98104 USA. [Vessella, Robert L.; Haugk, Kathleen; Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Mostaghel, Elahe A.; Coleman, Ilsa M.; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. [Sun, Huiying] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Sun, Huiying] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Plymate, SR (reprint author), Univ Washington, Sch Med, Harborview Med Ctr, Dept Med, Box 359625,325 9th Ave, Seattle, WA 98104 USA. EM splymate@u.washington.edu FU NIH-NCI [PO1 CA 85859]; Pacific Northwest Prostate Cancer SPORE [P50 CA 097186]; Veterans Affairs Research Program FX We would like to thank Jennifer Wu and Marco Marcelli for critical review of the manuscript and Martin Escandon for assistance with manuscript preparation. Grants from the NIH-NCI (PO1 CA 85859 to S.R. Plymate, R. Vessella, and P.S. Nelson), the Pacific Northwest Prostate Cancer SPORE (P50 CA 097186 to S.R. Plymate, R. Vessella, and P.S. Nelson), and the Veterans Affairs Research Program (to S.R. Plymate) supported this work. NR 52 TC 302 Z9 310 U1 1 U2 19 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2010 VL 120 IS 8 BP 2715 EP 2730 DI 10.1172/JCI41824 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 633HI UT WOS:000280492100010 PM 20644256 ER PT J AU Cao, HL Yu, SB Yao, Z Galson, DL Jiang, Y Zhang, XY Fan, J Lu, BF Guan, YF Luo, M Lai, YM Zhu, YB Kurihara, N Patrene, K Roodman, GD Xiao, GZ AF Cao, Huiling Yu, Shibing Yao, Zhi Galson, Deborah L. Jiang, Yu Zhang, Xiaoyan Fan, Jie Lu, Binfeng Guan, Youfei Luo, Min Lai, Yumei Zhu, Yibei Kurihara, Noriyoshi Patrene, Kenneth Roodman, G. David Xiao, Guozhi TI Activating transcription factor 4 regulates osteoclast differentiation in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BONE-MINERAL-DENSITY; OSTEOCALCIN GENE-EXPRESSION; MARROW STROMAL CELLS; LACKING C-FOS; PARATHYROID-HORMONE; KEY REGULATOR; T-CELLS; OSTEOBLAST DIFFERENTIATION; RECEPTOR ACTIVATOR; NUCLEAR-FACTOR AB Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Aft4 in mice. OCL differentiation was drastically decreased in Atf4(-/-) bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4(-/-) BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity. C1 [Cao, Huiling; Yu, Shibing; Galson, Deborah L.; Zhang, Xiaoyan; Luo, Min; Kurihara, Noriyoshi; Patrene, Kenneth; Roodman, G. David; Xiao, Guozhi] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Cao, Huiling; Yao, Zhi] Tianjin Med Univ, Educ Minist China, Key Lab, Dept Immunol, Tianjin, Peoples R China. [Jiang, Yu; Lai, Yumei] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Zhang, Xiaoyan; Guan, Youfei] Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing, Peoples R China. [Fan, Jie] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. [Lu, Binfeng; Zhu, Yibei] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA USA. [Xiao, Guozhi] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China. RP Xiao, GZ (reprint author), VA Pittsburgh Healthcare Syst, Rm 2E-107,151-U, Pittsburgh, PA 15240 USA. EM xiaog@upmc.edu RI YU, SHIBING/B-7648-2012; Galson, Deborah/E-9370-2010 OI Galson, Deborah/0000-0002-2045-8807 FU NIH [DK072230, AR057310]; Department of Defense [W81XWH-07-1-0160]; Chinese Ministry of Science and Technology [2009CB918902] FX We thank Renny T. Franceschi (University of Michigan, Ann Arbor, Michigan, USA) for critical reading of this manuscript. Thanks to Harry Blair (University of Pittsburgh, Pittsburgh, Pennsylvania, USA) for expert advice on bone histomorphometry. This work was in part supported by NIH grant DK072230, Department of Defense grant W81XWH-07-1-0160, and Chinese Ministry of Science and Technology grant 2009CB918902 (to G. Xiao) as well as by NIH grant AR057310 (to D.L. Galson). NR 67 TC 32 Z9 33 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 AUG PY 2010 VL 120 IS 8 BP 2755 EP 2766 DI 10.1172/JCI42106 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 633HI UT WOS:000280492100013 PM 20628199 ER PT J AU Liew, CW Bochenski, J Kawamori, D Hu, J Leech, CA Wanic, K Malecki, M Warram, JH Qi, L Krolewski, AS Kulkarni, RN AF Liew, Chong Wee Bochenski, Jacek Kawamori, Dan Hu, Jiang Leech, Colin A. Wanic, Krzysztof Malecki, Maciej Warram, James H. Qi, Ling Krolewski, Andrzej S. Kulkarni, Rohit N. TI The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FUNCTIONAL Q84R POLYMORPHISM; PANCREATIC-ISLETS; TRB3; GLUCOSE; GENE; ACTIVATION; RESISTANCE; EXPRESSION; SECRETION; TRIB3 AB Insufficient insulin secretion and reduced pancreatic beta cell mass are hallmarks of type 2 diabetes (T2DM). Here, we confirm that a previously identified polymorphism (rs2295490/Q84R) in exon 2 of the pseudokinase-encoding gene tribbles 3 (TRB3) is associated with an increased risk for T2DM in 2 populations of people of mixed European descent. Carriers of the 84R allele had substantially reduced plasma levels of C-peptide, the product of proinsulin processing to insulin, suggesting a role for TRB3 in beta cell function. Overexpression of TRB3 84R in mouse beta cells, human islet cells, and the murine beta cell line MIN6 revealed reduced insulin exocytosis, associated with a marked reduction in docked insulin granules visualized by electron microscopy. Conversely, knockdown of TRB3 in MIN6 cells restored insulin secretion and expression of exocytosis genes. Further analysis in MIN6 cells demonstrated that TRB3 interacted with the transcription factor ATF4 and that this complex acted as a competitive inhibitor of cAMP response element-binding (CREB) transcription factor in the regulation of key exocytosis genes. In addition, the 84R TRB3 variant exhibited greater protein stability than wild-type TRB3 and increased binding affinity to Akt. Mice overexpressing TRB3 84R in beta cells displayed decreased beta cell mass, associated with reduced proliferation and enhanced apoptosis rates. These data link a missense polymorphism in human TRB3 to impaired insulin exocytosis and thus increased risk for T2DM. C1 [Liew, Chong Wee; Kawamori, Dan; Hu, Jiang; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Sect Islet Cell & Regenerat Med, Boston, MA USA. [Bochenski, Jacek; Wanic, Krzysztof; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Sect Genet & Epidemiol, Joslin Diabet Ctr,Res Div, Boston, MA USA. [Bochenski, Jacek; Wanic, Krzysztof; Warram, James H.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Leech, Colin A.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY USA. [Wanic, Krzysztof; Malecki, Maciej] Jagiellonian Univ, Sch Med, Dept Metab Disorders, Krakow, Poland. [Qi, Ling] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Qi, Ling] Salk Inst Biol Studies, Labs Peptide Biol, La Jolla, CA 92037 USA. RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Room 602,1 Joslin Pl, Boston, MA 02215 USA. EM Rohit.Kulkarni@joslin.harvard.edu FU NIH [RO1 DK 67536, RO1 DK47475, RO1 TW01351, P30 DK36836, 1RL9EB008539-01]; Graetz Bridge Funds; Manpei Suzuki Diabetes Foundation, Japan; JDRF FX The authors thank M. Montminy and C.R. Kahn for providing reagents and discussions; J. Pessin, G.W. Sharp, and S. Bonner-Weir for advice; L. Huse and E. Morgan for excellent assistance in the preparation of this manuscript; H. Li for assistance with hormone assays; and C. Cahill for assistance with electron microscopy. This work was supported by NIH grant RO1 DK 67536 and the Graetz Bridge Funds (to R.N. Kulkarni), NIH grant RO1 DK47475 (to A.S. Krolewski), NIH grant RO1 TW01351 (to A.S. Krolewski), and the Joslin DERC Specialized Assay and Advanced Microscopy Cores (NIH P30 DK36836). C.W. Liew was supported by a Mary K. Iacocca Postdoctoral Fellowship and an NIH Interdisciplinary training grant (1RL9EB008539-01) (SysCODE). D. Kawamori is the recipient of a research fellowship (Manpei Suzuki Diabetes Foundation, Japan) and a JDRF postdoctoral fellowship. NR 43 TC 64 Z9 67 U1 2 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2010 VL 120 IS 8 BP 2876 EP 2888 DI 10.1172/JCI36849 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 633HI UT WOS:000280492100023 PM 20592469 ER PT J AU DiVall, SA Williams, TR Carver, SE Koch, L Bruning, JC Kahn, CR Wondisford, F Radovick, S Wolfe, A AF DiVall, Sara A. Williams, Tameeka R. Carver, Sarah E. Koch, Linda Bruening, Jens C. Kahn, C. Ronald Wondisford, Fredric Radovick, Sally Wolfe, Andrew TI Divergent roles of growth factors in the GnRH regulation of puberty in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FEMALE REPRODUCTIVE FUNCTION; NEURONAL CELL-LINE; HIGH-FAT DIET; FACTOR-I; GENE-EXPRESSION; BODY-WEIGHT; INSULIN-RECEPTOR; HORMONE NEURONS; SEXUAL-MATURATION; DENDRITIC SPINES AB Pubertal onset, initiated by pulsatile gonadotropin-releasing hormone (GnRH), only occurs in a favorable, anabolic hormonal milieu. Anabolic factors that may signal nutritional status to the hypothalamus include the growth factors insulin and IGF-1. It is unclear which hypothalamic neuronal subpopulation these factors affect to ultimately regulate GnRH neuron function in puberty and reproduction. We examined the direct role of the GnRH neuron in growth factor regulation of reproduction using the Cre/lox system. Mice with the IR or IGF-1R deleted specifically in GnRH neurons were generated. Male and female mice with the IR deleted in GnRH neurons displayed normal pubertal timing and fertility, but male and female mice with the IGF-1R deleted in GnRH neurons experienced delayed pubertal development with normal fertility. With IGF-1 administration, puberty was advanced in control females, but not in females with the IGF-1R deleted in GnRH neurons, in control males, or in knockout males. These mice exhibited developmental differences in GnRH neuronal morphology but normal number and distribution of neurons. These studies define the role of IGF-1R signaling in the coordination of somatic development with reproductive maturation and provide insight into the mechanisms regulating pubertal timing in anabolic states. C1 [DiVall, Sara A.] Johns Hopkins Univ, Div Pediat Endocrinol, Dept Pediat, Baltimore, MD 21212 USA. [Koch, Linda; Bruening, Jens C.] Univ Cologne, Inst Genet, Dept Mouse Genet & Metab, D-5000 Cologne, Germany. [Bruening, Jens C.] Univ Hosp Cologne, Dept Internal Med, Cologne, Germany. [Bruening, Jens C.] Max Planck Inst Biol Aging, Cologne, Germany. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP DiVall, SA (reprint author), Johns Hopkins Univ, Div Pediat Endocrinol, Dept Pediat, 600 N Wolfe St,CMSC 406, Baltimore, MD 21212 USA. EM sdivall1@jhmi.edu OI Koch, Linda/0000-0002-2943-1993 FU Lawson Wilkins Pediatric Endocrine Society (LWPES); NIH [K08HD056139, R01HD044608]; Deutsche Forschungsgemeinschaft (DFG) [Br1492-7]; Eunice Kennedy Shriver NICHD/NIH [U54HD41859] FX The authors thank Brigitte Mann of the Northwestern University Ligand Assay Core Facility for performing the LH radioimmunoassays. We also thank Andrea Gore for helpful advice regarding GnRH and IGF-1R immunofluorescence staining. This work was supported by the Lawson Wilkins Pediatric Endocrine Society (LWPES) Clinical Scholars Award and NIH K08HD056139 to S.A. DiVall, Deutsche Forschungsgemeinschaft (DFG) Br1492-7 to J.C. Bruning, NIH R01HD044608 to A. Wolfe, and the Eunice Kennedy Shriver NICHD/NIH through cooperative agreement U54HD41859 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research. NR 48 TC 60 Z9 63 U1 1 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2010 VL 120 IS 8 BP 2900 EP 2909 DI 10.1172/JCI41069 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 633HI UT WOS:000280492100025 PM 20628204 ER PT J AU Baruch, L Agarwal, S Gupta, B Haynos, A Johnson, S Kelly-Johnson, K Eng, C AF Baruch, Lawrence Agarwal, Sanjay Gupta, Bhanu Haynos, Ann Johnson, Swapna Kelly-Johnson, Katelyn Eng, Calvin TI Is directly measured low-density lipoprotein clinically equivalent to calculated low-density lipoprotein? SO JOURNAL OF CLINICAL LIPIDOLOGY LA English DT Article DE Health policy; Hypercholesterolemia; LDL-C cholesterol; Lipids ID CORONARY-HEART-DISEASE; TREATMENT PANEL-III; CARDIOVASCULAR-DISEASE; POSITION STATEMENT; APOLIPOPROTEIN-B; HIGH-RISK; CHOLESTEROL; EVENTS; RATIOS AB BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) can either be calculated or measured directly. Clinical guidelines recommend the use of calculated LDL-C (C-LDL-C) to guide therapy because the evidence base for cholesterol management is derived almost exclusively from trials that use C-LDL-C, with direct measurement of LDL-C (D-LDL-C) being reserved for those patients who are nonfasting or with significant hypertriglyceridemia. OBJECTIVE: Our aim was to determine the clinical equivalence of directly measured-LDL-C, using a Siemens Advia Chemistry System, and fasting C-LDL-C. METHODS: Eighty-one subjects recruited for two cholesterol treatment studies had at least one C-LDL-C and D-LDL-C performed simultaneously; 64 had a repeat lipid assessment after 4 to 6 weeks of therapy, resulting in 145 pairs of C-LDL-C and D-LDL-C. RESULTS: There was significant correlation between D-LDL-C and C-LDL-C (r(2) = 0.86). Correlation was significantly better in those with lower total cholesterol, triglycerides, and high-density lipoprotein. In 60% of subjects, the difference between D-LDL-C and C-LDL-C was more than 5 mg/dL and greater than 6%. Clinical concordance between D-LDL-C and C-LDL-C was present in 40% of patients, whereas clinical discordance was noted in 25%. One-third had greater than a 15 ing/dL difference between D-LDL-C and C-LDL-C, whereas 25% had a greater than 20 mg/dL difference. In 47% of subjects, the difference between D-LDL-C and C-LDL-C at baseline and follow-up changed by a minimum of 10% or 10 mg/dL. CONCLUSIONS: Our findings suggest that D-LDL-C is not clinically equivalent to C-LDL-C. This puts into question the current recommendation of using D-LDL-C in situations in which C-LDL-C would be inaccurate. Published by Elsevier Inc on behalf of the National Lipid Association. C1 [Baruch, Lawrence; Johnson, Swapna; Kelly-Johnson, Katelyn; Eng, Calvin] James J Peters VA Med Ctr, Med Serv, Bronx, NY 10468 USA. [Baruch, Lawrence; Eng, Calvin] Mt Sinai Sch Med, New York, NY USA. [Agarwal, Sanjay] Valley Hosp, Ridgewood, NJ USA. [Gupta, Bhanu] Mayo Clin, Rochester, MN USA. [Haynos, Ann] Univ Nevada, Reno, NV 89557 USA. RP Baruch, L (reprint author), James J Peters VA Med Ctr, Med Serv, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM lawrence.baruch@va.gov NR 14 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-2874 J9 J CLIN LIPIDOL JI J. Clin. Lipidol. PD AUG PY 2010 VL 4 IS 4 BP 259 EP 264 DI 10.1016/j.jacl.2010.05.003 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 647LB UT WOS:000281618900004 PM 21122658 ER PT J AU Nahed, BV Walcott, BP Ortman, AJ Kahle, KT Aghi, M Peterfreund, RA Coumans, JV AF Nahed, Brian V. Walcott, Brian P. Ortman, Amy J. Kahle, Kristopher T. Aghi, Manish Peterfreund, Robert A. Coumans, Jean-Valery TI Interval, acute onset airway obstruction associated with a fracture of the C4 vertebra in a patient with ankylosing spondylitis SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Editorial Material DE Airway obstruction; Ankylosing spondylitis; Cervical collar; Cervical fracture; Spinal instability ID CERVICAL-SPINE; MOTION; STABILIZATION; COMPLICATIONS; LARYNGOSCOPY; INTUBATION; INJURIES; SURGERY AB We report a 92-year-old female with ankylosing spondylitis who suffered a non-displaced cervical fracture of the C4 vertebral body as the result of a mechanical fall. A rigid cervical collar was used to maintain stability. The patient later went on to develop upper airway obstruction as a result of fracture displacement. She was emergently intubated for airway protection. To our knowledge, this is the first report of interval, acute onset upper airway obstruction caused by cervical instability following trauma and fracture in a patient with ankylosing spondylitis. This example highlights one of the potential complications of rigid cervical collar immobilization in patients with spinal instability. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Nahed, Brian V.; Walcott, Brian P.; Kahle, Kristopher T.; Coumans, Jean-Valery] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Ortman, Amy J.; Peterfreund, Robert A.] Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Aghi, Manish] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. RP Coumans, JV (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St, Boston, MA 02114 USA. EM jcoumans@partners.org NR 15 TC 1 Z9 1 U1 0 U2 0 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 AUG PY 2010 VL 17 IS 8 BP 1085 EP 1088 DI 10.1016/j.jocn.2009.12.010 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 623GK UT WOS:000279726700037 PM 20580996 ER PT J AU Liu, F Williams, RM Liu, HE Chien, NH AF Liu, Fen Williams, Rhonda M. Liu, Hsueh-Erh Chien, Nai-Hui TI The lived experience of persons with lower extremity amputation SO JOURNAL OF CLINICAL NURSING LA English DT Article DE lived experience; lower extremity amputation; nurses; nursing; qualitative research ID LOWER-LIMB AMPUTATION; DIABETIC-PATIENTS; REHABILITATION; ADJUSTMENT; MANAGEMENT; TRAUMA; DEFINITION; AMPUTEES; CARE AB Aim. The aim of this study was to describe and understand the lived experience of people with lower extremity amputation. Background. The loss of a body part can cause physical, psychological and social disturbances. The majority of previous studies in this area focus on the impact of amputation or the effectiveness of rehabilitation programmes. This is the first study in Taiwan exploring the holistic experiences of persons with amputation. Design. A phenomenological research design was used. Methods. Semi-structured interviews were performed with 22 people with lower extremity amputation. Interviews were tape-recorded and transcribed verbatim. Data were analysed using Colaizzi's phenomenological analysis method. Results. The lived experience of persons with lower extremity amputation could be categorised into the following four themes: 'lost in the dark woods', 'emotional collapse', 'difficulty in passing through the shadow' and 'igniting a gleam of hope'. Conclusions. Participants described suffering in physical, psychological and sociocultural realms and the ways they strived to cope with these challenges. The findings of this study provide an enhanced understanding of the experiences of people with lower extremity amputation and underscore the importance of truly listening and responding to their concerns. The need to appreciate cultural context and to develop the peer-based support programme was highlighted. Relevance to clinical practice. Health professionals need to acknowledge the real needs of people with lower extremity amputation and provide them a clear explanation regarding the short-term and long-term health issues associated with amputation during the pre- and post-amputation phase. Health professionals also need to expand the scope of services beyond a physical and prosthetic focus. Supportive psychological and social interventions such as formal support groups and peer support programmes may provide a powerful and inexpensive addition to routine care. Currently, such programmes are unavailable in Taiwan. C1 [Liu, Hsueh-Erh] Chang Gung Univ, Sch Nursing, Tao Yuan, Taiwan. [Liu, Fen] Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Tao Yuan, Taiwan. [Liu, Fen; Chien, Nai-Hui] Chang Gung Inst Technol, Dept Nursing, Tao Yuan, Taiwan. [Williams, Rhonda M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Williams, Rhonda M.] Univ Washington, Seattle, WA 98195 USA. RP Liu, HE (reprint author), Room 33,7F,2nd Med Bldg,259 Wen Haw 1st Rd, Tao Yuan, Taiwan. EM sarah@mail.cgu.edu.tw FU Chang Gung Institute of Technology FX We thank all persons who participated in this study and the prosthetic rehabilitation centres that provided us with access to these participants. Funding for this study was received gratefully from Chang Gung Institute of Technology. NR 45 TC 11 Z9 12 U1 2 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1067 J9 J CLIN NURS JI J. Clin. Nurs. PD AUG PY 2010 VL 19 IS 15-16 BP 2152 EP 2161 DI 10.1111/j.1365-2702.2010.03256.x PG 10 WC Nursing SC Nursing GA 626AI UT WOS:000279937600010 PM 20659195 ER PT J AU Kindler, HL Niedzwiecki, D Hollis, D Sutherland, S Schrag, D Hurwitz, H Innocenti, F Mulcahy, MF O'Reilly, E Wozniak, TF Picus, J Bhargava, P Mayer, RJ Schilsky, RL Goldberg, RM AF Kindler, Hedy Lee Niedzwiecki, Donna Hollis, Donna Sutherland, Susan Schrag, Deborah Hurwitz, Herbert Innocenti, Federico Mulcahy, Mary Frances O'Reilly, Eileen Wozniak, Timothy F. Picus, Joel Bhargava, Pankaj Mayer, Robert J. Schilsky, Richard L. Goldberg, Richard M. TI Gemcitabine Plus Bevacizumab Compared With Gemcitabine Plus Placebo in Patients With Advanced Pancreatic Cancer: Phase III Trial of the Cancer and Leukemia Group B (CALGB 80303) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; COOPERATIVE-ONCOLOGY-GROUP; METASTATIC BREAST-CANCER; CLINICAL-TRIALS; NUDE-MICE; ANGIOGENESIS; COMBINATION; ANTIBODY; TUMOR; MICROENVIRONMENT AB Purpose The combination of gemcitabine plus bevacizumab produced a 21% response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer. These encouraging data led Cancer and Leukemia Group B (CALGB) to conduct a double-blind, placebo-controlled, randomized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients. Patients and Methods Eligible patients had no prior therapy for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, no tumor invasion of adjacent organs, and no increased bleeding risk. The primary end point was overall survival. Patients were stratified by performance status, extent of disease, and prior radiotherapy. Patients received gemcitabine at 1,000 mg/m(2) over 30 minutes on days 1, 8, and 15 every 28 days and bevacizumab at 10 mg/kg or placebo on days 1 and 15 every 28 days. Results Between June 2004 and April 2006, 602 patients were enrolled onto the study and 535 were treated. Median overall survival was 5.8 months for gemcitabine/bevacizumab and 5.9 months for gemcitabine/placebo (P = .95). Median progression-free survival was 3.8 and 2.9 months, respectively (P = .07). Overall response rates were 13% and 10%, respectively. Patients with a performance status of 0, 1, and 2 survived a median of 7.9, 4.8, and 2.4 months, respectively. The only statistically significant differences in grades 3 and 4 toxicity occurred for hypertension (10% v 3%; P < .001) and proteinuria (5% v 1%; P = .002); venous thrombosis grade >= 3 was equivalent in both arms (14% and 15%, respectively). Conclusion The addition of bevacizumab to gemcitabine does not improve survival in advanced pancreatic cancer patients. C1 [Kindler, Hedy Lee] Univ Chicago, Canc Res Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. NW Univ Feinberg, Sch Med, Chicago, IL USA. Duke Univ, Med Ctr, Canc & Leukemia Grp, Stat Ctr B, Durham, NC 27706 USA. Univ N Carolina, Chapel Hill, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Delaware Christiana Care Community Clin Oncol Pro, Wilmington, DE USA. Helen F Graham Canc Ctr, Wilmington, DE USA. Washington Univ, Sch Med, St Louis, MO USA. RP Kindler, HL (reprint author), Univ Chicago, Canc Res Ctr, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM hkindler@medicine.bsd.uchicago.edu RI Goldberg , Richard/M-1311-2013 FU National Cancer Institute to Cancer [CA31946]; Leukemia Group B [80303]; CALGB Statistical Center [CA33601]; Hedy Lee Kindler; Eli Lilly; Genentech; Herbert Hurwitz; Roche; Richard M. Goldberg; [CA41287]; [CA 32291]; [CA47577]; [CA21115]; [CA17145]; [CA77651]; [CA45418]; [CA77440]; [CA47559] FX Supported, in part, by Grants No. CA31946 from the National Cancer Institute to Cancer and Leukemia Group B 80303 (CALGB 80303) trial (R. L. S.), No. CA33601 to the CALGB Statistical Center (S. G.), and No. CA41287, CA 32291, CA47577, CA21115, CA17145, CA77651, CA45418, CA77440, and CA47559.; Stock Ownership: None Honoraria: Herbert Hurwitz, Roche Research Funding: Hedy Lee Kindler, Eli Lilly, Genentech; Herbert Hurwitz, Genentech, Roche; Richard M. Goldberg, Genentech Expert Testimony: None Other Remuneration: Pankaj Bhargava, AVEO Pharmaceuticals NR 37 TC 388 Z9 398 U1 3 U2 19 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2010 VL 28 IS 22 BP 3617 EP 3622 DI 10.1200/JCO.2010.28.1386 PG 6 WC Oncology SC Oncology GA 633GA UT WOS:000280486700013 PM 20606091 ER PT J AU Lin, N Moy, B Come, S Winer, E AF Lin, Nancy Moy, Beverly Come, Steven Winer, Eric TI Dose-Dense Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/neu-Overexpressed/Amplified Breast Cancer Is Not Feasible Because of Excessive Diarrhea (vol 28, pg 2982, 2010) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Correction C1 [Lin, Nancy; Moy, Beverly; Come, Steven; Winer, Eric] Dana Farber Canc Inst, Harvard Canc Ctr, Boston, MA 02115 USA. RP Lin, N (reprint author), Dana Farber Canc Inst, Harvard Canc Ctr, Boston, MA 02115 USA. NR 1 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 AUG 1 PY 2010 VL 28 IS 22 BP 3670 EP 3670 DI 10.1200/JCO.2010.31.3510 PG 1 WC Oncology SC Oncology GA 633GA UT WOS:000280486700021 ER PT J AU Chang, T Fava, M AF Chang, Trina Fava, Maurizio TI The Future of Psychopharmacology of Depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; NICOTINIC ACETYLCHOLINE-RECEPTORS; POSITRON-EMISSION-TOMOGRAPHY; BUPROPION SUSTAINED-RELEASE; SUBSTANCE-P RECEPTORS; MAJOR DEPRESSION; SEXUAL DYSFUNCTION; DOUBLE-BLIND; ANTIDEPRESSANT TREATMENT; VENLAFAXINE-XR AB There are clear limitations to the currently approved pharmacotherapies of depression, including the fact that they are all essentially monoamine-based, have modest efficacy and a relatively slow onset of efficacy, and suffer from significant tolerability issues, particularly in the long term, including sexual dysfunction, weight gain, and cognitive impairments. This article reviews some of the most promising novel mechanisms that are not represented in compounds currently approved for depression in either the United States or Europe and that May represent the future of the psychopharmacologic treatment of depression, potentially addressing some of the efficacy and tolerability issues of antidepressants on the market. These potential antidepressant treatments include the multimodal serotonergic agents, the triple uptake inhibitors, the neurokinin-based novel therapies, the glutamatergic treatments, the nicotinic receptor-based treatments, the neurogenesis-based treatments, and antiglucocorticoid therapies. Some of these mechanisms appear to be more advanced in terms of drug development than others, but they all contribute to the global effort to develop more effective and better tolerated treatments for major depressive disorder. J Clin Psychiatry 2010;71(8):971-975 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Chang, Trina; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. EM MFava@Partners.org FU GlaxoSmithKline; Harvard Medical School; Abbott; Alkermes; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells; Bristol-Myers Squibb; Cephalon; Clinical Trials Solutions; Covidien; Eli Lilly; EnVivo; Forest; Ganeden Biotech; Johnson Johnson; Lichtwer; Lorex; Novartis; Organon; PamLab; Pfizer; Roche; RTC Logic; Sanofi-Aventis; Shire; Solvay; Synthelabo; Wyeth-Ayerst; T-32 Research [MH-19126] FX Dr Chang has received grant/research support from GlaxoSmithKline and Harvard Medical School. Dr Fava has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trials Solutions, Covidien, Eli Lilly, EnVivo, Forest, Ganeden Biotech, GlaxoSmithKline, Johnson & Johnson, Lichtwer, Lorex, Novartis, Organon, PamLab, Pfizer, Roche, RTC Logic, Sanofi-Aventis, Shire, Solvay, Synthelabo, and Wyeth-Ayerst; has been an advisor/consultant for Abbott, Affectis, Amarin, Aspect Medical Systems, AstraZeneca, Auspex, Bayer, Best Practice Project Management, BioMarin, Biovail, BrainCells, Bristol-Myers Squibb, CeNeRx, Cephalon, Clinical Trials Solutions', CNS Response, Compellis, Cypress, Dov, Eisai, Eli Lilly, EPIX, Euthymics Bioscience; Fabre-Kramer, Forest, GenOmind, GlaxoSmithKline, Gruenthal, Janssen, Jazz, Johnson & Johnson, Knoll, Labopharm, Lorex, Lundbeck, MedAvante, Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, PamLab, Pfizer, PharmaStar, Pharmavite, Precision Human Biolaboratory, Prexa, PsychoGenics, Psylin Neurosciences, Rexahn, Ridge Diagnostics, Roche, RCT Logic, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay, Somaxon, Somerset, Synthelabo, Takeda, Tetragenex, TransForm, Transcept, Vanda, and Wyeth-Ayerst; has had speaking/publishing affiliations with Adamed, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir Media Group, Boehringer Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Imedex, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed Elsevier, Novartis, Organon, Pfizer, PharmaStar, United BioSource, and Wyeth-Ayerst; has equity holdings in Compellis; holds a patent for SPCD and has a patent application for a combination of azapirones and bupropion in MDD; and has received copyright royalties for the MGH CPFQ, SFI, ATRQ, DESS, and SAFER.; Dr Chang is supported in part by a T-32 Research Training Grant MH-19126 through the American Psychiatric Association's Program for Minority Research Training in Psychiatry. NR 60 TC 21 Z9 22 U1 1 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2010 VL 71 IS 8 BP 971 EP 975 DI 10.4088/JCP.10m06223blu PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 643KY UT WOS:000281296500001 PM 20797377 ER PT J AU Cizza, G Nguyen, VT Eskandari, F Duan, ZG Wright, EC Reynolds, JC Ahima, RS Blackman, MR AF Cizza, Giovanni Nguyen, Vi T. Eskandari, Farideh Duan, Zhigang Wright, Elizabeth C. Reynolds, James C. Ahima, Rexford S. Blackman, Marc R. CA POWER Study Grp TI Low 24-Hour Adiponectin and High Nocturnal Leptin Concentrations in a Case-Control Study of Community-Dwelling Premenopausal Women With Major Depressive Disorder: The Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression (POWER) Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PLASMA ADIPONECTIN; WEIGHT-LOSS; MARKERS; RISK; ASSOCIATION; PULSATILITY; PREVALENCE; ADIPOKINES; BIOMARKERS; DYNAMICS AB Objective: Major depressive disorder (MDD) is associated with immune system dysfunction and disruption of multiple circadian systems. Adiponectin is an adipo-cytokine with anti-inflammatory and antiatherogenic effects: Circulating concentrations are inversely related to adiposity and risks of metabolic syndrome and diabetes mellitus. Our goals were (1) to establish whether premenopausal women with MDD exhibit decreased plasma adiponectin concentrations and/or disruption of circadian adiponectin rhythmicity; (2) to assess whether there is a relationship between adiponectin and MDD; and (3) to explore the temporal relationships among adiponectin, leptin, corticotropin, and cortisol secretion. Method: We conducted a case-control study of community-dwelling premenopausal women with DSM-IV MDD (n=23) and age- and body mass index (BMI)-matched control subjects (n=23). Main outcome measures were circulating concentrations of adiponectin, leptin, corticotropin, and cortisol measured hourly for 24 hours. Subjects were recruited from July 1, 2001, to February 28, 2003. Results: Women with MDD had approximately 30% lower mean 24-hour concentration of adiponectin than did control subjects. Adiponectin concentration was inversely related to depression severity and total duration of disease, suggesting a causal link. In contrast, mean nocturnal leptin concentration was higher in the MDD versus control groups. Mean leptin concentration was inversely related to cortisol and adiponectin concentrations, both in subjects with depression and in control subjects. In cross-correlation analyses, the relationship between corticotropin and cortisol concentrations was stronger in women with MDD than in control subjects, a finding consistent with hypothalamic-pituitary-adrenal (HPA) axis activation in MDD. Conclusions: In premenopausal women with MDD, reduced daily adiponectin production may increase the risk of diabetes mellitus, and elevated leptin may contribute to osteoporosis. J Clin Psychiatry 2010;71(8):1079-1087 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Cizza, Giovanni] NIDDK, Clin Endocrine Sect, Clin Endocrinol Branch, NIH,CRC, Bethesda, MD 20892 USA. [Nguyen, Vi T.] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Eskandari, Farideh] NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA. [Duan, Zhigang; Wright, Elizabeth C.] NIDDK, Off Director, Bethesda, MD 20892 USA. [Reynolds, James C.] NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Ahima, Rexford S.] Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Blackman, Marc R.] NIH, Endocrine Sect, NCCAM, Bethesda, MD 20892 USA. [Blackman, Marc R.] Vet Affairs Med Ctr, Res Serv, Washington, DC 20422 USA. RP Cizza, G (reprint author), NIDDK, Clin Endocrine Sect, Clin Endocrinol Branch, NIH,CRC, Bldg 10,Rm 6-3940, Bethesda, MD 20892 USA. EM cizzag@intra.niddk.nih.gov FU NIMH; NIDDK; NCCAM, NIH, Bethesda, Maryland FX The study was fully supported by the Intramural Research Programs of the NIMH; NIDDK; and NCCAM, NIH, Bethesda, Maryland. NR 45 TC 36 Z9 40 U1 0 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2010 VL 71 IS 8 BP 1079 EP 1087 DI 10.4088/JCP.09m05314blu PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 643KY UT WOS:000281296500016 PM 20492842 ER PT J AU Fang, YR Yuan, CM Xu, YF Chen, J Wu, ZG Cao, L Yi, ZH Hong, W Wang, Y Jiang, KD Gao, KM Cui, XJ Nierenberg, AA AF Fang, Yiru Yuan, Chengmei Xu, Yifeng Chen, Jun Wu, Zhiguo Cao, Lan Yi, Zhenghui Hong, Wu Wang, Yong Jiang, Kaida Gao, Keming Cui, Xingjia Nierenberg, Andrew A. CA OPERATION Study Team TI Comparisons of the Efficacy and Tolerability of Extended-Release Venlafaxine, Mirtazapine, and Paroxetine in Treatment-Resistant Depression A Double-Blind, Randomized Pilot Study in a Chinese Population SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE treatment-resistant depression; switch strategies; extended-release venlafaxine; mirtazapine; paroxetine ID STAR-ASTERISK-D; SEROTONIN REUPTAKE INHIBITORS; SWITCHING ANTIDEPRESSANTS; REMISSION RATES; DISORDER; TRIAL; ALTERNATIVES; OUTPATIENTS; DEFINITION; FLUOXETINE AB To compare the efficacy and tolerability of antidepressants switch with extended-release venlafaxine (venlafaxine-XR), mirtazapine, and paroxetine in Chinese patients with major depressive disorder who had 2 consecutive unsuccessful antidepressant trials. One hundred fifty adult patients with treatment-resistant depression according to their medical records and/or response to current treatments were randomly assigned to receive fixed-dosage treatment of venlafaxine-XR 225 mg/d (n = 50), mirtazapine 45 mg/d (n = 55), or paroxetine 20 mg/d (n = 45) for 8 weeks. The primary outcome was the remission rates that were defined as a score 7 or lower on the 17-item Hamilton Rating Scale for Depression (HRSD-17). Secondary outcomes included the remission rate defined by the Self-Rating Depression Scale of 50 or lower and the response rate defined by a 50% reduction or greater on the HRSD-17 total score, and the improvement of patients' general health functions. The completion rates were 82% for venlafaxine-XR, 81.8% for mirtazapine, and 82.2% for paroxetine. Only one patient in paroxetine arm discontinued the study owing to an adverse event. The remission rates based on the HRSD-17 were 42.0% for venlafaxine-XR, 36.4% for mirtazapine, and 46.7% for paroxetine. There were no statistical significances between treatment arms in remission rates. Similarly, there were also no significant differences between groups in secondary outcome measure. Venlafaxine-XR, mirtazapine, and paroxetine were equally effective in the treatment of Chinese patients with major depressive disorder who failed at least 2 previous antidepressant treatments. Selecting any of these 3 antidepressants as a third-step antidepressant is a reasonable choice for this group of patients. C1 [Fang, Yiru] Shanghai Jiao Tong Univ, Sch Med, Dept Psychiat, Div Mood Disorder,Shanghai Mental Hlth Ctr, Shanghai 200030, Peoples R China. [Gao, Keming] Case Western Reserve Univ, Sch Med, Dept Psychiat,Mood & Anxiety Clin, Mood Disorders Program,Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Cui, Xingjia] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [Cui, Xingjia] Canandaigua VA Med Ctr, Rochester, NY USA. [Nierenberg, Andrew A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Fang, YR (reprint author), Shanghai Jiao Tong Univ, Sch Med, Dept Psychiat, Div Mood Disorder,Shanghai Mental Hlth Ctr, 600 S Wan Ping Rd, Shanghai 200030, Peoples R China. EM yirufang@yahoo.com.cn FU Ministry of Science and Technology of China [2004BA720A21-02, 2006AA02Z430]; Science and Technology Commission of Shanghai Municipality [064119533]; AstraZeneca; National Alliance for Research on Schizophrenia and Depression; Pfizer; Bristol-Myers Squibb; Cederroth; Cyberonics; Eli Lilly; Forest Pharmaceuticals; GlaxoSmithKline; Janssen Pharmaceutica; Lichtwer Pharma; National Institute of Mental Health; Organon; Stanley Foundation; Wyeth-Ayerst Laboratories FX This work was supported by the "10th Five-year Plan"of National Key Technologies R&D Program grants 2004BA720A21-02 (Ministry of Science and Technology of China) and the "Climbing Mountain Action Plan" Program grants 064119533 (Science and Technology Commission of Shanghai Municipality) and partly supported by National High-tech R&D Program (863 Program) grants 2006AA02Z430 (Ministry of Science and Technology of China).; Dr Gao received grant support from AstraZeneca and National Alliance for Research on Schizophrenia and Depression and was on an advisory board of Schering-Plough and a speaker's bureau of Pfizer.; Dr Nierenberg has provided scientific consultation for Bristol-Myers Squibb, Janssen Pharmaceutica, Eli Lilly, Genaissance, GlaxoSmithKline, Innapharma, Neuronetics, Pfizer, Sepracor, and Shire and has received research support from Bristol-Myers Squibb, Cederroth, Cyberonics, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Lichtwer Pharma, National Alliance for Research on Schizophrenia and Depression, National Institute of Mental Health, Organon, Pfizer, Stanley Foundation, and Wyeth-Ayerst Laboratories. Dr Nierenberg has also received honoraria from Cyberonics, Eli Lilly, GlaxoSmithKline, and Wyeth-Ayerst Laboratories. NR 41 TC 27 Z9 33 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2010 VL 30 IS 4 BP 357 EP 364 DI 10.1097/JCP.0b013e3181e7784f PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 625MY UT WOS:000279900700002 PM 20571433 ER PT J AU Myrick, H Li, XB Randall, PK Henderson, S Voronin, K Anton, RF AF Myrick, Hugh Li, Xingbao Randall, Patrick K. Henderson, Scott Voronin, Konstantin Anton, Raymond F. TI The Effect of Aripiprazole on Cue-Induced Brain Activation and Drinking Parameters in Alcoholics SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE neuroimaging; alcoholism; craving; aripiprazole ID RAT NUCLEUS-ACCUMBENS; CLINICAL LABORATORY PARADIGM; EXTRACELLULAR DOPAMINE; VENTRAL STRIATUM; ANTIPSYCHOTIC-DRUG; DOUBLE-BLIND; RECEPTOR AVAILABILITY; RELAPSE PREVENTION; DEPENDENT SUBJECTS; PARTIAL AGONIST AB Because the effects of alcohol and its environmental cues on brain dopamine have been implicated in the maintenance of heavy drinking, drugs that modify dopamine might be useful in reducing drinking or promoting abstinence. The goal of the current study was to use an established brain imaging paradigm to explore the effect of aripiprazole (final dose 15 mg over a 14-day period), a dopamine stabilizer medication, on alcohol cue-induced brain activation and drinking in alcoholics. Non-treatment-seeking alcoholics were randomly assigned aripiprazole (n = 14) or identical placebo (n = 16) and reported their alcohol use while taking study medication for 14 days before an alcohol cue-induced brain functional magnetic resonance imaging study. In a Philips 3.0-T magnetic resonance imaging scanner, subjects were given a sip of alcohol before viewing a randomized presentation alcoholic-and nonalcoholic-beverage photographs while subjects rated their urge to drink. During photograph presentation, changes in regional brain activity were measured, and differences between viewing alcoholic beverage and nonalcoholic beverages were compared within and between groups. Brain activity analysis revealed increased activation for placebo-treated subjects in the right ventral striatum (P < 0.005; threshold 15 voxels), while there was a blunting of activation in this area in the aripiprazole-treated subjects. Aripiprazole-treated subjects, compared with placebo-treated subjects, also had significantly less heavy drinking during the 14-day medication period. The study provides both novel and valuable information regarding the effect of aripiprazole on cue-induced brain activation and voluntary drinking during treatment. C1 [Myrick, Hugh; Henderson, Scott] Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Res & Dev Serv, Charleston, SC 29425 USA. [Myrick, Hugh; Li, Xingbao; Randall, Patrick K.; Henderson, Scott; Voronin, Konstantin; Anton, Raymond F.] Med Univ S Carolina, Alcohol Res Ctr, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Myrick, Hugh; Li, Xingbao] Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. RP Myrick, H (reprint author), Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Res & Dev Serv, IOP 4N,67 President St,MSC 861, Charleston, SC 29425 USA. EM myrickh@musc.edu FU Charleston Alcohol Research Center [NIAAA P50 AA10761]; NIAAA [K23 AA00314]; VA Research and Development Service, Ralph H. Johnson Department of Veterans Affairs Medical Center; Bristol-Myers Squibb FX This work was funded by the Charleston Alcohol Research Center (NIAAA P50 AA10761). Dr Myrick is also funded through NIAAA K23 AA00314 and the VA Research and Development Service, Ralph H. Johnson Department of Veterans Affairs Medical Center.; Drs Anton and Myrick have received grant support from Bristol-Myers Squibb. Dr Myrick is a member of the Bristol-Myers Squibb speakers' bureau, and Dr Anton has been a consultant for Bristol-Myers Squibb. Drs Voronin, Li, and Randall and Mr Henderson reported no biomedical financial interests or potential conflicts of interest. NR 72 TC 28 Z9 29 U1 5 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2010 VL 30 IS 4 BP 365 EP 372 DI 10.1097/JCP.0b013e3181e75cff PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 625MY UT WOS:000279900700004 PM 20571434 ER PT J AU Schutt, RK Schapira, L Maniates, J Santiccioli, J Henlon, S Bigby, J AF Schutt, Russell K. Schapira, Lidia Maniates, Jennifer Santiccioli, Jessica Henlon, Silas Bigby, JudyAnn TI Community Health Workers' Support for Cancer Clinical Trials: Description and Explanation SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Community health workers; Cancer clinical trials; Medical research; Community attitudes; Health care disparities ID AGE-BASED DISPARITIES; MEDICAL-RESEARCH; AFRICAN-AMERICANS; PARTICIPATION; CARE; RECRUITMENT; ATTITUDES; WOMEN AB Ethnic differences in participation in cancer clinical trials slow advances in medical knowledge that can reduce health care disparities. Community health workers (CHWs) are an increasingly important bridge between the health care system and underserved communities and could play an important role in increasing rates of clinical trial participation. We investigated community health workers' orientations to medical research and cancer clinical trials with a mixed methods design: two focus groups, 11 intensive interviews, and a structured survey of 76 CHW training workshop participants. CHWs demonstrated high levels of commitment to improving the health of community members but considerable distrust of researchers' motives, low levels of knowledge about cancer clinical trials, and frequent perceptions of bias in the health care system. Support for research is associated with more research experience, self-assessed knowledge, and Hispanic ethnicity, but with less seniority as a CHW. Neither actual knowledge of cancer clinical trials nor perceptions of bias in the health care system were related to degree of support for medical research. Community health workers perceive bias in the health care system but recognize the importance of medical research and are interested in learning more about cancer clinical trials. Research experience increases support for medical research; education increases perceptions of health care system bias. C1 [Schutt, Russell K.] Univ Massachusetts, Dept Sociol, Boston, MA 02125 USA. [Schapira, Lidia] Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Breast Canc, Boston, MA 02114 USA. [Maniates, Jennifer] Execut Off Hlth & Human Serv, Off Behav Hlth MassHlth, Boston, MA 02111 USA. [Santiccioli, Jessica] Business Knowledge Serv, Holliston, MA 01746 USA. [Bigby, JudyAnn] Commonwealth Massachusetts, Execut Off Hlth & Human Serv, Boston, MA 02108 USA. RP Schutt, RK (reprint author), Univ Massachusetts, Dept Sociol, 100 Morrissey Blvd, Boston, MA 02125 USA. EM russell.schutt@umb.edu NR 36 TC 3 Z9 3 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD AUG PY 2010 VL 35 IS 4 BP 417 EP 422 DI 10.1007/s10900-010-9267-0 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 642TB UT WOS:000281239700010 PM 20352478 ER PT J AU Harrington, EF Crowther, JH Shipherd, JC AF Harrington, Ellen F. Crowther, Janis H. Shipherd, Jillian C. TI Trauma, Binge Eating, and the "Strong Black Woman" SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE trauma; binge eating; Strong Black Woman; sociocultural factors ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL EXPERIENCES SURVEY; NATURAL-ENVIRONMENT; DIAGNOSTIC SCALE; BULIMIA-NERVOSA; AMERICAN WOMEN; RISK-FACTORS; SELF; ABUSE; VALIDATION AB Objective: The primary goal of this study was to test a culturally specific model of binge eating in African American female trauma survivors, investigating potential mechanisms through which trauma exposure and distress were related to binge eating symptomatology. Method: Participants were 179 African American female trauma survivors who completed questionnaires about traumatic experiences; emotional inhibition/regulation difficulties; self-silencing (prioritizing others' needs and adopting external self-evaluation standards); eating for psychological reasons; binge eating; and internalization of "Strong Black Woman" (SBW) ideology, an important cultural symbol emphasizing strength and self-sufficiency. Results: Structural path analysis supported the proposed model in which SBW ideology, emotional inhibition/regulation difficulties, and eating for psychological reasons mediated the relationship between trauma exposure/distress and binge eating. The proposed model provided better fit to the data than several competing models. Conclusions: These findings suggest that among African American trauma survivors, trauma exposure and distress predict greater internalization of SBW ideology, which is associated with emotional inhibition/regulation difficulties, eating for psychological reasons, and ultimately binge eating. Implications of these findings for assessment, treatment, and prevention efforts are discussed. C1 [Harrington, Ellen F.; Shipherd, Jillian C.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Harrington, Ellen F.; Crowther, Janis H.] Kent State Univ, Dept Psychol, Kent, OH 44242 USA. [Shipherd, Jillian C.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Harrington, EF (reprint author), St Thomas Hosp, Summa Hlth Syst, Ctr Treatment & Study Traumat Stress, 4th Floor Ambulatory Bldg, Akron, OH 44310 USA. EM harringtone@summa-health.org NR 59 TC 29 Z9 29 U1 1 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2010 VL 78 IS 4 BP 469 EP 479 DI 10.1037/a0019174 PG 11 WC Psychology, Clinical SC Psychology GA 637MV UT WOS:000280823100003 PM 20658804 ER PT J AU Lester, K Resick, PA Young-Xu, Y Artz, C AF Lester, Kristin Resick, Patricia A. Young-Xu, Yinong Artz, Caroline TI Impact of Race on Early Treatment Termination and Outcomes in Posttraumatic Stress Disorder Treatment SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE African Americans; posttraumatic stress disorder; cognitive processing therapy; prolonged exposure; dropout ID COGNITIVE-PROCESSING THERAPY; ADMINISTERED PTSD SCALE; BEHAVIORAL THERAPY; AFRICAN-AMERICAN; RAPE VICTIMS; SELF-REPORT; PSYCHOTHERAPY; AGORAPHOBIA; PREVALENCE; SERVICES AB Objective: The present study investigated the influence of race on posttraumatic stress disorder (PTSD) treatment among 94 African American and 214 Caucasian female victims of interpersonal violence participating in 2 studies of cognitive behavioral treatment for PTSD that were conducted sequentially and continuously. Method: In each study, participants were randomized into 1 of 3 conditions. The first study compared cognitive processing therapy with prolonged exposure and a delayed treatment condition. In the second study, cognitive processing therapy was compared with its constituent components: cognitive therapy only and written accounts. Participants were assessed with the Clinician Administered PTSD Scale and the Structured Clinical Interview for DSM-IV, as well as through self-report measures of PTSD. Results: Analyses revealed that African Americans were significantly less likely to complete treatment compared with Caucasians (45% vs. 73%, respectively, p < .001) and that the differences held even after controlling for education and income. Despite racial differences in treatment completion status, analyses with the intent-to-treat sample indicated no racial differences in outcomes on PTSD measures. Conclusions: The lack of difference in treatment outcomes despite racial differences in dropout may be explained by greater symptom improvement of African Americans who dropped out compared with Caucasians who dropped out. Implications of these findings and practical approaches to addressing sociocultural barriers to care are explored. C1 [Lester, Kristin; Resick, Patricia A.; Artz, Caroline] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Resick, Patricia A.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Resick, Patricia A.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Young-Xu, Yinong] Vet Affairs Med Ctr, Natl Ctr PTSD, Execut Div, White River Jct, VT USA. RP Lester, K (reprint author), Dept Vet Affairs Tuscaloosa, 116-PSY,3701 Loop Rd, Tuscaloosa, AL 35404 USA. EM kristin.lester@va.gov NR 39 TC 31 Z9 31 U1 3 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2010 VL 78 IS 4 BP 480 EP 489 DI 10.1037/a0019551 PG 10 WC Psychology, Clinical SC Psychology GA 637MV UT WOS:000280823100004 PM 20658805 ER PT J AU Hirshfeld-Becker, DR Masek, B Henin, A Blakely, LR Pollock-Wurman, RA McQuade, J DePetrillo, L Briesch, J Endick, TH Rosenbaum, JF Biederman, J AF Hirshfeld-Becker, Dina R. Masek, Bruce Henin, Aude Blakely, Lauren Raezer Pollock-Wurman, Rachel A. McQuade, Julia DePetrillo, Lillian Briesch, Jacquelyn Endick, Thomas H. Rosenbaum, Jerrold F. Biederman, Joseph TI Cognitive Behavioral Therapy for 4-to 7-Year-Old Children With Anxiety Disorders: A Randomized Clinical Trial SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE childhood anxiety disorders; cognitive behavioral therapy; preschoolers; behavioral inhibition; randomized clinical trial ID PRESCHOOL-CHILDREN; FOLLOW-UP; PSYCHIATRIC-DISORDERS; PSYCHOSOCIAL IMPAIRMENT; EARLY INTERVENTION; CHILDHOOD ANXIETY; REFERRED CHILDREN; ANXIOUS CHILDREN; SOCIAL ANXIETY; PANIC DISORDER AB Objective: To examine the efficacy of a developmentally appropriate parent child cognitive behavioral therapy (CBI) protocol for anxiety disorders in children ages 4-7 years. Method: Design: Randomized wait-list controlled trial. Conduct: Sixty-four children (53% female, mean age 5.4 years, 80% European American) with anxiety disorders were randomized to a parent child CBT intervention (n = 34) or a 6-month wait-list condition (n = 30). Children were assessed by interviewers blind to treatment assignment, using structured diagnostic interviews with parents, laboratory assessments of behavioral inhibition, and parent questionnaires. Analysis: Chi-square analyses of outcome rates and linear and ordinal regression of repeated measures, examining time by intervention interactions. Results: The response rate (much or very much improved on the Clinical Global Impression Scale for Anxiety) among 57 completers was 69% versus 32% (CBT vs. controls), p < .01; intent-to-treat: 59% vs. 30%, p = .016. Treated children showed a significantly greater decrease in anxiety disorders (effect size [ES] = .55) and increase in parent-rated coping (ES = .69) than controls, as well as significantly better CGI improvement on social phobia/avoidant disorder (ES = .95), separation anxiety disorder (ES = .82), and specific phobia (ES = .78), but not on generalized anxiety disorder. Results on the Child Behavior Checklist Internalizing scale were not significant and were limited by low return rates. Treatment response was unrelated to age or parental anxiety but was negatively predicted by behavioral inhibition. Gains were maintained at 1-year follow-up. Conclusions: Results suggest that developmentally modified parent child CBT may show promise in 4- to 7-year-old children. C1 [Hirshfeld-Becker, Dina R.; Masek, Bruce; Henin, Aude; Blakely, Lauren Raezer; Pollock-Wurman, Rachel A.; McQuade, Julia; DePetrillo, Lillian; Briesch, Jacquelyn; Rosenbaum, Jerrold F.; Biederman, Joseph] Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Hirshfeld-Becker, Dina R.; Masek, Bruce; Henin, Aude; Pollock-Wurman, Rachel A.; Rosenbaum, Jerrold F.; Biederman, Joseph] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Endick, Thomas H.] Virginia Polytech Inst & State Univ, Dept Psychol, Blacksburg, VA 24061 USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Alewife Brook Pkway,Suite 2000, Cambridge, MA 02138 USA. EM dhirshfeld@partners.org OI McQuade, Julia/0000-0001-9278-3345 FU NIMH NIH HHS [K08 MH001538] NR 63 TC 79 Z9 80 U1 2 U2 33 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2010 VL 78 IS 4 BP 498 EP 510 DI 10.1037/a0019055 PG 13 WC Psychology, Clinical SC Psychology GA 637MV UT WOS:000280823100006 PM 20658807 ER PT J AU Holmbeck, GN DeLucia, C Essner, B Kelly, L Zebracki, K Friedman, D Jandasek, B AF Holmbeck, Grayson N. DeLucia, Christian Essner, Bonnie Kelly, Lauren Zebracki, Kathy Friedman, Deborah Jandasek, Barbara TI Trajectories of Psychosocial Adjustment in Adolescents With Spina Bifida: A 6-Year, Four-Wave Longitudinal Follow-Up SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE spina bifida; psychosocial adjustment; growth analyses; adolescence ID EXECUTIVE FUNCTIONS; FAMILIES; CHILDREN; PERSPECTIVE; MULTIMETHOD; PSYCHOLOGY; TRANSITION; ATTENTION; CONFLICT; ILLNESS AB Objective: As a follow-up to an earlier cross-sectional study (Holmbeck et al., 2003), the current multimethod, multi-informant investigation examined individual growth in psychosocial adjustment across the adolescent transition in 2 samples: young adolescents with spina bifida (SB) and typically developing adolescents (N = 68 in both groups at Time 1). Method: Growth curve modeling procedures were used to describe the developmental course of psychosocial adjustment across 4 waves of data collection from ages 8 to 15. Child gender was included in the models as a moderator of associations between illness status and adjustment trajectories. Results and Conclusions: Findings revealed that preadolescent differences between groups were maintained for several adjustment variables, indicating that adolescents with SB have enduring academic and attention problems and difficulties with social development (e.g., fewer friends and less influence during family interactions). For other outcomes, trajectories of adjustment levels for adolescents with SB converged on levels observed in comparison adolescents, indicating some areas of resilience. Girls with SB were at risk for increasing levels of social difficulties and negative perceptions of their physical appearance. Clinical implications are discussed. C1 [Holmbeck, Grayson N.; Essner, Bonnie; Kelly, Lauren] Loyola Univ, Dept Psychol, Chicago, IL 60626 USA. [DeLucia, Christian] Nova SE Univ, Ctr Psychol Studies, Ft Lauderdale, FL 33314 USA. [Zebracki, Kathy] Shriners Hosp Children, Dept Psychol, Chicago, IL USA. [Friedman, Deborah] Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Boston, MA 02114 USA. [Jandasek, Barbara] Bradley Hasbro Childrens Res Ctr, Dept Child & Adolescent Psychiat, Providence, RI USA. RP Holmbeck, GN (reprint author), Loyola Univ, Dept Psychol, 6525 N Sheridan Rd, Chicago, IL 60626 USA. EM gholmbe@luc.edu FU NICHD NIH HHS [R01 HD048629] NR 48 TC 24 Z9 24 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2010 VL 78 IS 4 BP 511 EP 525 DI 10.1037/a0019599 PG 15 WC Psychology, Clinical SC Psychology GA 637MV UT WOS:000280823100007 PM 20658808 ER PT J AU Mueser, KT Pratt, SI Bartels, SJ Swain, K Forester, B Cather, C Feldman, J AF Mueser, Kim T. Pratt, Sarah I. Bartels, Stephen J. Swain, Karin Forester, Brent Cather, Corinne Feldman, James TI Randomized Trial of Social Rehabilitation and Integrated Health Care for Older People With Severe Mental Illness SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE severe mental illness; social skills training; psychiatric rehabilitation; aging; health management ID LIVING SKILLS; PSYCHOSOCIAL INTERVENTION; SCHIZOPHRENIA-PATIENTS; CONSENSUS STATEMENT; PSYCHOTIC DISORDERS; NEGATIVE SYMPTOMS; SELF-EFFICACY; COMMUNITY; BEHAVIOR; GENDER AB Objective: The Helping Older People Experience Success (HOPES) program was developed to improve psychosocial functioning and reduce long-term medical burden in older people with severe mental illness (SMI) living in the community. HOPES includes 1 year of intensive skills training and health management, followed by a 1-year maintenance phase. Method: To evaluate effects of HOPES on social skills and psychosocial functioning, we conducted a randomized controlled trial with 183 older adults with SMI (58% schizophrenia spectrum) age 50 and older at 3 sites who were assigned to HOPES or treatment as usual with blinded follow-up assessments at baseline and 1- and 2-year follow-up. Results: Retention in the HOPES program was high (80%). Intent-to-treat analyses showed significant improvements for older adults assigned to HOPES compared to treatment as usual in performance measures of social skill, psychosocial and community functioning, negative symptoms, and self-efficacy, with effect sizes in the moderate (.37-.63) range. Exploratory analyses indicated that men improved more than women in the HOPES program, whereas benefit from the program was not related to psychiatric diagnosis, age, or baseline levels of cognitive functioning, psychosocial functioning, or social skill. Conclusions: The results support the feasibility of engaging older adults with SMI in the HOPES program, an intensive psychiatric rehabilitation intervention that incorporates skills training and medical case management, and improves psychosocial functioning in this population. Further research is needed to better understand gender differences in benefit from the HOPES program. C1 [Mueser, Kim T.; Pratt, Sarah I.; Swain, Karin] Dartmouth Psychiat Res Ctr, Concord, NH 03301 USA. [Mueser, Kim T.; Pratt, Sarah I.; Swain, Karin] Dartmouth Med Sch, Dept Psychiat, Concord, NH USA. [Mueser, Kim T.; Pratt, Sarah I.; Bartels, Stephen J.; Swain, Karin] Dartmouth Med Sch, Dept Community & Family Med, Concord, NH USA. [Bartels, Stephen J.] Dartmouth Inst Hlth Care Policy & Clin Practice, Ctr Aging Res, Hanover, NH USA. [Forester, Brent; Cather, Corinne; Feldman, James] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Forester, Brent] McLean Hosp, Boston, MA USA. [Cather, Corinne] Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. [Feldman, James] Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Mueser, KT (reprint author), Dartmouth Psychiat Res Ctr, Main Bldg,105 Pleasant St, Concord, NH 03301 USA. EM kim.t.mueser@dartmouth.edu FU NIMH NIH HHS [R01 MH062324, K23 MH080021, K23 MH080021-01A1, K23 MH080021-02, K23 MH080021-03, R01 MH062324-01A1, R01 MH62324] NR 62 TC 32 Z9 32 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2010 VL 78 IS 4 BP 561 EP 573 DI 10.1037/a0019629 PG 13 WC Psychology, Clinical SC Psychology GA 637MV UT WOS:000280823100011 PM 20658812 ER PT J AU Cao, H Wang, J Li, X Florez, S Huang, Z Venugopalan, SR Elangovan, S Skobe, Z Margolis, HC Martin, JF Amendt, BA AF Cao, H. Wang, J. Li, X. Florez, S. Huang, Z. Venugopalan, S. R. Elangovan, S. Skobe, Z. Margolis, H. C. Martin, J. F. Amendt, B. A. TI MicroRNAs Play a Critical Role in Tooth Development SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE Dicer1; dental stem cells; craniofacial and tooth microRNAs; epithelial differentiation ID STEM-CELLS; AMELOGENESIS IMPERFECTA; DENTAL EPITHELIUM; MOUSE DEVELOPMENT; DIFFERENTIATION; AMELOBLASTIN; PITX2; DICER AB MicroRNAs are known to regulate gene function in many tissues and organs, but their expression and function, if any, in tooth development are elusive. We sought to identify them by microRNA screening analyses and reveal their overall roles by inactivating Dicer1 in the dental epithelium and mesenchyme. Discrete sets of microRNAs are expressed in molars compared with incisors as well as epithelium compared with mesenchyme. Conditional knockout (cKO) of Dicer1 (mature microRNAs) in the dental epithelium of the Pitx2-Cre mouse results in multiple and branched enamel-free incisors and cuspless molars, and change in incisor patterning and in incisor and molar size and shape. Analyses of differentiating dental epithelial markers reveal a defect in ameloblast differentiation. Conversely, the cervical loop (stem cell niche) is expanded in Dicer1 cKO. These results demonstrate that tooth development is tightly controlled by microRNAs and that specific microRNAs regulate tooth epithelial stem cell differentiation. C1 [Cao, H.; Wang, J.; Li, X.; Florez, S.; Huang, Z.; Venugopalan, S. R.; Martin, J. F.; Amendt, B. A.] Texas A&M Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX 77030 USA. [Elangovan, S.; Skobe, Z.; Margolis, H. C.] Forsyth Inst, Dept Biomineralizat, Boston, MA USA. RP Amendt, BA (reprint author), Texas A&M Hlth Sci Ctr, Inst Biosci & Technol, 2121 W Holcombe Blvd, Houston, TX 77030 USA. EM bamendt@ibt.tamhsc.edu FU National Institute of Dental and Craniofacial Research [DE 13941] FX We thank Drs. Tord A. Hjalt (University of Lund, Sweden) and Robert Schwartz (TAMHSC-IBT) for reagents and technical advice, and members of the Amendt laboratory for helpful discussions. Support for this research was provided from grant DE 13941 from the National Institute of Dental and Craniofacial Research to Brad A. Amendt. NR 25 TC 49 Z9 49 U1 1 U2 9 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 AUG PY 2010 VL 89 IS 8 BP 779 EP 784 DI 10.1177/0022034510369304 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 629JY UT WOS:000280194800004 PM 20505045 ER PT J AU Chun, YHP Yamakoshi, Y Yamakoshi, F Fukae, M Hu, JCC Bartlett, JD Simmer, JP AF Chun, Y. -H. P. Yamakoshi, Y. Yamakoshi, F. Fukae, M. Hu, J. C. -C. Bartlett, J. D. Simmer, J. P. TI Cleavage Site Specificity of MMP-20 for Secretory-stage Ameloblastin SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE proteases; enamel; tooth; fluorescent peptides ID AMELOGENESIS IMPERFECTA PHENOTYPE; SHEATH PROTEINS; CALCIUM-BINDING; ENAMEL PROTEINS; IMMATURE ENAMEL; MICE DISPLAY; RAT INCISOR; PORCINE; EXPRESSION; CLONING AB Ameloblastin is processed by protease(s) during enamel formation. We tested the hypothesis that MMP-20 (enamelysin) catalyzes the cleavages that generate secretory-stage ameloblastin cleavage products. We isolated a 23-kDa ameloblastin cleavage product from developing enamel and determined its N-terminus sequence. Ameloblastin was stably expressed and secreted from HEK293-H cells, purified, and digested with MMP-20 or Klk4 (kallikrein 4). The digests were analyzed by SDS-PAGE and Western blotting, and cleavage products were characterized by N-terminal sequencing. Six fluorescent peptides were digested with MMP-20 and Klk4 and analyzed by RP-HPLC and by mass spectrometry. MMP-20 cleaved each peptide exactly at the sites corresponding to ameloblastin cleavages catalyzed in vivo. Klk4 cleaved ameloblastin and the fluorescent peptides at sites not observed in vivo, and cleaved at only a single correct site: before Leu(171). We conclude that MMP-20 is the enzyme that processes ameloblastin during the secretory stage of amelogenesis, and we present a hypothesis about the sequence of ameloblastin cleavages. C1 [Chun, Y. -H. P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA. [Fukae, M.] Tsurumi Univ, Sch Dent Med, Dept Biochem, Tsurumi Ku, Yokohama, Kanagawa 230, Japan. [Bartlett, J. D.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. [Chun, Y. -H. P.; Yamakoshi, Y.; Yamakoshi, F.; Hu, J. C. -C.; Simmer, J. P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. RP Simmer, JP (reprint author), Univ Michigan, Dent Res Lab, 1210 Eisenhower Pl, Ann Arbor, MI 48108 USA. EM jsimmer@umich.edu FU NIDCR/NIH [DE015846, DE0 16276] FX We thank Mr. Tom Forton, Manager of the Michigan State University Meat Laboratory, for assistance in obtaining fresh developing molars from pigs slaughtered at that facility; Dr. Myron Crawford, Director of the W. M. Keck Foundation Bio technology Resource Laboratory at Yale University, and Nancy Williams for protein sequencing; and David Allen of NextGen Sciences, Inc., for mass spectrometry. This research was supported by USPHS Research Grants DE015846 and DE0 16276 (NIDCR/NIH). All authors declare that there are no conflicting interests. NR 35 TC 31 Z9 31 U1 0 U2 5 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 AUG PY 2010 VL 89 IS 8 BP 785 EP 790 DI 10.1177/0022034510366903 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 629JY UT WOS:000280194800005 PM 20400724 ER PT J AU Hoy, WE Ingelfinger, JR Hallan, S Hughson, MD Mott, SA Bertram, JF AF Hoy, W. E. Ingelfinger, J. R. Hallan, S. Hughson, M. D. Mott, S. A. Bertram, J. F. TI The early development of the kidney and implications for future health SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Review DE kidney development ID LOW-BIRTH-WEIGHT; MATERNAL PROTEIN RESTRICTION; AUSTRALIAN ABORIGINAL COMMUNITY; INTRAUTERINE GROWTH-RETARDATION; INDIVIDUAL GLOMERULAR VOLUMES; SHORT PRENATAL EXPOSURE; ISCHEMIC-HEART-DISEASE; CHRONIC-RENAL-FAILURE; MICE LACKING GDNF; BLOOD-PRESSURE C1 [Hoy, W. E.; Mott, S. A.] Univ Queensland, Ctr Chron Dis, Herston, Qld 4029, Australia. [Ingelfinger, J. R.] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Ingelfinger, J. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hallan, S.] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Trondheim, Norway. [Hughson, M. D.] Univ Mississippi, Med Ctr, Dept Pathol, Jackson, MS 39216 USA. [Bertram, J. F.] Monash Univ, Dept Anat & Dev Biol, Melbourne, Vic 3004, Australia. RP Hoy, WE (reprint author), Univ Queensland, Ctr Chron Dis, Royal Brisbane& Womens Hosp, Hlth Sci Bldg Level 8, Herston, Qld 4029, Australia. EM w.hoy@uq.edu.au RI Hoy, Wendy/A-7325-2010; mott, susan/F-6262-2010; Bertram, John/I-2588-2014 OI Hoy, Wendy/0000-0002-8405-1539; mott, susan/0000-0003-0117-4718; Bertram, John/0000-0001-5863-6464 NR 177 TC 42 Z9 53 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD AUG PY 2010 VL 1 IS 4 BP 216 EP 233 DI 10.1017/S204017441000022X PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 755DO UT WOS:000289907100002 PM 25141870 ER PT J AU Manini, AF McAfee, AT Noble, VE Bohan, JS AF Manini, Alex F. McAfee, Andrew T. Noble, Vicki E. Bohan, J. Stephen TI PROGNOSTIC VALUE OF THE DUKE TREADMILL SCORE FOR EMERGENCY DEPARTMENT PATIENTS WITH CHEST PAIN SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE treadmill test; myocardial infarction; chest pain ID CORONARY-ARTERY DISEASE; ASSOCIATION TASK-FORCE; PRACTICE GUIDELINES COMMITTEE; AMERICAN-HEART-ASSOCIATION; ACUTE CARDIAC ISCHEMIA; CHRONIC STABLE ANGINA; LOW-RISK PATIENTS; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; EXERCISE SCORE AB Background: The potential clinical utility of the Duke Treadmill Score (DTS) in the Emergency Department (ED) to risk-stratify patients with chest pain but negative cardiac biomarkers and non-diagnostic electrocardiograms is unclear. Objective: We evaluated whether DTS was associated with 30-day adverse cardiac outcomes for low-risk ED patients with chest pain. Methods: For this prospective, observational cohort study, the primary outcome was any of the following at 30 days: cardiac death, myocardial infarction, or coronary revascularization. DTS risk categories (low, intermediate, high) were compared with 30-day cardiac outcomes. Results: We enrolled 191 patients, of whom 20 (10%) were lost to follow-up, leaving 171 patients (mean age 53.3 +/- 12.4 years, 54% female, 3.5% adverse event rate) for evaluation. Sensitivity and specificity of DTS for 30-day events were 83.3% and 71.5%, respectively, with a 99.2% negative predictive value (confidence interval 95.4-99.9) for 30-day event-free survival. Conclusions: In this cohort of low-risk ED patients with chest pain, DTS demonstrated excellent negative predictive value for 30-day event-free survival and facilitated safe disposition of a large subset of patients. (C) 2010 Elsevier Inc. C1 [Manini, Alex F.] Harvard Affiliated Emergency Med Residency, Boston, MA USA. [McAfee, Andrew T.; Bohan, J. Stephen] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Emergency Med, Boston, MA USA. [McAfee, Andrew T.] i3 Drug Safety, Auburndale, MA USA. [Noble, Vicki E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Manini, AF (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1620, New York, NY 10029 USA. FU Harvard Affiliated Emergency Medicine Residency; Dade Behring Corporation FX The study was supported by the Richard C. Wuerz Scholarship for emergency medicine research from the Harvard Affiliated Emergency Medicine Residency, and an unrestricted grant provided by the Dade Behring Corporation. NR 35 TC 9 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2010 VL 39 IS 2 BP 135 EP 142 DI 10.1016/j.jemermed.2007.12.034 PG 8 WC Emergency Medicine SC Emergency Medicine GA 643IY UT WOS:000281290000001 PM 19062225 ER PT J AU Yiadom, MYAB AF Yiadom, Maame Yaa Maya A. B. TI CLOPIDOGREL USE IN ST-ELEVATION MYOCARDIAL INFARCTION (STEMI) SO JOURNAL OF EMERGENCY MEDICINE LA English DT Letter ID ANTIPLATELET THERAPY C1 [Yiadom, Maame Yaa Maya A. B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yiadom, Maame Yaa Maya A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 5 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2010 VL 39 IS 2 BP 217 EP 218 DI 10.1016/j.jemermed.2008.08.025 PG 2 WC Emergency Medicine SC Emergency Medicine GA 643IY UT WOS:000281290000017 PM 19168312 ER PT J AU Pallin, DJ Sullivan, AF Auerbach, BS Camargo, CA AF Pallin, Daniel J. Sullivan, Ashley F. Auerbach, Bruce S. Camargo, Carlos A., Jr. TI ADOPTION OF INFORMATION TECHNOLOGY IN MASSACHUSETTS EMERGENCY DEPARTMENTS SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE information technology; patient safety; medical error; medical informatics; computerized patient order entry; decision support AB Background: Information technology improves outcomes (e.g., by reducing error), and universal implementation of electronic medical records throughout the United States is a national goal. Prior studies have shown low rates of implementation. Objectives: To assess the current state of acquisition and implementation of information technology tools in Massachusetts emergency departments (EDs). Methods: This was part of a larger survey that sought to describe various attributes of all non-federal Massachusetts EDs. We asked about implementation of technologies listed below, and report proportions (95% confidence intervals) and medians (interquartile ranges). We compare responding to non-responding EDs to guard against response bias. Results: We identified and surveyed 74 non-federal EDs; 61 (82%) responded. Of these, the following number (%) reported full implementation of the following technologies: medication ordering, 9 (15%); medication error checking, 7 (11%); current visit information (e.g., chief complaint), 25 (41 %); computerized management recommendations based on clinical decision rules, 6 (10%); electronic laboratory results, 55 (90%); computerized clinical reminders, 10 (17%); tracking information, 31 (51%); hospital discharge summaries, 50 (82%); current outpatient medications, 15 (25%); ED visit notes, 30 (49%); radiographic images from a prior visit, 39 (64%); old electrocardiograms, 33 (54%); and computer system to collect real-time clinical data, 23 (38%). Conclusion: Massachusetts EDs have been slow to adopt evidence-based information technologies. A collaborative approach to determining the best available technologies and their implementation would decrease duplication of effort, frustration, and financial waste (due to non-implementation of acquired systems), and would facilitate inter-operability of ED computer systems. (C) 2010 Elsevier Inc. C1 [Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Pallin, Daniel J.] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Auerbach, Bruce S.] Sturdy Mem Hosp, Dept Emergency Med, Attleboro, MA USA. RP Pallin, DJ (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 9 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2010 VL 39 IS 2 BP 240 EP 243 DI 10.1016/j.jemermed.2008.09.030 PG 4 WC Emergency Medicine SC Emergency Medicine GA 643IY UT WOS:000281290000022 PM 19232877 ER PT J AU El Muayed, M Billings, LK Raja, MR Zhang, XM Park, PJ Newman, MV Kaufman, DB O'Halloran, TV Lowe, WL AF El Muayed, Malek Billings, Liana K. Raja, Meera R. Zhang, Xiaomin Park, Paul J. Newman, Marsha V. Kaufman, Dixon B. O'Halloran, Thomas V. Lowe, William L., Jr. TI Acute cytokine-mediated downregulation of the zinc transporter ZnT8 alters pancreatic beta-cell function SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; ACRODERMATITIS-ENTEROPATHICA GENE; INDUCIBLE INSULIN-SECRETION; ACTIVATED PROTEIN-KINASES; NITRIC-OXIDE; GLUCOSE-HOMEOSTASIS; NEURONAL DEATH; FASTING GLUCOSE; RAT THYMOCYTES; RISK LOCI AB Genetic studies suggest that Zn transporters such as ZnT8 play a role in insulin secretion by pancreatic beta-cells; however, little is known about the dynamic roles of Zn trafficking pathways on beta-cell physiology. To test the acute effects of the inflammatory cytokines interleukin 1 beta (IL1 beta) and tumor necrosis factor alpha (TNF alpha) on Zn homeostasis, the mRNA expression profile of Zn transporters of the ZnT and ZIP families was examined. Exposure of MIN6 cells or primary murine islets to IL1 beta or TNF alpha altered the mRNA expression profile of Zn transporters; most notable was decreased ZnT8 mRNA levels. siRNA-mediated gene knockdown was used to examine the effects of decreased ZnT8 expression in primary dispersed murine islet cells from C57/BL6 mice and MIN6 cells. ZnT8 knockdown in these murine islets led to reduced glucose stimulated insulin secretion without altering the total cellular insulin content or cell viability at normal or supraphysiological Zn concentrations. The labile Zn content determined by flow cytometry after loading with the Zn-specific sensor FluoZin-3 AM was decreased in MIN6 cells following ZnT8 knockdown or IL1 beta treatment. These results suggest that an acute decrease in ZnT8 levels impairs beta-cell function and Zn homeostasis, and may contribute to inflammatory cytokine-induced alterations in beta-cell function. Journal of Endocrinology (2010) 206, 159-169 C1 [El Muayed, Malek; Newman, Marsha V.; Lowe, William L., Jr.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. [Billings, Liana K.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raja, Meera R.; O'Halloran, Thomas V.] Northwestern Univ, Chem Life Proc Inst, Evanston, IL 60208 USA. [Raja, Meera R.; O'Halloran, Thomas V.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA. [Zhang, Xiaomin; Kaufman, Dixon B.] Northwestern Univ, Feinberg Sch Med, Div Transplant Surg, Chicago, IL 60611 USA. RP El Muayed, M (reprint author), Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, 303 E Chicago Ave,Tarry 15-755, Chicago, IL 60611 USA. EM m-muayed@northwestern.edu FU Northwestern Memorial Foundation; NIH [R37GM038784, U42RR023245, T32 DK007169-27]; CCSG [P30 CA060553]; NASA Ames Research Center [NNA04CC36G] FX This study was funded by a Northwestern Memorial Foundation MD-Scientist Fellowship in Genetic Medicine award for ME. The study was also funded by two NIH grants: R37GM038784 (TVO) and U42RR023245 (TVO) and T32 DK007169-27 NRSA Institutional Training Grant (LKB). Imaging was performed at the Northwestern University Cell Imaging Facility generously supported by CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. ICP-MS Metal analysis was performed at the Northwestern University Quantitative Bioelemental Imaging Center generously supported by NASA Ames Research Center NNA04CC36G. NR 75 TC 31 Z9 31 U1 0 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD AUG PY 2010 VL 206 IS 2 BP 159 EP 169 DI 10.1677/JOE-09-0420 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 626BM UT WOS:000279940900002 PM 20508080 ER PT J AU Ayotte, BJ Kressin, NR AF Ayotte, Brian J. Kressin, Nancy R. TI Race Differences in Cardiac Catheterization: The Role of Social Contextual Variables SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE race; differences; cardiac; catheterization ID RACIAL-DIFFERENCES; DECISION-MAKING; PREFERENCES; DISPARITIES; HEALTH; CARE; EXPERIENCES; BELIEFS; DISEASE; SURGERY AB Race differences in the receipt of invasive cardiac procedures are well-documented but the etiology remains poorly understood. We examined how social contextual variables were related to race differences in the likelihood of receiving cardiac catheterization in a sample of veterans who were recommended to undergo the procedure by a physician. Prospective observational cohort study. A subsample from a study examining race disparities in cardiac catheterization of 48 Black/African American and 189 White veterans who were recommended by a physician to undergo cardiac catheterization. We assessed social contextual variables (e.g., knowing somebody who had the procedure, being encouraged by family or friends), clinical variables (e.g., hypertension, maximal medical therapy), and if participants received cardiac catheterization at any point during the study. Blacks/African Americans were less likely to undergo cardiac catheterization compared to Whites even after controlling for age, education, and clinical variables (OR = 0.31; 95% CI, 0.13, 0.75). After controlling for demographic and clinical variables, three social contextual variables were significantly related to increased likelihood of receiving catheterization: knowing someone who had undergone the procedure (OR = 3.14; 95% CI, 1.70, 8.74), social support (OR = 2.05; 95% CI, 1.17, 2.78), and being encouraged by family to have procedure (OR = 1.45; 95% CI, 1.08, 1.90). After adding the social contextual variables, race was no longer significantly related to the likelihood of receiving catheterization, thus suggesting that social context plays an important role in the relationship between race and cardiac catheterization. Our results suggest that social contextual factors are related to the likelihood of receiving recommended care. In addition, accounting for these relationships attenuated the observed race disparities between Whites and Blacks/African Americans who were recommended to undergo cardiac catheterization by their physicians. C1 [Ayotte, Brian J.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA 02130 USA. [Kressin, Nancy R.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Boston, MA USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Hlth Care Dispar Res Program, Boston, MA 02118 USA. RP Ayotte, BJ (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, 150 S Huntington Ave 152M, Boston, MA 02130 USA. EM brian.ayotte@va.gov OI Kressin, Nancy/0000-0003-2767-4286 FU VA Health Services Research and Development Service (HSRD) [ECV97-022] FX This research was supported by funding from the VA Health Services Research and Development Service (HSR & D; ECV97-022, N. Kressin, P. I.). Dr. Kressin is a Research Career Scientist, VA HSR&D (RCS 02-066-1); Dr. Ayotte is a VA HSR&D Post-doctoral fellow. 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 22 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2010 VL 25 IS 8 BP 814 EP 818 DI 10.1007/s11606-010-1324-y PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 620MZ UT WOS:000279505300017 PM 20383600 ER PT J AU Manze, M Rose, AJ Orner, MB Berlowitz, DR Kressin, NR AF Manze, Meredith Rose, Adam J. Orner, Michelle B. Berlowitz, Dan R. Kressin, Nancy R. TI Understanding Racial Disparities in Treatment Intensification for Hypertension Management SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE disparities; treatment intensification; hypertension ID BLOOD-PRESSURE CONTROL; UNITED-STATES; COGNITIVE REPRESENTATION; MEDICATION ADHERENCE; THERAPEUTIC INERTIA; PREVALENCE; AWARENESS; BELIEFS; CARE; QUESTIONNAIRE AB Disparities in blood pressure (BP) control may be a function of disparities in treatment intensification (TI). To examine racial differences in TI, understand modifiable factors that may mediate this relationship, and explore the relative effects of TI and race on blood pressure. Prospective cohort study. Participants were 819 black and white patients with hypertension from an urban, safety-net hospital We sequentially explored the effects of patient race, sociodemographic and clinical characteristics, beliefs about BP/medications, perceptions of provider/discrimination, sodium intake, medication adherence, and provider counseling on TI, performing a series of random effects analyses. To assess the effects of race and TI on BP, we performed linear regressions, using systolic BP (SBP) as the outcome. Unadjusted analyses and those including sociodemographic and clinical characteristics revealed that black patients had less TI than whites (-0.31 vs.-0.24, p < 0.001), but adjustment for patient beliefs and experiences eliminated the effects of race (beta =-0.02, p = 0.5). Increased patient concerns about BP medications were related to lower TI, as was more provider counseling (beta =-0.06, p = 0.02 and beta = -0.01, p = 0.001, respectively). In the unadjusted analysis, black race was a significant predictor of SBP (134 mm/Hg for blacks vs. 131 mm/Hg for whites, p = 0.009), but when both race and TI were included in the model, TI was a significant predictor of SBP (final SBP 2.0 mm/Hg lower for each additional therapy increase per 10 visits, p < 0.001), while race was not (Blacks 1.6 mm/Hg higher than whites, p = 0.17). Improved patient-provider communication targeted towards addressing patient concerns about medications may have the potential to reduce racial disparities in TI and ultimately, BP control. C1 [Manze, Meredith; Rose, Adam J.; Kressin, Nancy R.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Manze, Meredith; Berlowitz, Dan R.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02118 USA. [Rose, Adam J.; Orner, Michelle B.; Berlowitz, Dan R.; Kressin, Nancy R.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Manze, Meredith; Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. RP Manze, M (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM meredith.manze@bmc.org OI Kressin, Nancy/0000-0003-2767-4286 FU NIH/National Heart, Lung and Blood Institute [R01 HL072814]; Department of Veterans Affairs Health Services Research and Development Service FX This work was supported by the NIH/National Heart, Lung and Blood Institute grant R01 HL072814 (N. Kressin, PI). Dr. Kressin is supported in part by a Research Career Scientist Award from the Department of Veterans Affairs Health Services Research and Development Service. Dr. Rose is funded by a career development award from the Department of Veterans Affairs Health Services Research and Development Service. NR 28 TC 12 Z9 12 U1 0 U2 13 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 AUG PY 2010 VL 25 IS 8 BP 819 EP 825 DI 10.1007/s11606-010-1342-9 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 620MZ UT WOS:000279505300018 PM 20386998 ER PT J AU Pabon-Nau, LP Cohen, A Meigs, JB Grant, RW AF Pabon-Nau, Lina P. Cohen, Amy Meigs, James B. Grant, Richard W. TI Hypertension and Diabetes Prevalence Among US Hispanics by Country of Origin: The National Health Interview Survey 2000-2005 SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 09-12, 2008 CL Pittsburgh, PA SP Soc Gen Internal Med DE diabetes; health status; hypertension; immigrant health; vulnerable populations ID NUTRITION-EXAMINATION-SURVEY; SELF-REPORTED HYPERTENSION; SAN-ANTONIO HEART; CARDIOVASCULAR-DISEASE; MEXICAN-AMERICANS; UNITED-STATES; PUERTO-RICANS; METABOLIC SYNDROME; CUBAN AMERICANS; RISK-FACTORS AB Despite their diverse cultural origins, Hispanics in the US are generally studied as a single ethnic group. 1) Assess demographic and disease-related differences among U.S. Hispanics by country of origin, and 2) Examine the mediating roles of socioeconomic status and acculturation on disease prevalence in these subgroups. Using data from the 2000-2005 National Health Interview Survey (NHIS), we compared characteristics of Mexican-Americans with Hispanics originally from: Mexico, Puerto Rico, Central/South America, Cuba, and Dominican Republic (n = 31,240). We stratified the analysis by foreign versus US-born Hispanic subgroups and modeled hypertension and diabetes prevalence, adjusting for demographic and acculturation differences. The six Hispanic subgroups were significantly diverse in all measured variables. Prevalence of hypertension (32%) and diabetes (15%) was highest in foreign-born Puerto Ricans. After adjusting for age, BMI, smoking, socioeconomic status and acculturation in foreign-born Hispanics, Puerto Ricans (OR = 1.76 [95% CI: 1.23, 2.50], p = 0.002) and Dominicans (OR = 1.93 [1.24, 3.00], p = 0.004), had higher prevalence of hypertension relative to Mexican-Americans. Adjusted diabetes prevalence among foreign-born Hispanics was half or less in Cubans (OR = 0.42 [0.25, 0.68] p < 0.001), Dominicans (OR = 0.48 [0.26, 0.91], p = 0.02) and Central/South Americans (OR = 0.51 [0.33, 0.78], p = 0.002) relative to Mexican-Americans. Among US-born Hispanic subgroups, Cubans had lower hypertension (OR = 0.53, [0.33, 0.83], p = 0.006) and Mexicans (OR = 0.76 [0.60, 0.98], p = 0.03) had lower diabetes prevalence compared to Mexican-Americans in adjusted models. The prevalence of hypertension and diabetes varies significantly among Hispanics by country of origin. Health disparities research should include representation from all Hispanic subgroups. C1 [Pabon-Nau, Lina P.; Meigs, James B.; Grant, Richard W.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Cohen, Amy] Harvard Univ, Sch Publ Hlth, Dept Informat Technol, Boston, MA 02115 USA. [Pabon-Nau, Lina P.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. RP Pabon-Nau, LP (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM lpabon1@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK067452, K24 DK080140]; PHS HHS [NIDDK K24 DK080140, T32HP11001] NR 43 TC 42 Z9 42 U1 3 U2 8 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 AUG PY 2010 VL 25 IS 8 BP 847 EP 852 DI 10.1007/s11606-010-1335-8 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 620MZ UT WOS:000279505300022 PM 20490949 ER PT J AU Dublin, S Glazer, NL Smith, NL Psaty, BM Lumley, T Wiggins, KL Page, RL Heckbert, SR AF Dublin, Sascha Glazer, Nicole L. Smith, Nicholas L. Psaty, Bruce M. Lumley, Thomas Wiggins, Kerri L. Page, Richard L. Heckbert, Susan R. TI Diabetes Mellitus, Glycemic Control, and Risk of Atrial Fibrillation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE arrhythmia; atrial fibrillation; diabetes mellitus; glycemic control; diabetes complications ID C-REACTIVE PROTEIN; OBSTRUCTIVE SLEEP-APNEA; INSULIN SENSITIVITY; GLUCOSE-METABOLISM; INDEPENDENT RISK; PREVALENCE; POPULATION; OBESITY; HEART; OLDER AB Diabetes may be an independent risk factor for atrial fibrillation. However, results from prior studies are in conflict, and no study has examined diabetes duration or glycemic control. To examine the association of diabetes with risk of atrial fibrillation and to describe risk according to diabetes duration and glycemic control. A population-based case-control study. Within a large, integrated healthcare delivery system, we identified 1,410 people with newly-recognized atrial fibrillation from ICD-9 codes and validated cases by review of medical records. 2,203 controls without atrial fibrillation were selected from enrollment lists, stratified on age, sex, hypertension, and calendar year. Information on atrial fibrillation, diabetes and other characteristics came from medical records. Diabetes was defined based on physician diagnoses recorded in the medical record, and pharmacologically treated diabetes was defined as receiving antihyperglycemic medications. Information about hemoglobin A1c levels came from computerized laboratory data. Among people with atrial fibrillation, 252/1410 (17.9%) had pharmacologically treated diabetes compared to 311/2203 (14.1%) of controls. The adjusted OR for atrial fibrillation was 1.40 (95% CI 1.15-1.71) for people with treated diabetes compared to those without diabetes. Among those with treated diabetes, the risk of developing atrial fibrillation was 3% higher for each additional year of diabetes duration (95% CI 1-6%). Compared to people without diabetes, the adjusted OR for people with treated diabetes with average hemoglobin A1c a parts per thousand currency sign7 was 1.06 (95% CI 0.74-1.51); for A1c > 7 but a parts per thousand currency sign8, 1.48 (1.09-2.01); for A1c > 8 but a parts per thousand currency sign9, 1.46 (1.02-2.08); and for A1c > 9, 1.96 (1.22-3.14). Diabetes was associated with higher risk of developing atrial fibrillation, and risk was higher with longer duration of treated diabetes and worse glycemic control. Future research should identify and test approaches to reduce the risk of atrial fibrillation in people with diabetes. C1 [Dublin, Sascha; Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Dublin, Sascha; Smith, Nicholas L.; Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Glazer, Nicole L.; Psaty, Bruce M.; Wiggins, Kerri L.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Page, Richard L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI USA. [Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Dublin, S (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM dublin.s@ghc.org FU National Heart, Lung and Blood Institute [HL 68986, HL 43201, HL 73410, HL 68639]; Veterans' Affairs Health Services Research Development; National Institute on Aging [K23AG028954]; Group Health Research Institute; American Federation for Aging Research; Hartford Foundation; Atlantic Philanthropies; Starr Foundation FX This research was funded by grants HL 68986, HL 43201, HL 73410, and HL 68639 from the National Heart, Lung and Blood Institute. Dr. Dublin was funded through a Veterans' Affairs Health Services Research & Development fellowship, a Paul Beeson Career Development Award from the National Institute on Aging (K23AG028954), and Group Health Research Institute internal funds. The Beeson Award is also supported in part by the American Federation for Aging Research, the Hartford Foundation, the Atlantic Philanthropies and the Starr Foundation. NR 40 TC 67 Z9 70 U1 1 U2 5 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 AUG PY 2010 VL 25 IS 8 BP 853 EP 858 DI 10.1007/s11606-010-1340-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 620MZ UT WOS:000279505300023 PM 20405332 ER PT J AU Keenan, CR Dhaliwal, G Henderson, MC Bowen, JL AF Keenan, Craig R. Dhaliwal, Gurpreet Henderson, Mark C. Bowen, Judith L. TI A 43-Year-Old Woman with Abdominal Pain and Fever SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE pattern recognition; analytic reasoning; problem representation; clinical diagnostic reasoning C1 [Keenan, Craig R.; Henderson, Mark C.] UC Davis Med Ctr, Dept Internal Med, Sacramento, CA 95817 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. [Bowen, Judith L.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. RP Keenan, CR (reprint author), UC Davis Med Ctr, Dept Internal Med, 4150 V St,Suite 2400, Sacramento, CA 95817 USA. EM craig.keenan@ucdmc.ucdavis.edu NR 7 TC 5 Z9 5 U1 0 U2 1 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 AUG PY 2010 VL 25 IS 8 BP 874 EP 877 DI 10.1007/s11606-010-1372-3 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 620MZ UT WOS:000279505300027 PM 20440575 ER PT J AU Bray-Hall, S Schmidt, K Aagaard, E AF Bray-Hall, Susan Schmidt, Katrina Aagaard, Eva TI Toward Safe Hospital Discharge: A Transitions in Care Curriculum for Medical Students SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE care transitions; curriculum development/evaluation; home visit; undergraduate medical education; hospital discharge ID RANDOMIZED CONTROLLED-TRIAL; FOLLOW-UP; INTERVENTION; QUALITY; EVENTS; NEEDS AB Medical errors often occur when patients move between care settings. Physicians generally receive little formal education on improving patient care transitions. To develop a sustainable and effective Transition in Care Curriculum (TICC). Specific goals were to increase student confidence in and knowledge of skills necessary during care transitions at the time of hospital discharge, and to quantify the frequency of student-identified medication discrepancies during a post-discharge home visit. TICC was delivered to 136 3rd-year medical students during their required inpatient medicine clerkship at six urban Denver hospitals. TICC consists of small and large group interactive sessions and self-directed learning exercises to provide foundational knowledge of care transitions. Experiential learning occurs through direct patient care at the time of discharge and during a follow-up home, hospice, or skilled nursing visit. Students completed a pre-post confidence measure, short answer and multiple choice questions, a post-clerkship satisfaction survey, and a standardized medication discrepancy tool. Overall combined confidence in transitional care skills improved following the TICC from an average score of 2.7 (SD 0.9) to 4.0 (SD 0.8) (p < 0.01) on a 5-point confidence scale. They scored an average of 77% on the written discharge plan portion of the final exam. Students rated the usefulness of TICC at a mean of 3.1 (SD 0.7), above the combined mean of 2.7 for project work in all required clerkships. Students identified medication discrepancies during 43% of post-discharge visits (58 of 136). The most common reasons for discrepancies were patient lack of understanding of instructions and intentional non-adherence to medication plan. TICC represents a feasible and effective program to teach evidence-based transitional care. C1 [Bray-Hall, Susan] Denver VA Med Ctr, Denver, CO 80220 USA. [Bray-Hall, Susan] Univ Colorado, Dept Med, Div Geriatr, Aurora, CO USA. [Schmidt, Katrina] St Joseph Hosp, Dept Surg, Denver, CO USA. RP Bray-Hall, S (reprint author), Denver VA Med Ctr, 1055 Clermont St 111-D, Denver, CO 80220 USA. EM Susan.Bray-Hall@va.gov FU John A. Hartford Foundation, Center of Excellence, Division of Geriatrics, University of Colorado; John A. Hartford Center of Excellence, University of Colorado Denver FX Dr. Bray-Hall has received funding from the John A. Hartford Foundation, Center of Excellence, Division of Geriatrics, University of Colorado.; No sponsors or funders were involved in curricula design, data collection, management, analysis and interpretation, or the preparation, review and approval of the manuscript. This protocol was approved by the Colorado and VA IRB as exempt.; This study was supported by a grant from the John A. Hartford Center of Excellence, University of Colorado Denver. The authors wish to thank Dr. Adam Abraham who helped secure the grant and Drs. Daniel Matlock, Ethan Cumbler, and Jeannette Guerrasio for facilitating the small group sessions. NR 21 TC 20 Z9 20 U1 2 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 AUG PY 2010 VL 25 IS 8 BP 878 EP 881 DI 10.1007/s11606-010-1364-3 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 620MZ UT WOS:000279505300028 PM 20443072 ER PT J AU Boulton, CL Salzler, M Mudgal, CS AF Boulton, Christina L. Salzler, Matthew Mudgal, Chaitanya S. TI Intramedullary Cannulated Headless Screw Fixation of a Comminuted Subcapital Metacarpal Fracture: Case Report SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Fixation; fracture; intramedullary; metacarpal; subcapital ID PHALANGEAL FRACTURES; PLATE FIXATION; DISTAL RADIUS; HAND AB This case report describes an alternative technique for the fixation of displaced comminuted subcapital fractures of the metacarpal with limited distal bone stock. Using a cannulated headless screw as an intramedullary device placed through the articular surface, we were able to secure proximal and distal bone purchase without excessive soft tissue stripping or disruption of the fracture hematoma. This technique allows early rehabilitation, and our patient went on to uneventful healing with excellent functional results. (J Hand Surg 2010; 35A:1260-1263. (C) 2010 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Mudgal, Chaitanya S.] Harvard Univ, Orthopaed Hand Serv, Massachusetts Gen Hosp,Yawkey Ctr,Med Sch, Harvard Combined Orthopaed Residency Program, Boston, MA 02114 USA. Harvard Univ, Orthopaed Hand Serv, Massachusetts Gen Hosp,Med Sch, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Harvard Univ, Orthopaed Hand Serv, Massachusetts Gen Hosp,Yawkey Ctr,Med Sch, Harvard Combined Orthopaed Residency Program, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org NR 13 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD AUG PY 2010 VL 35A IS 8 BP 1260 EP 1263 DI 10.1016/j.jhsa.2010.04.032 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 637MS UT WOS:000280822800005 PM 20619555 ER PT J AU Ring, D Barth, R Barsky, A AF Ring, David Barth, Robert Barsky, Arthur TI Evidence-Based Medicine: Disproportionate Pain and Disability SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Editorial Material C1 [Ring, David] Harvard Univ, Dept Orthopaed Surg, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Med Sch, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Parkridge Hosp, Chattanooga, TN USA. RP Ring, D (reprint author), Harvard Univ, Dept Orthopaed Surg, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Med Sch, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 15 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD AUG PY 2010 VL 35A IS 8 BP 1345 EP 1347 DI 10.1016/j.jhsa.2010.06.007 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 637MS UT WOS:000280822800021 PM 20684932 ER PT J AU Delahanty, LM AF Delahanty, L. M. TI An expanded role for dietitians in maximising retention in nutrition and lifestyle intervention trials: implications for clinical practice SO JOURNAL OF HUMAN NUTRITION AND DIETETICS LA English DT Review DE diabetes; lifestyle intervention; obesity; retention ID DIABETES PREVENTION PROGRAM; CARDIOVASCULAR-DISEASE; COMPLICATIONS TRIAL; REDUCTION; WEIGHT; DESIGN AB The demand for clinical trials targeting lifestyle intervention has increased as a result of the escalation in obesity, diabetes mellitus and cardiovascular disease. Little is published about the strategies that dietitians have used to successfully screen potential study volunteers, implement interventions and maximise adherence and retention in large multicentre National Institutes of Health funded nutrition and lifestyle intervention clinical trials. This paper discusses an expanded role for the contributions of dietitians as members of an interdisciplinary team based on research experiences in the Diabetes Control and Complications Trial, Diabetes Prevention Program and Look AHEAD (Action for Health in Diabetes). Many of the strategies and insights discussed are also relevant to effective clinical practice. Dietitians need to broaden their scope of practice so that they are integrated proactively into the screening and intervention phases of large clinical trials to maximise retention and adherence to assigned nutrition, lifestyle and behavioural interventions. The skills of dietitians are a unique fit for this work and it is important that investigators and project managers consider including them in both the screening and intervention phases of such clinical trials to maximise retention results. C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Delahanty, LM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Suite 340,50 Staniford St, Boston, MA 02114 USA. EM ldelahanty@partners.org NR 23 TC 12 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3871 EI 1365-277X J9 J HUM NUTR DIET JI J. Hum. Nutr. Diet. PD AUG PY 2010 VL 23 IS 4 BP 336 EP 343 DI 10.1111/j.1365-277X.2009.01037.x PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 626AL UT WOS:000279937900002 PM 20163510 ER PT J AU Delahanty, LM AF Delahanty, L. M. TI Research charting a course for evidence-based clinical dietetic practice in diabetes SO JOURNAL OF HUMAN NUTRITION AND DIETETICS LA English DT Review DE diabetes; lifestyle intervention; obesity; retention ID LIFE-STYLE INTERVENTION; IMPAIRED GLUCOSE-TOLERANCE; PREVENTION-PROGRAM; COMPLICATIONS TRIAL; INTENSIVE THERAPY; CARDIOVASCULAR-DISEASE; WEIGHT-LOSS; MELLITUS; METFORMIN; DESIGN AB Nutrition and lifestyle interventions have been a critical component in three of the four largest clinical trials that focused on diabetes in the past two decades. Evidence of the effectiveness of nutrition and lifestyle interventions with resepect to achieving diabetes-related outcomes for diabetes prevention and a reduction in diabetes complications for people with diabetes is clearly mounting. The Diabetes Control and Complications Trial (1983-1993), the Diabetes Prevention Program (1996-2001) and the Look AHEAD (Action for Health in Diabetes) Trial (2001-2012) have been providing key evidence for the dietitian's role in delivering effective nutrition and lifestyle interventions for people with prediabetes, type 1 and type 2 diabetes. The dietitians in these multicentre efficacy trials contributed to this evidence base by expanding their roles beyond implementing the protocol defined goal-based nutrition and lifestyle interventions to conducting ancillary research and using problem-solving strategies that tailor counselling approaches toward participants' barriers to goal achievement. As lifestyle coaches and case managers, dietitians had the opportunity to work with the same group of study participants over extended periods of time and use their clinical and research expertise to uncover important insights and strategies that helped achieve clinical goals related to glycaemia control, weight loss and activity. The present review will 'chart the course' of how the evidence base for nutrition and lifestyle interventions emanated from these trials and discuss the implications for clinical dietetic practice. Dietitians can use insights gleaned from these experiences with the research process to expand their roles and guide cutting edge evidence-based clinical dietetic practice in diabetes. C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Delahanty, LM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St Suite 340, Boston, MA 02114 USA. EM ldelahanty@partners.org NR 41 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3871 EI 1365-277X J9 J HUM NUTR DIET JI J. Hum. Nutr. Diet. PD AUG PY 2010 VL 23 IS 4 BP 360 EP 370 DI 10.1111/j.1365-277X.2010.01065.x PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 626AL UT WOS:000279937900005 PM 20456590 ER PT J AU Breen, N Rao, SR Meissner, HI AF Breen, Nancy Rao, Sowmya R. Meissner, Helen I. TI Immigration, Health Care Access, and Recent Cancer Tests Among Mexican-Americans in California SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Mexican-American; Mammography; Pap; FOBT; Colorectal endoscopy; Access to care; Immigration; Language; Cancer testing; CHIS ID UNITED-STATES; SCREENING PRACTICES; HISPANIC WOMEN; INTERVIEW SURVEY; BEHAVIORAL-MODEL; ASIAN-AMERICAN; BREAST; ACCULTURATION; INSURANCE; LANGUAGE AB Immigrants' lower rates of cancer testing may be due to lack of fluency in English and other skills and knowledge about navigating US health care markets, lack of access to health services, or both. We analyzed 9,079 Mexican-American respondents to the 2001 California Health Interview Survey (CHIS) grouped as born in the US, living in the US 10 or more years, or living in the US less than 10 years. The CHIS provides the largest Mexican-American sample in a US survey. Access to care meant having health insurance coverage and a usual source of care. English proficiency meant the respondent took the interview in English. Multivariate logistic regression was used to predict outcomes. Respondents reporting more time in the US were more likely to report access to medical care and to report getting a cancer screening exam. Regardless of time in the US, respondents reporting access had similar test rates. Regression results indicate that time in the US and primary language were not significant relative to use of cancer screening tests, but access to care was. Cancer screening tests that are covered by Every Woman Counts, California's breast and cervical cancer early detection program, had smaller gaps among groups than colorectal cancer screening which is not covered by a program. California is the only state with a survey able to monitor changes in small population groups. Understanding barriers specific to subgroups is key to developing appropriate policy and interventions to increase use of cancer screening exams. C1 [Breen, Nancy] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD 20892 USA. [Rao, Sowmya R.] Massachusetts Gen Hosp, Inst Hlth Policy, Ctr Biostat, Boston, MA 02114 USA. [Meissner, Helen I.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Breen, N (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Rockville, MD 20892 USA. EM Breenn@mail.nih.gov NR 47 TC 14 Z9 14 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD AUG PY 2010 VL 12 IS 4 BP 433 EP 444 DI 10.1007/s10903-008-9198-3 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 645ZY UT WOS:000281505900002 PM 19052868 ER PT J AU Rabquer, BJ Amin, MA Teegala, N Shaheen, MK Tsou, PS Ruth, JH Lesch, CA Imhof, BA Koch, AE AF Rabquer, Bradley J. Amin, Mohammad A. Teegala, Nanditha Shaheen, Matthew K. Tsou, Pei-Suen Ruth, Jeffrey H. Lesch, Charles A. Imhof, Beat A. Koch, Alisa E. TI Junctional Adhesion Molecule-C Is a Soluble Mediator of Angiogenesis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; CELL-ADHESION; IMMUNOGLOBULIN SUPERFAMILY; ENDOTHELIAL-CELLS; E-SELECTIN; LEUKOCYTE ADHESION; GROWTH-FACTOR; IN-VIVO; JAM-C; PROTEIN AB Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed by endothelial cells (ECs) that plays a role in tight junction formation, leukocyte adhesion, and transendothelial migration. In the current study, we investigated whether JAM-C is found in soluble form and whether soluble JAM-C (sJAM-C) mediates angiogenesis. We found that JAM-C is present in soluble form in normal serum and elevated in rheumatoid arthritis (RA) serum. The concentration of sJAM-C is also elevated locally in RA synovial fluid compared with RA serum or osteoarthritis synovial fluid. sJAM-C was also present in the culture supernatant of human microvascular ECs (HMVECs) and immortalized human dermal microvascular ECs, and its concentration was increased following cytokine stimulation. In addition, sJAM-C cleavage from the cell surface was mediated in part by a disintegrin and metalloproteinases 10 and 17. In functional assays, sJAM-C was both chemotactic and chemokinetic for HMVECs and induced HMVEC tube formation on Matrigel in vitro. Neutralizing anti-JAM-C Abs inhibited RA synovial fluid-induced HMVEC chemotaxis and sJAM-C-induced HMVEC tube formation on Matrigel. sJAM-C also induced angiogenesis in vivo in the Matrigel plug and sponge granuloma models. Moreover, sJAM-C-mediated HMVEC chemotaxis was dependent on Src, p38, and PI3K. Our results show that JAM-C exists in soluble form and suggest that modulation of sJAM-C may provide a novel route for controlling pathological angiogenesis. The Journal of Immunology, 2010, 185: 1777-1785. C1 [Rabquer, Bradley J.] Univ Michigan, Sch Med, Div Rheumatol, Dept Med, Ann Arbor, MI 48109 USA. [Koch, Alisa E.] US Dept Vet Affairs, Vet Affairs Med Serv, Ann Arbor, MI 48109 USA. [Imhof, Beat A.] Univ Geneva, Dept Pathol, CH-1211 Geneva, Switzerland. RP Rabquer, BJ (reprint author), Univ Michigan, Sch Med, Div Rheumatol, Dept Med, 4388 BSRB,109 Zina Pitcher Dr, Ann Arbor, MI 48109 USA. EM brabquer@umich.edu RI Koch, Alisa/B-6894-2011 FU National Institutes of Health [HL094017, AR052482, AR48267]; Office of Research and Development, Medical Research Service, Department of Veterans Affairs; Frederick G.L. Huetwell and William D. Robinson FX This work was supported by National Institutes of Health Grants HL094017 (to B.J.R.), AR052482 (to M.A.A.), and AR48267 (to A.E.K.), the Office of Research and Development, Medical Research Service, Department of Veterans Affairs, and the Frederick G.L. Huetwell and William D. Robinson, M.D., Professorship in Rheumatology. NR 44 TC 27 Z9 31 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2010 VL 185 IS 3 BP 1777 EP 1785 DI 10.4049/jimmunol.1000556 PG 9 WC Immunology SC Immunology GA 629EI UT WOS:000280177400055 PM 20592283 ER PT J AU Carbo, C Duerschmied, D Goerge, T Hattori, H Sakai, J Cifuni, SM White, GC Chrzanowska-Wodnicka, M Luo, HR Wagner, DD AF Carbo, Carla Duerschmied, Daniel Goerge, Tobias Hattori, Hidenori Sakai, Jiro Cifuni, Stephen M. White, Gilbert C., II Chrzanowska-Wodnicka, Magdalena Luo, Hongbo R. Wagner, Denisa D. TI Integrin-independent role of CalDAG-GEFI in neutrophil chemotaxis SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Rap1; adhesion; F-actin; polarization ID BLOOD POLYMORPHONUCLEAR LEUKOCYTES; RANDOM LOCOMOTION; CLOSE QUARTERS; CELL-ADHESION; CAIDAG-GEFI; NULL MICE; ACTIVATION; RAP1B; INFLAMMATION; POLARIZATION AB Chemotaxis and integrin activation are essential processes for neutrophil transmigration in response to injury. CalDAG-GEFI plays a key role in the activation of beta 1, beta 2, and beta 3 integrins in platelets and neutrophils by exchanging a GDP for a GTP on Rap1. Here, we explored the role of CalDAG-GEFI and Rap1b in integrin-independent neutrophil chemotaxis. In a transwell assay, CalDAG-GEFI(-/-) neutrophils had a 46% reduction in transmigration compared with WT in response to a low concentration of LTB(4). Visualization of migrating neutrophils in the presence of 10 mM EDTA revealed that CalDAG-GEFI(-/-) neutrophils had abnormal chemotactic behavior compared with WT neutrophils, including reduced speed and directionality. Interestingly, Rap1b(-/-) neutrophils had a similar phenotype in this assay, suggesting that CalDAG-GEFI may be acting through Rap1b. We investigated whether the deficit in integrin-independent chemotaxis in CalDAG-GEFI(-/-) neutrophils could be explained by defective cytoskeleton rearrangement. Indeed, we found that CalDAG-GEFI(-/-) neutrophils had reduced formation of F-actin pseudopodia after LTB(4) stimulation, suggesting that they have a defect in polarization. Overall, our studies show that CalDAG-GEFI helps regulate neutrophil chemotaxis, independent of its established role in integrin activation, through a mechanism that involves actin cytoskeleton and cellular polarization. J. Leukoc. Biol. 88: 313-319; 2010. C1 [Carbo, Carla; Duerschmied, Daniel; Cifuni, Stephen M.; Wagner, Denisa D.] Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Carbo, Carla; Duerschmied, Daniel; Cifuni, Stephen M.; Wagner, Denisa D.] Harvard Univ, Sch Med, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Hattori, Hidenori; Sakai, Jiro; Luo, Hongbo R.] Harvard Univ, Sch Med, Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. [Carbo, Carla; Duerschmied, Daniel; Hattori, Hidenori; Sakai, Jiro; Luo, Hongbo R.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Goerge, Tobias] Univ Hosp Muenster, Dept Dermatol, Munster, Germany. [Hattori, Hidenori; Sakai, Jiro; Luo, Hongbo R.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [White, Gilbert C., II; Chrzanowska-Wodnicka, Magdalena] Blood Ctr Wisconsin, Blood Res Inst, Milwaukee, WI USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Immune Dis Inst, 3 Blackfan Circle, Boston, MA 02115 USA. EM wagner@idi.harvard.edu OI Sakai, Jiro/0000-0002-2526-2766; Chrzanowska-Wodnicka, Magdalena/0000-0003-4182-2126 FU National Heart, Lung and Blood Institute of the National Institutes of Health [P01 HL056949, P01 HL066105]; DFG [GO1360/4-1]; IMF Munster; NIH [HL085100, AI076471, HL092020, GM076084]; American Cancer Society FX This work was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health grants P01 HL056949 and P01 HL066105 (both to D. D. W.); grant DFG GO1360/4-1 and IMF Munster (T. G.); NIH grants HL085100, AI076471, HL092020, and GM076084; and a research scholar grant from the American Cancer Society (H. R. L.). We thank Kulandayan Subramanian and Ian del Conde for helpful discussions and Lesley Cowan for assistance in preparing the manuscript. We thank Ann Graybiel, David Housman, and Jill Crittenden for providing the CalDAG-GEFI-deficient mice. NR 35 TC 14 Z9 15 U1 0 U2 2 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 AUG PY 2010 VL 88 IS 2 BP 313 EP 319 DI 10.1189/jlb.0110049 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 692YQ UT WOS:000285192200011 PM 20413728 ER PT J AU Sun, PZ AF Sun, Phillip Zhe TI Simplified and scalable numerical solution for describing multi-pool chemical exchange saturation transfer (CEST) MRI contrast SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Amide proton transfer (APT); Chemical exchange saturation transfer (CEST); Numerical solution ID MAGNETIZATION-TRANSFER; PROTON-EXCHANGE; QUANTITATIVE DESCRIPTION; PARACEST AGENTS; CROSS-RELAXATION; WATER PROTONS; HUMAN BRAIN; IN-VIVO; RESONANCE; RATES AB Chemical exchange saturation transfer (CEST) imaging is sensitive to dilute labile proton and microenvironment properties such as pH and temperature, and provides vital information complementary to the conventional MRI methods. Whereas the Bloch equations coupled by exchange terms (i.e., Bloch-McConnell equations) have been utilized to quantify 2-pool CEST contrast, it is tedious to extend the Bloch-McConnell equations to describe CEST contrast beyond four saturation transfer sites. Hence, it is necessary to develop a scalable yet reasonably accurate numerical solution to describe the complex multi-pool CEST contrast. It is postulated here that the multi-pool CEST contrast can be quantified by modifying the classic 2-pool model. Although the direct exchange among labile proton groups is often negligible, labile protons may be coupled indirectly through their interaction with bulk water protons, which has to be quantified. The coupling term was solved empirically, and the proposed simplified solution was shown in good agreement with the conventional simulation. Moreover, the proposed solution is scalable, and can be easily extended to describe multi-pool CEST contrast. In sum, our study established a simplified and scalable, yet reasonably accurate numerical solution, suitable for quantitatively describing multi-pool CEST contrast. (C) 2010 Elsevier Inc. All rights reserved. C1 [Sun, Phillip Zhe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Sun, Phillip Zhe] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Sun, PZ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Ctr Biomed Imaging, Rm 2301,149 13th St, Charlestown, MA 02129 USA. EM pzhesun@nmr.mgh.harvard.edu FU AHA/SDG [0835384N]; NIH/NIBIB [1K01EB009771-01]; [NIH/R21NS061119-02] FX This study was supported in part by Grants from AHA/SDG 0835384N, NIH/NIBIB 1K01EB009771-01 and NIH/R21NS061119-02. NR 37 TC 29 Z9 29 U1 3 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD AUG PY 2010 VL 205 IS 2 BP 235 EP 241 DI 10.1016/j.jmr.2010.05.004 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 627SZ UT WOS:000280064500007 PM 20570196 ER PT J AU Emmer, BJ van Osch, MJ Wu, O Steup-Beekman, GM Steens, SC Huizinga, TW van Buchem, MA van der Grond, J AF Emmer, Bart J. van Osch, Matthias J. Wu, Ona Steup-Beekman, Gerda M. Steens, Stefan C. Huizinga, Tom W. van Buchem, Mark A. van der Grond, Jeroen TI Perfusion MRI in Neuro-Psychiatric Systemic Lupus Erthemathosus SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE perfusion MR; systemic lupus erythematosus; neuropsychiatric; immunological disorder; ischemia ID CEREBRAL-BLOOD-FLOW; EMISSION COMPUTED-TOMOGRAPHY; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; ERYTHEMATOSUS; INVOLVEMENT; BRAIN; MANIFESTATIONS; AUTOANTIBODIES; IMMUNITY AB Purpose: To use perfusion weighted MR to quantify any perfusion abnormalities and to determine their contribution to neuropsychiatric (NP) involvement in systemic lupus erythematosus (SLE). Materials and methods: We applied dynamic susceptibility contrast (DSC) perfusion MRI in 15 active NPSLE, 26 inactive NPSLE patients. and 11 control subjects. Cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) maps were reconstructed and regions of interest were compared between groups. In addition, the effect of SLE criteria, NPSLE syndromes. immunological coagulation disorder, and medication on CBF. CBV, and MTT was investigated. Results: No significant differences were found between the groups in CBF, CBV, and MTT. No significant influence of SLE criteria or NPSLE syndromes on CBF, CBV, or MTT was found. No significant influence of anti-cardiolipin antibodies, lupus anti-coagulant, the presence of anti-phospholipid syndrome (APS), or medication on CBF, CBV. or MTT was found. Conclusion: Our findings suggest CBF. CBV, and MTT in the white and the gray matter in SLE patients is not significantly different from healthy controls or between patients with and without specific symptoms or with and without immunological disorder involving coagulation. C1 [Emmer, Bart J.] Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Zuid Holland, Netherlands. [Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. RP Emmer, BJ (reprint author), Leiden Univ, Med Ctr, Dept Radiol, C2-S, NL-2300 RC Leiden, Zuid Holland, Netherlands. EM b.j.emmer@lumc.nl RI Emmer, Bart/B-3957-2012; Steens, Stefan/L-4670-2015 OI Steens, Stefan/0000-0001-8580-4726 FU Dutch Arthritis Foundation FX Contract grant sponsor: Dutch Arthritis Foundation. NR 22 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD AUG PY 2010 VL 32 IS 2 BP 283 EP 288 DI 10.1002/jmri.22251 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 632SF UT WOS:000280447300004 PM 20677252 ER PT J AU Bredella, MA Ghomi, RH Thomas, BJ Miller, KK Torriani, M AF Bredella, Miriam A. Ghomi, Reza Hosseini Thomas, Bijoy J. Miller, Karen K. Torriani, Martin TI Comparison of 3.0 T Proton Magnetic Resonance Spectroscopy Short and Long Echo-Time Measures of Intramyocellular Lipids in Obese and Normal-Weight Women SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE IMCL; 1H-MR spectroscopy; echo-time; obesity ID SKELETAL-MUSCLE; INSULIN SENSITIVITY; TRIGLYCERIDE CONTENT; BODY-FAT; QUANTIFICATION; RESISTANCE; HUMANS; LCMODEL; SPECTRA AB Purpose: To compare correlations of intramyocellular lipids (IMCL) measured by short and long echo-time proton magnetic resonance spectroscopy (1H-MRS) with indices of body composition and insulin resistance in obese and normal-weight women. Materials and Methods: We quantified IMCL of tibialis anterior (TA) and soleus (SOL) muscles in 52 premenopausal women (37 obese and 15 normal weight) using single-voxel 1H-MRS PRESS at 3.0 T with short (30 msec) and long (144 msec) echo times. Statistical analyses were performed to determine correlations of IMCL with body composition as determined by computed tomography (CT) and insulin resistance indices and to compare correlation coefficients from short and long echo-time data. Signal-to-noise ratio (SNR), linewidth, and coefficients of variation (CV) of short and long echo-time spectra were calculated. Results: Short and long echo-time IMCL from TA and SQL significantly correlated with body mass index (BMI) and abdominal fat depots (r = 0.32 to 0.70, P = <0.05), liver density (r = -0.39 to -0.50, P < 0.05), and glucose area under the curve as a measure of insulin resistance (r = 0.47 to 0.49, P < 0.05). There was no significant difference between correlation coefficients of short and long echo-time spectra (P > 0.5). Short echo-time IMCL in both muscles showed significantly higher SNR (P < 0.0001) and lower CVs when compared to long echo-time acquisitions. Linewidth measures were not significantly different between groups. Conclusion: IMCL quantification using short and long echo-time 1H-MRS at 3.0 T is useful to detect differences in muscle lipid content in obese and normal-weight subjects. In addition, IMCL correlates with body composition and markers of insulin resistance in this population with no significant difference in correlations between short and long echo-times. Short echo-time IMCL quantification of TA and SOL muscles at 3.0 T was superior to long echo-time d