FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Yano, EM Soban, LM Parkerton, PH Etzioni, DA AF Yano, Elizabeth M. Soban, Lynn M. Parkerton, Patricia H. Etzioni, David A. TI Primary care practice organization influences colorectal cancer screening performance SO HEALTH SERVICES RESEARCH LA English DT Article DE primary health care; colorectal cancer; prevention; quality of health care; veterans ID CLINICAL PREVENTIVE SERVICES; MEDICAL GROUP PRACTICES; FECAL OCCULT BLOOD; MANAGED CARE; DELIVERY SYSTEMS; QUALITY; PHYSICIANS; BARRIERS; GUIDELINES; FRAMEWORK AB Objective. To identify primary care practice characteristics associated with colorectal cancer (CRC) screening performance, controlling for patient-level factors. Data Sources/Study Setting. Primary care director survey (1999-2000) of 155 VA primary care clinics linked with 38,818 eligible patients' sociodemographics, utilization, and CRC screening experience using centralized administrative and chart-review data (2001). Study Design. Practices were characterized by degrees of centralization (e.g., authority over operations, staffing, outside-practice influence); resources (e.g., sufficiency of nonphysician staffing, space, clinical support arrangements); and complexity (e.g., facility size, academic status, managed care penetration), adjusting for patient-level covariates and contextual factors. Data Collection/Extraction Methods. Chart-based evidence of CRC screening through direct colonoscopy, sigmoidoscopy, or consecutive fecal occult blood tests, eliminating cases with documented histories of CRC, polyps, or inflammatory bowel disease. Principal Findings. After adjusting for sociodemographic characteristics and health care utilization, patients were significantly more likely to be screened for CRC if their primary care practices had greater autonomy over the internal structure of care delivery (p <.04), more clinical support arrangements (p <.03), and smaller size (p <.001). Conclusions. Deficits in primary care clinical support arrangements and local autonomy over operational management and referral procedures are associated with significantly lower CRC screening performance. Competition with hospital resource demands may impinge on the degree of internal organization of their affiliated primary care practices. C1 VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda VA Ambulatory Care Ctr, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. Univ Minnesota, Dept Colorectal Canc Surg, Minneapolis, MN USA. RP Yano, EM (reprint author), VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda VA Ambulatory Care Ctr, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 46 TC 40 Z9 43 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD JUN PY 2007 VL 42 IS 3 BP 1130 EP 1149 DI 10.1111/j.1475-6773.2006.00643.x PN 1 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 163ZG UT WOS:000246201400013 PM 17489907 ER PT J AU Mahadeva, H Mason, A Chong, N Shaw, S Samani, N AF Mahadeva, H. Mason, A. Chong, N. Shaw, S. Samani, N. TI Knockdown in zebrafish supports important role for myocyte stress 1 in cardiac development and function SO HEART LA English DT Meeting Abstract CT Annual Scientific Conference of the British-Cardiovascular-Society CY JUN 04-07, 2007 CL Glasgow, SCOTLAND SP British Cardiovasc Soc C1 Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England. Massachusetts Gen Hosp, Res Ctr, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD JUN PY 2007 VL 93 SU 1 BP A82 EP A82 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 171ND UT WOS:000246741800216 ER PT J AU Calkins, H Brugada, J Packer, DL Cappato, R Chen, SA Crijns, HJG Damiano, RJ Davies, DW Haines, DE Haissaguerre, M Iesaka, Y Jackman, W Jais, P Kottkamp, H Kuck, KH Lindsay, BD Marchlinski, FE McCarthy, PM Mont, JL Morady, F Nademanee, K Natale, A Pappone, C Prystowsky, E Raviele, A Ruskin, JN Shemin, RJ AF Calkins, Hugh Brugada, Josep Packer, Douglas L. Cappato, Riccardo Chen, Shih-Ann Crijns, Harry J. G. Damiano, Ralph J., Jr. Davies, D. Wyn Haines, David E. Haissaguerre, Michel Iesaka, Yoshito Jackman, Warren Jais, Pierre Kottkamp, Hans Kuck, Karl Heinz Lindsay, Bruce D. Marchlinski, Francis E. McCarthy, Patrick M. Mont, J. Lluis Morady, Fred Nademanee, Koontawee Natale, Andrea Pappone, Carlo Prystowsky, Eric Raviele, Antonio Ruskin, Jeremy N. Shemin, Richard J. TI HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: Recommendations for personnel, policy, procedures and follow-up SO HEART RHYTHM LA English DT Review ID PULMONARY VEIN ISOLATION; MITRAL-VALVE DISEASE; COX-MAZE PROCEDURE; PHRENIC-NERVE INJURY; ISOLATED SHEEP HEART; BIPOLAR RADIOFREQUENCY ABLATION; MAGNETIC-RESONANCE ANGIOGRAPHY; ACCESSORY ATRIOVENTRICULAR CONNECTIONS; ARRAY INTRACARDIAC ECHOCARDIOGRAPHY; EPICARDIAL MICROWAVE ABLATION C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Univ Barcelona, Hosp Clin, E-08007 Barcelona, Spain. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Arrhythmia & EP Ctr, Milan, Italy. Vet Gen Hosp, Taipei, Taiwan. Univ Hosp Maastricht, Maastricht, Netherlands. Washington Univ, Sch Med, St Louis, MO 63130 USA. St Marys Hosp, London, England. William Beaumont Hosp, Royal Oak, MI 48072 USA. Univ Bordeaux 1, Hop Cardiol, F-33405 Talence, France. Tsuchiura Kyodo Gen Hosp, Tsuchiura, Ibaraki, Japan. Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. Univ Bordeaux 1, Hop Cardiol, F-33405 Talence, France. Clin Hirslanden Zurich, Zurich, Switzerland. Allgemeines Krankenhaus St Georg, Hamburg, Germany. Washington Univ, Sch Med, St Louis, MO 63130 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Feinberg Sch Med, Chicago, IL USA. Univ Barcelona, Hosp Clin, E-08007 Barcelona, Spain. Univ Michigan Hosp, Ann Arbor, MI 48109 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Hosp San Raffaele, I-20132 Milan, Italy. Care Grp LLC, Indianapolis, IN USA. Umberto I Hosp, Venice, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Calkins, H (reprint author), Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RI Pappone, Carlo/J-9853-2016 OI Pappone, Carlo/0000-0002-0901-6135 NR 350 TC 828 Z9 862 U1 4 U2 45 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 JUN PY 2007 VL 4 IS 6 BP 816 EP 861 DI 10.1016/j.hrthm.2007.04.005 PG 46 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 178VC UT WOS:000247247200037 ER PT J AU Kulke, MH AF Kulke, Matthew H. TI Clinical presentation and management of carcinoid tumors SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID PHASE-II TRIAL; METASTATIC NEUROENDOCRINE TUMORS; RADIOLABELED SOMATOSTATIN ANALOG; ISLET CELL TUMORS; ENDOCRINE GASTROENTEROPANCREATIC TUMORS; HEPATIC ARTERIAL CHEMOEMBOLIZATION; SOUTHWEST-ONCOLOGY-GROUP; HEART-DISEASE; GASTRIC CARCINOIDS; LIVER METASTASES AB The generally indolent nature of neuroendocrine tumors is an advantage in the management of patients who have localized disease, and surgery alone is often curative. This same property presents a challenge in die treatment of patients who have metastatic disease, in whom standard cytotoxic chemotherapy has a limited benefit. In such patients, the use of somatostatin analogs, interferon, and the treatment of hepatic metastases may provide effective palliation. The highly vascular nature of carcinoid tumors has led to the investigation of antiangiogenic agents in this setting. Preliminary reports of activity associated with agents targeting the vascular endothelial growth factor pathway suggest that such strategies may play a role in the future treatment of patients who have this disease. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D 1220, Boston, MA 02114 USA. EM mkulke@partners.org FU NCI NIH HHS [K23 CA 093401]; NHLBI NIH HHS [K30 HL04095] NR 152 TC 27 Z9 29 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 2007 VL 21 IS 3 BP 433 EP + DI 10.1016/j.hoc.2007.04.004 PG 25 WC Oncology; Hematology SC Oncology; Hematology GA 184ZM UT WOS:000247681100004 PM 17548033 ER PT J AU Wertheimer, AM Polyak, SJ Leistikow, R Rosen, HR AF Wertheimer, Anne M. Polyak, Stephen J. Leistikow, Rachel Rosen, Hugo R. TI Engulfment of apoptotic cells expressing HCV proteins leads to differential chemokine expression and STAT signaling in human dendritic cells SO HEPATOLOGY LA English DT Article ID HEPATITIS-C-VIRUS; NONSTRUCTURAL 5A PROTEIN; GENE-EXPRESSION; LIVER-DISEASE; FUNCTIONAL-ANALYSIS; T-CELLS; INFECTION; INTERLEUKIN-8; INTERFERON; REPLICATION AB In the majority of cases, infection with hepatitis C virus (HCV) becomes chronic and is often associated with impaired innate and adaptive immune responses. The mechanisms underlying viral persistence and lack of protective immunity are poorly understood. Considering that dendritic cells (DCs) play critical roles in initiating and modulating immune responses, we explored the effect of HCV proteins on DC gene and protein expression, phenotype, and function. Human DCs were generated following plastic adherence of monocytes and culture with granulocyte-macrophage colony stimulating factor and interleukin-4 (IL-4) from normal subjects. Autologous nonadherent peripheral blood mononuclear cells were infected with vaccinia constructs expressing various HCV proteins (core-E1, WA, NS5B) or an irrelevant protein beta-galactosidase (beta-gal) as the control, induced to undergo apoptosis, then co-cultured with DCs. Between 2% and 10% of the genes probed in a cDNA nylon array were differentially regulated within DCs that had engulfed HCV proteins. In particular, the presence of intracellular NS5A led to increased transcriptional and protein expression of IL-8 (CXCL-8), a chemokine with proinflammatory and anti-interferon properties, and impaired interferon induction of signal transducers and activators of transcription 1 (STAT1) serine and tyrosine and STAT2 tyrosine phosphorylation. Conclusion: These data provide novel mechanisms by which HCV subverts antiviral host immunity. C1 Portland VA Med Ctr, Dept Med, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Vaccine & Gene Therapy Inst, Beaverton, OR USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Colorado, Grad Program Microbiol, Denver, CO 80202 USA. Univ Colorado, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. Univ Colorado, Integrated Program Immunol, Denver, CO 80202 USA. Univ Colorado, Hepatitis C Ctr, Denver, CO 80202 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. RP Rosen, HR (reprint author), Univ Colorado, UCHSC GI Div, 4200 E 9th Ave B-158, Denver, CO 80202 USA. EM hugo.rosen@uchsc.edu RI Polyak, Stephen/B-5743-2011 FU NCRR NIH HHS [5M01 RR 000334]; NIAID NIH HHS [U19 AI066328, U19 AI066328-030002]; NIDDK NIH HHS [DK 62187, R01 DK 060590] NR 49 TC 15 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2007 VL 45 IS 6 BP 1422 EP 1432 DI 10.1002/hep.21637 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 175KC UT WOS:000247011500014 PM 17538964 ER PT J AU Nakazawa, G Finn, AV Virmani, R AF Nakazawa, Gaku Finn, Aloke V. Virmani, Renu TI Vascular pathology of drug-eluting stents SO HERZ LA English DT Article DE stents; thrombosis; endothelium ID SERIAL INTRAVASCULAR ULTRASOUND; LONG-TERM OUTCOMES; BARE-METAL STENTS; AMERICAN-HEART-ASSOCIATION; BALLOON-EXPANDABLE-STENT; COLLEGE-OF-CARDIOLOGY; CORONARY ANGIOPLASTY; BIFURCATION LESIONS; ANTIPLATELET THERAPY; NEOINTIMAL GROWTH AB Polymer-based sirolimus- (Cypher((R))) and paclitaxeleluting stents (Taxus((R))), so-called drug-eluting stents (DES), have become the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary revascularization (PCI).While these stents have reduced rates of restenosis and late lumen loss compared to bare-metal stents (BMS), late thrombosis, a life-threatening complication of this technology, has emerged as a major concern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic samples taken after implantation of these devices. These data indicate that the DES cause substantial impairment in arterial healing characterized by lack of complete reendothelialization and persistence of fibrin when compared to BMS. This so-called delayed healing is identified as '' the primary substrate of an underlying cause of late DES thrombosis at autopsy Several additional risk factors for late stent thrombosis include penetration of necrotic core, malapposition, overlapping stent placement, excessive stent length, and bifurcation lesions. These represent additional barriers to healing and should be avoided if DES are to be used in order to minimize the late thrombotic risks of these devices. Since the time course of complete healing with DES is unknown, the optimal duration of antiplatelet treatment remains to be determined. C1 CVPath Inst Inc, Gaithersburg, MD 20878 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Virmani, R (reprint author), CVPath Inst Inc, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 45 TC 37 Z9 39 U1 0 U2 3 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0340-9937 J9 HERZ JI Herz PD JUN PY 2007 VL 32 IS 4 BP 274 EP 280 DI 10.1007/s00059-007-2997-9 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 203WN UT WOS:000249004800006 PM 17607533 ER PT J AU Luks, AM Henderson, WR Swenson, ER AF Luks, Andrew M. Henderson, William R., Jr. Swenson, Erik R. TI Leukotriene receptor blockade does not prevent acute mountain sickness induced by normobaric hypoxia SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE acute mountain sickness; high altitude; montelukast; leukotriene receptor blockade; leukotrienes; urinary leukotriene E-4 ID HIGH-ALTITUDE; E(4) LEVELS; MONTELUKAST; MODERATE; E-4 AB Luks, Andrew M., William R. Henderson, Jr., and Erik R. Swenson. Leukotriene receptor blockade does not prevent acute mountain sickness induced by normobaric hypoxia. High Alt. Med. Biol. 8:131-138, 2007.-Previous research has demonstrated that blood and urine concentrations of various leukotrienes are elevated with acute hypoxic exposure. Some of these studies have suggested that leukotrienes may be mediators in the pathogenesis of acute mountain sickness (AMS). We conducted a randomized, double-blind study to determine if AMS symptoms correlated with the increase in leukotriene synthesis and if prophylactic leukotriene receptor blockade would prevent the development of AMS in a simulated high altitude exposure. Three male and five female subjects completed two normobaric hypoxia chamber exposures (average F 102 12.4 +/- 0.09%), receiving montelukast 10 mg daily for 4 days prior to one session and placebo for 4 days prior to the other session. There were no differences in Lake Louise AMS scores, time spent in the chamber, average oxygen saturation, and average heart rate during the montelukast and placebo sessions. Headache scores were higher during treatment with montelukast than during treatment with placebo. Compared to preexposure values, urinary leukotriene E-4 concentrations were unchanged during the hypoxic chamber exposure following treatment with placebo or montelukast. Urinary leukotriene E-4 excretion during the hypoxic exposure did not differ between the two sessions. A 4-day course of leukotriene receptor blockade does not prevent symptoms of AMS. These results suggest that leukotrienes do not play a causal role in the pathophysiology of AMS. C1 Univ Washington, Div Pulm & Crit Care, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Ctr Allergy & Inflammat, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA. RP Luks, AM (reprint author), Univ Washington, Div Pulm & Crit Care, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, 1959 NE Pacific St,Box 356522, Seattle, WA 98195 USA. EM aluks@u.washington.edu NR 13 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD SUM PY 2007 VL 8 IS 2 BP 131 EP 138 DI 10.1089/ham.2007.1052 PG 8 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA 182YF UT WOS:000247539200006 PM 17584007 ER PT J AU Fagenholz, PJ Gutman, JA Murray, AF Harris, NS AF Fagenholz, Peter J. Gutman, Jonathan A. Murray, Alice F. Harris, N. Stuart TI Treatment of high altitude pulmonary edema at 4240 m in Nepal SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE altitude sickness; pulmonary edema; altitude; mountaineering; rural populations ID ACUTE MOUNTAIN-SICKNESS; EXTRAVASCULAR LUNG WATER; SUPPLEMENTAL OXYGEN; HIMALAYAS; PREVENTION; TREKKERS; PORTERS; ILLNESS; TRIAL AB Fagenholz, Peter J., Jonathan A. Gutman, Alice F. Murray, and N. Stuart Harris. Treatment of high altitude pulmonary edema at 4240 In in Nepal. High Alt. Med. Biol. 8:139-146,2007.-High altitude pulmonary edema (HAPE) is the leading cause of death from altitude illness and rapid descent is often considered a life-saving foundation of therapy. Nevertheless, in the remote settings where HAPE often occurs, immediate descent sometimes places the victim and rescuers at risk. We treated 11 patients (7 Nepalese, 4 foreigners) for HAPE at the Himalayan Rescue Association clinic in Pheriche, Nepal (4240 m), from March 3 to May 14, 2006. Ten were admitted and primarily treated there. Seven of these (6 Nepalese, I foreigner) had serious to severe HAPE (Hultgren grades 3 or 4). Bed rest, oxygen, nifedipine, and acetazolamide were used for all patients. Sildenafil and salmeterol were used in most, but not all patients. The duration of stay was 31 +/- 16 h (range 12 to 48 h). Oxygen saturation was improved at discharge (84% +/- - 1.7%) compared with admission (59% +/- 11%), as was ultrasound comet-tail score (11 +/- 4 at discharge vs. 33 +/- 8.6 at admission), a measure of pulmonary edema for which admission and discharge values were obtained in 7 patients. We conclude it is possible to treat even serious HAPE at 4240 m and discuss the significance of the predominance of Nepali patients seen in this series. C1 Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Clin 115,Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. New Royal Infirm Edinburgh, Emergency Dept, Edinburgh, Midlothian, Scotland. RP Harris, NS (reprint author), Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Clin 115,Sch Med, Boston, MA 02114 USA. EM nsharris@partners.org NR 28 TC 25 Z9 27 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1527-0297 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD SUM PY 2007 VL 8 IS 2 BP 139 EP 146 DI 10.1089/ham.2007.1055 PG 8 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA 182YF UT WOS:000247539200007 PM 17584008 ER PT J AU Rogers, J Kochunov, P Lancaster, J Shelledy, W Glahn, D Blangero, J Fox, P AF Rogers, Jeffrey Kochunov, Peter Lancaster, Jack Shelledy, Wendy Glahn, David Blangero, John Fox, Peter TI Heritability of brain volume, surface area and shape: An MRI study in an extended pedigree of baboons SO HUMAN BRAIN MAPPING LA English DT Article DE brain size; gray matter volume; cerebral surface area; primate; regional heritability; voxel based morphometry ID BIPOLAR DISORDER; LINKAGE ANALYSIS; ANATOMICAL MRI; TRAIT LOCI; SIZE; SCHIZOPHRENIA; MORPHOMETRY; EVOLUTION; GENETICS; INTELLIGENCE AB To evaluate baboons (Papio hamadryas) as a primate model for the study of the genetic control of brain size and internal structure, we performed high resolution (< 500 mu m) magnetic resonance imaging on 109 pedigreed baboons. Quantitative genetic analysis of these MR images using a variance components approach indicates that native (untransformed) brain volume exhibits significant heritability among these baboons (h(2) = 0.52, P = 0.0049), with age and sex also accounting for substantial variation. Using global spatial normalization, we transformed all images to a standard population-specific reference, and recalculated the heritability of brain volume. The transformed images generated heritability estimates of h(2) = 0.82 (P = 0.00022) for total brain volume, h(2) = 0.86 (P = 0.0006) for cerebral volume, h(2) = 0.73 (P = 0.0069) for exposed surface area of the cerebrum and h(2) = 0.67 (P = 0.01) for gray matter volume. Regional differences in the genetic effects on brain structure were calculated using a voxel-based morphometry (VBM) approach. This analysis of regional variation shows that some areas of motor cortex and the superior temporal gyrus show relatively high heritability while other regions (e.g. superior parietal cortex) exhibit lower heritability. The general pattern of regional differences is similar to that observed in previous studies of humans. The present study demonstrates that there is substantial genetic variation underlying individual variation in brain size and structure among Papio baboons, and that broad patterns of genetic influence on variation in brain structure may be similar in baboons and humans. C1 SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78227 USA. SW Natl Primate Res Ctr, San Antonio, TX 78227 USA. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX 78285 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. RP Rogers, J (reprint author), SW Fdn Biomed Res, Dept Genet, 7620 NW Loop 410, San Antonio, TX 78227 USA. EM jrogers@darwin.sfbr.org RI Lancaster, Jack/F-2994-2010; Kochunov, Peter/E-4711-2010; Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 FU NCRR NIH HHS [P51-RR013986]; NIMH NIH HHS [R01MH078111, R37MH059490] NR 42 TC 51 Z9 51 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUN PY 2007 VL 28 IS 6 BP 576 EP 583 DI 10.1002/hbm.20407 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 169YV UT WOS:000246628900012 PM 17437285 ER PT J AU Sadri-Vakili, G Bouzou, B Benn, CL Kim, MO Chawla, P Overland, RP Glajch, KE Xia, E Qiu, ZH Hersch, SM Clark, TW Yohrling, GJ Cha, JHJ AF Sadri-Vakili, Ghazaleh Bouzou, Berengere Benn, Caroline L. Kim, Mee-Ohk Chawla, Prianka Overland, Ryan P. Glajch, Kelly E. Xia, Eva Qiu, Zhihua Hersch, Steven M. Clark, Timothy W. Yohrling, George J. Cha, Jang-Ho J. TI Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models SO HUMAN MOLECULAR GENETICS LA English DT Article ID TRANSCRIPTIONAL DYSREGULATION; MOUSE MODEL; REPRESSES TRANSCRIPTION; EXPANDED POLYGLUTAMINE; TRANSGENIC MICE; STRIATAL CELLS; EXPRESSION; BRAIN; MECHANISMS; INHIBITOR AB Transcriptional dysregulation plays a major role in the pathology of Huntington's disease (HD). However, the mechanisms causing selective downregulation of genes remain unknown. Histones regulate chromatin structure and thereby control gene expression; recent studies have demonstrated a therapeutic role for histone deacetylase (HDAC) inhibitors in polyglutamine diseases. This study demonstrates that despite no change in overall acetylated histone levels, histone H3 is hypo-acetylated at promoters of downregulated genes in R6/2 mice, ST14a and STHdh cells, as demonstrated by in vivo chromatin immunoprecipitation. In addition, HDAC inhibitor treatment increases association of acetylated histones with downregulated genes and corrects mRNA abnormalities. In contrast, there is a decrease in mRNA levels in wild-type cells following treatment with a histone acetyltransferase inhibitor. Although changes in histone acetylation correlate with decreased gene expression, histone hypo-acetylation may be a late event, as no hypo-acetylation is observed in 4-week-old R6/2 mice. Nevertheless, treatment with HDAC inhibitors corrects mRNA abnormalities through modification of histone proteins and may prove to be of therapeutic value in HD. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Interdisciplinary Informat, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Johnson & Johnson Pharmaceut, Res & Dev LLC, Spring House, PA 19477 USA. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, B114-2000,114 16th St, Charlestown, MA 02129 USA. EM cha@helix.mgh.harvard.edu OI Clark, Timothy/0000-0003-4060-7360 FU NINDS NIH HHS [NS045242, NS045806, NS38106] NR 48 TC 118 Z9 119 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2007 VL 16 IS 11 BP 1293 EP 1306 DI 10.1093/hmg/ddm078 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 190IU UT WOS:000248053300003 PM 17409194 ER PT J AU Hocker, T Tsao, HS AF Hocker, Thomas Tsao, Hensin TI Ultraviolet radiation and melanoma: A systematic review and analysis of reported sequence variants SO HUMAN MUTATION LA English DT Review DE mutation; meta-analysis; melanoma; cancer ID BRAF MUTATIONS; CANCER; DATABASE; CELLS AB Despite the large body of mutational data available for melanoma and epidemiological studies linking this cancer to ultraviolet radiation (UVR), the fundamental carcinogenic mechanisms involved in melanoma remain largely unknown. To this end, we systematically reviewed, extracted, and analyzed mutational data from the extant melanoma literature in an effort to gain more insight into its early pathogenic events. We searched PubMed (1966-january 2006) using the words "mutation" AND "melanoma" in the title or abstract. Out of 2,095 returned results, there were 203 eligible studies that were subsequently analyzed. We cataloged 8,201 somatic and cultured melanoma specimens and annotated 2,041 reported somatic sequence variants. The single BRAF c. I 799T > A (p.Val600Glu) alteration is the most prevalent variant while other A:T > T:A transversions were uncommon. Four highly-recurrent, non-ultraviolet B (UVB) changes account for most of the NRAS and BRA-F variants. CDKN2A, PTEN/MMAC1, and TP53 harbored statistically higher rates of UVB signature changes (64.2%, 52.4%, and 69.2%, respectively) than oncogenic loci (NRAS: 15.3% and BRAF: 2.4%). More specifically, cutaneous melanomas showed a significantly higher proportion of UVB signature mutations at both TP53 and CDKN2A when compared to non-skin cancers using data from their respective locus-specific databases. Superficial spreading and nodular melanomas had the highest rates of BRAF (53.4%) and NRAS (28.0%) mutations. In melanoma, there is sufficient mutational evidence to support a role for direct UVB participation, especially at TP53 and CDKN2A. For oncogenes, the role for UVB is less clear since functionally, activating changes are uncommon and are subject to sequence constraints. C1 Massachusetts Gen Hosp, Dept Dermatol, Ctr Canc, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tsao, HS (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Ctr Canc, Wellman Ctr Photomed, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 22 TC 127 Z9 130 U1 1 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JUN PY 2007 VL 28 IS 6 BP 578 EP 588 DI 10.1002/humu.20481 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 164DH UT WOS:000246212800006 PM 17295241 ER PT J AU Kanda, A Friedman, JS Nishiguchi, KM Swaroop, A AF Kanda, Atsuhiro Friedman, James S. Nishiguchi, Koji M. Swaroop, Anand TI Retinopathy mutations in the bZIP protein NRL alter phosphorylation and transcriptional activity SO HUMAN MUTATION LA English DT Article DE gene regulation; retinal degeneration; photoreceptor; transcription factor; phosphorylation; gene expression; DNA binding; rhodopsin; neural retina leucine zipper; NRL; retinal development ID DOMINANT RETINITIS-PIGMENTOSA; NUCLEAR RECEPTOR GENE; NRL(-/-) MOUSE RETINA; S-CONE SYNDROME; MOLECULAR-GENETICS; FUNCTIONAL-ANALYSIS; LEUCINE-ZIPPER; RHODOPSIN GENE; ROD PHOTORECEPTORS; SUBUNIT GENE AB The transcription factor neural retina leucine zipper (NRL) is required for rod photoreceptor differentiation during mammalian retinal development. NRL interacts with CRX, NR2E3, and other transcription factors and synergistically regulates the activity of photoreceptors-specific genes. Mutations in the human NRL gene are associated with retinal degenerative diseases. Here we report functional analyses of 17 amino acid variations and/or mutations of NRL. We show that 13 of these lead to changes in NRL phosphorylation. Six mutations at residues p.S50 (c.148T > A, c.148T > C, and c-149C > T) and p.P51 (c.151C > A, c.151C > T, and c.152C > T), identified in patients with autosomal dominant retinitis pigmentosa, result in a major NRL isoform that exhibits reduced phosphorylation but enhanced activation of the rhodopsin promoter. The truncated NRL mutant proteins-p.L75fs (c.224_225insC) and p.L160fs (c.459_477dup)-do not localize to the nucleus because of the absence of bZIP domain. The p.L160P (c.479T > C), p.L160fs, and p.R218fs (c.654delC) mutant proteins do not bind to the NRL,response element, as revealed by electrophoretic mobility shift assays. These three and p.S225N (c.674G > A) mutant show reduced transcriptional activity and may contribute to recessive disease. The p.P67S (c. 199C > T) and p.L235F (c.703C > T) variations in NRL do not appear to directly cause retinitis pigmentosa, while p.E63K (c.187G > A), p.A76V (c.227C > T), p.G122E (c.365G > A), and p.H125Q (c.375C > G) are of uncertain significance. Our results support the notion that gain of-function mutations in the NRL gene cause autosomal dominant retinitis pigmentosa while loss-of-function NRL mutations lead to autosomal recessive retinitis pigmentosa. We propose that differential phosphorylation of NRL fine,tunes its transcriptional regulatory activity, leading to a more precise control of gene expression. C1 Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02115 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Swaroop, A (reprint author), Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA. EM swaroop@umich.edu OI Swaroop, Anand/0000-0002-1975-1141 FU NEI NIH HHS [EY07003, EY11115] NR 47 TC 20 Z9 20 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JUN PY 2007 VL 28 IS 6 BP 589 EP 598 DI 10.1002/humu.20488 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 164DH UT WOS:000246212800007 PM 17335001 ER PT J AU Ogino, S Kawasaki, T Ogawa, A Kirkner, GJ Loda, M Fuchs, CS AF Ogino, Shuji Kawasaki, Takako Ogawa, Akiyo Kirkner, Gregory J. Loda, Massimo Fuchs, Charles S. TI Fatty acid synthase overexpression in colorectal cancer is associated with microsatellite instability, independent of CpG island methylator phenotype SO HUMAN PATHOLOGY LA English DT Article DE colon cancer; FASN; MSI; CIMP; DNA methylation ID COLON-CANCER; PHYSICAL-ACTIVITY; BREAST-CARCINOMA; PROSTATE-CANCER; EXPRESSION; CIMP; RISK; FAS; MUTATION; FEATURES AB Overexpression of fatty acid synthase (FASN), a key enzyme for de novo lipogenesis, is observed in many cancers including colorectal cancer and is associated with poor clinical outcomes. Cellular FASN expression is physiologically upregulated in a state of energy excess. Obesity and excess energy balance have been known to be risk factors for colorectal cancer. High degree of microsatellite instability (MSI-H) is a distinct phenotype in colorectal cancer, associated with CpG island methylator phenotype (CIMP). Previous data suggest that obesity or altered energy balance may potentially modify risks for MSI-H cancers and microsatellite stable (MSS) cancers differently. However, the relationship between MSI and FASN overexpression has not been investigated. Using 976 cases of population-based colorectal cancer samples from 2 large prospective cohort studies, we correlated FASN expression (by immunohistochemistry) with MSI, KRAS and BRAF mutations, p53 expression (by immunohistochemistry), and CIMP status [determined by MethyLight for 8 CIMP-specific gene promoters including CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1]. Marked (2+) FASN overexpression was observed in 110 (11%) of the 976 tumors and was significantly more common in MSI-H tumors (21% [28/135]) than MSI-low (5.6% [4/72], P = .004) and MSS tumors (11% [72/678], P = .001). The association between FASN overexpression and MSI-H persisted even after stratification by CIMP status. In contrast, FASN overexpression was not correlated with CIMP after stratification by MSI status. Fatty acid synthase overexpression was not significantly correlated with sex, tumor location, p53, or KRAS/BRAF status. In conclusion, FASN overexpression in colorectal cancer is associated with MSI-H, independent of CIMP status. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA55075-13, P01 CA87969-03] NR 35 TC 29 Z9 31 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUN PY 2007 VL 38 IS 6 BP 842 EP 849 DI 10.1016/j.humpath.2006.11.018 PG 8 WC Pathology SC Pathology GA 172OV UT WOS:000246814500004 PM 17350669 ER PT J AU Stachurski, D Miron, PM Al-Homsi, S Hutchinson, L Harris, NL Woda, B Wang, SA AF Stachurski, Dariusz Miron, Patricia Minehart Al-Homsi, Samer Hutchinson, Lloyd Harris, Nancy Lee Woda, Bruce Wang, Sa A. TI Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma with a complex karyotype and cryptic 3 ' ALK gene insertion to chromosome 4 q22-24 SO HUMAN PATHOLOGY LA English DT Article DE ALK; diffuse large B-cell lymphoma; cytogenetics; fluorescence in situ; hybridization (FISH); 4q22-24 ID TRANSLOCATION; FUSION AB Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare tumor that is frequently associated with t(2;17)(p23;q23), a translocation fusing the ALK gene at 2p23 to the clathrin heavy chain gene (CLTC) at 17q23. Here, we report a unique case of ALK-positive DLBCL with plasmablastic morphology and focal cytoplasmic granular ALK stain in an HIV-negative 33-year-old man. By conventional karyotyping, the lymphoma cells were near-tetraploid and included 4 structurally normal copies each of chromosomes 2 and 17. Fluorescence in situ hybridization revealed an apparently normal, intact ALK gene on each of the 4 chromosome 2 homologs plus a cytogenetically cryptic ALK gene insertion into 2 of the 4 chromosome 4 homologs at band 4q22-24. The lymphoma cells expressed CD138, lambda light chain, focal and weak CD30, and exhibited aberrant T-cell antigens, including perform. This case indicates that ALK-positive DLBCL is more heterogeneous at the cytogenetic/molecular level than previously recognized. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA 01605 USA. Univ Massachusetts, Med Ctr, Dept Internal Med, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Wang, SA (reprint author), Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA 01605 USA. EM wanga@ummhc.org NR 14 TC 30 Z9 35 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUN PY 2007 VL 38 IS 6 BP 940 EP 945 DI 10.1016/j.humpath.2006.12.019 PG 6 WC Pathology SC Pathology GA 172OV UT WOS:000246814500016 PM 17509395 ER PT J AU Lock, RL Szeto, TH Entwistle, A Gjoerup, OV Jat, PS AF Lock, Rowena L. Szeto, Tim H. Entwistle, Alan Gjoerup, Ole V. Jat, Parmjit S. TI Preparation of monoclonal antibodies against the spindle checkpoint kinase Bub1 SO HYBRIDOMA LA English DT Article ID KINETOCHORE LOCALIZATION; MITOTIC CHECKPOINT; PROTEIN BUB1; CENP-E; PHOSPHORYLATION; CHROMOSOMES; INSTABILITY; MITOSIS; CANCER; GENES AB The Bub1 kinase is a critical component of the spindle checkpoint involved in monitoring the separation of sister chromatids at mitosis. The viral oncoprotein Simian virus 40 large T antigen (LT) can bind and perturb the spindle checkpoint function of Bub1. We have developed three highly specific monoclonal antibodies against the Bub1 protein and have demonstrated that they can all detect Bub1 via Western blotting and immunofluorescence, in addition to their ability to immunoprecipitate Bub1. C1 UCL, Dept Neurodegenerat Dis, Inst Neurol, London W1CN 3BG, England. Royal Free & Univ Coll Sch Med, Ludwig Inst Canc Res, London, England. UCL, Dept Biochem & Mol Biol, London W1CN 3BG, England. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Jat, PS (reprint author), UCL, Dept Neurodegenerat Dis, Inst Neurol, Queen Sq, London W1CN 3BG, England. EM p.jat@prion.ucl.ac.uk FU Wellcome Trust NR 21 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1554-0014 J9 HYBRIDOMA JI Hybridoma PD JUN PY 2007 VL 26 IS 3 BP 140 EP 147 DI 10.1089/hyb.2007.003 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA 184CT UT WOS:000247619400003 PM 17600495 ER PT J AU Mitchell, GF Guo, CY Kathiresan, S Vasan, RS Larson, MG Vita, JA Keyes, MJ Vyas, M Newton-Cheh, C Musone, SL Camargo, AL Drake, JA Levy, D O'Donnell, CJ Hirschhorn, JN Benjamin, EJ AF Mitchell, Gary F. Guo, Chao-Yu Kathiresan, Sekar Vasan, Ramachandran S. Larson, Martin G. Vita, Joseph A. Keyes, Michelle J. Vyas, Mitul Newton-Cheh, Christopher Musone, Stacy L. Camargo, Amy L. Drake, Jared A. Levy, Daniel O'Donnell, Christopher J. Hirschhorn, Joel N. Benjamin, Emelia J. TI Vascular stiffness and genetic variation at the endothelial nitric oxide synthase locus - The Framingham Heart Study SO HYPERTENSION LA English DT Article DE single nucleotide polymorphism; nitric oxide synthase; pulse pressure; medical genetics; epidemiology ID BLOOD-PRESSURE; ARTERIAL STIFFNESS; ESSENTIAL-HYPERTENSION; AORTIC STIFFNESS; WAVE REFLECTION; IN-VIVO; POLYMORPHISM; DISTENSIBILITY; CLEAVAGE; GLU(298) AB Arterial stiffness is a moderately heritable trait that is affected by alterations in the bioavailability of NO. Previous studies have found associations between variants in the gene for endothelial NO synthase (NOS3) and arterial properties. We previously identified a linkage peak for forward pressure wave amplitude in the immediate vicinity of NOS3. Therefore, we evaluated relations between arterial stiffness measures and common genetic variants at this locus. Eighteen single nucleotide polymorphisms capturing approximate to 90% of underlying common variation in NOS3 were genotyped in unrelated Framingham Heart Study participants (N = 1157; 52.2% women; mean age: 62 years) with routinely ascertained tonometry data that provided 5 arterial phenotypes (forward and reflected pressure wave amplitude, central pulse pressure, carotid - femoral pulse wave velocity, and mean arterial pressure). In women but not men, the genotype for the common NOS3 missense mutation (Glu298Asp, rs1799983) was related to central pulse pressure (women: GG = 53 +/- 0.9, GT = 54 +/- 0.9, and TT = 47 +/- 2.0 mm Hg, P = 0.0047; men: GG = 50 +/- 1.0, GT = 49 +/- 0.9, and TT = 47 +/- 1.8 mm Hg, P = 0.30) and forward wave amplitude (women: GG = 41 +/- 0.7, GT = 42 +/- 0.7, and TT = 38 +/- 1.6 mm Hg, P = 0.029; men: GG = 42 +/- 0.9, GT = 41 +/- 0.8, and TT = 39 +/- 1.5 mm Hg, P = 0.47). The only other nominally significant sex-specific association in men but not women was between an intronic polymorphism (rs1800781) and reflected wave amplitude (women: AA = 10.4 +/- 0.4, AG = 11.1 +/- 0.6, and GG = 8.9 +/- 2.2 mm Hg, P = 0.50; men: AA = 6.1 +/- 0.3, AG = 7.3 +/- 0.5, and GG = 11.3 +/- 2.3 mm Hg, P = 0.014). After adjusting for multiple testing (18 polymorphisms and 5 phenotypes), these nominal associations were no longer significant. The present study was suggestive of modest relations between common genetic variants at the NOS3 locus and arterial stiffness. C1 Cardiovasc Engn Inc, Waltham, MA 02453 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. MIT, Program Med & Populat Genet, Cambridge, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Mitchell, GF (reprint author), Cardiovasc Engn Inc, 51 Sawyer Rd,Suite 100, Waltham, MA 02453 USA. EM GaryFMitchell@mindspring.com OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [HL60040, HL66582, HL70100, HL71039, K24-HL-04334, N01-HC-25195, N01-HV28178] NR 25 TC 20 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2007 VL 49 IS 6 BP 1285 EP 1290 DI 10.1161/HYPERTENSIONAHA.106.085266 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171FN UT WOS:000246720800021 PM 17404185 ER PT J AU Mehta, SK Rame, JE Khera, A Murphy, SA Canham, RM Peshock, RM de Lemos, JA Drazner, MH AF Mehta, Sameer K. Rame, J. Eduardo Khera, Amit Murphy, Sabina A. Canham, Russell M. Peshock, Ronald M. de Lemos, James A. Drazner, Mark H. TI Left ventricular hypertrophy, subclinical atherosclerosis, and inflammation SO HYPERTENSION LA English DT Article DE left ventricular hypertrophy; atherosclerosis; inflammation; myocardial infarction; coronary artery disease ID CORONARY-ARTERY CALCIUM; C-REACTIVE PROTEIN; ULTRAFAST COMPUTED-TOMOGRAPHY; ESSENTIAL-HYPERTENSION; HEART-DISEASE; SYSTEMIC HYPERTENSION; CARDIAC-HYPERTROPHY; AFRICAN-AMERICANS; PROGNOSTIC IMPLICATIONS; MYOCARDIAL-INFARCTION AB To elucidate mechanisms by which left ventricular (LV) hypertrophy (LVH) increases the risk of atherosclerotic heart disease, we sought to determine whether LVH is independently associated with coronary artery calcium (CAC) and serum C-reactive protein (CRP) levels in the general population. The Dallas Heart Study is a population-based sample in which 2633 individuals underwent cardiac MRI to measure LV structure, electron beam CT to measure CAC, and measurement of plasma CRP. We used univariate and multivariable analyses to determine whether LV mass and markers of concentric LV hypertrophy or dilation were associated with CAC and CRP. Increasing quartiles of LV mass indexed to fat-free mass, LV wall thickness, and concentricity, but not LV volume, were associated with CAC in both men and women (P < 0.001). After adjustment for traditional cardiovascular risk factors and statin use, LV wall thickness and concentricity remained associated with CAC in linear regression (P < 0.001 for each). These associations were particularly robust in blacks. LV wall thickness and concentricity were also associated with elevated CRP levels (P < 0.001 for both) in gender-stratified univariate analyses, although these associations did not persist in multivariable analysis. In conclusion, concentric LVH is an independent risk factor for subclinical atherosclerosis. LVH is also associated with an inflammatory state as reflected in elevated CRP levels, although this relationship appears to be mediated by comorbid conditions. These data likely explain in part why individuals with LVH are at increased risk for myocardial infarction. C1 Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Div Cardiol, Dept Internal Med, Dallas, TX 75390 USA. TIMI Study Grp, Boston, MA USA. RP Drazner, MH (reprint author), Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Mark.Drazner@UTSouthwestern.edu NR 56 TC 37 Z9 43 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2007 VL 49 IS 6 BP 1385 EP 1391 DI 10.1161/HYPERTENSIONAHA.107.087890 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171FN UT WOS:000246720800035 PM 17404181 ER PT J AU Li, HL She, ZG Li, TB Wang, AB Yang, QL Wei, YS Wang, YG Liu, DP AF Li, Hong-Liang She, Zhi-Gang Li, Tian-Bo Wang, Ai-Bing Yang, Qinglin Wei, Yu-Sheng Wang, Yi-Guang Liu, De-Pei TI Overexpression of myofibrillogenesis regulator-1 aggravates cardiac hypertrophy induced by angiotensin II in mice SO HYPERTENSION LA English DT Article DE hypertrophy; myocardium; NF-kappa B; myofibrillogenesis regulator-1; fibrosis; angiotensin II ID NF-KAPPA-B; END-ORGAN DAMAGE; HEART-FAILURE; RAT-HEART; ACTIVATION; MECHANISM; PATHWAYS; RENIN; INFLAMMATION; DYSFUNCTION AB Myofibrillogenesis regulator-1 (MR-1) augments cardiomyocytes hypertrophy induced by angiotensin II (Ang II) in vitro. However, its roles in cardiac hypertrophy in vivo remain unknown. Here, we investigate whether MR-1 can promote cardiac hypertrophy induced by Ang II in vivo and elucidate the molecular mechanisms of MR-1 on cardiac hypertrophy. We used a model of Ang II-induced cardiac hypertrophy by infusion of Ang II in female mice. In wild-type mice subjected to the Ang II infusion, cardiac hypertrophy developed after 2 weeks. In mice overexpressing human MR-1 (transgenic), however, cardiac hypertrophy was significantly greater than in wild-type mice as estimated by heart weight: body weight ratio, cardiomyocyte area, and echocardiographic measurements, as well as cardiac atrial natriuretic peptide and B-type natriuretic peptide mRNA and protein levels. Our further results showed that cardiac inflammation and fibrosis observed in wild-type Ang II mice were augmented in transgenic Ang II mice. Importantly, increased nuclear factor kappa B activation was significantly increased higher in transgenic mice compared with wild-type mice after 2 weeks of Ang II infusion. In vitro experiments also revealed that overexpression of MR-1 enhanced Ang II-induced nuclear factor kappa B activation, whereas downregulation of MR-1 blocked it in cardiac myocytes. In conclusion, our results suggest that MR-1 plays an aggravative role in the development of cardiac hypertrophy via activation of the nuclear factor kappa B signaling pathway. C1 Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100005, Peoples R China. Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100005, Peoples R China. Peking Union Med Coll, Beijing, Peoples R China. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Mrehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA USA. RP Liu, DP (reprint author), Chinese Acad Med Sci, Natl Lab Med Mol Biol, Inst Basic Med Sci, Beijing 100005, Peoples R China. EM wangyh456@yahoo.com.cn; liudp@pumc.edu.cn RI Li, Tianbo/C-6118-2012 NR 28 TC 39 Z9 45 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2007 VL 49 IS 6 BP 1399 EP 1408 DI 10.1161/HYPERTENSIONAHA.106.085399 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171FN UT WOS:000246720800037 PM 17420335 ER PT J AU Duda, DG AF Duda, Dan G. TI Angiogenesis and anti-angiogenesis in cancer SO IDRUGS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Duda, DG (reprint author), Massachusetts Gen Hosp, Cox 734,100 Blossom St, Boston, MA 02114 USA. EM duda@steele.mgh.harvard.edu NR 0 TC 3 Z9 3 U1 0 U2 0 PU THOMSON SCIENTIFIC PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND STREET, LONDON, W1T 4JE, ENGLAND SN 1369-7056 J9 IDRUGS JI IDrugs PD JUN PY 2007 VL 10 IS 6 BP 366 EP 369 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 178VD UT WOS:000247247300005 PM 17641996 ER PT J AU Merfeld, DM Haburcakova, C Gong, W Lewis, RF AF Merfeld, Daniel M. Haburcakova, Csilla Gong, Wangsong Lewis, Richard F. TI Chronic vestibulo-ocular reflexes evoked by a vestibular prosthesis SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE adaptation; habituation; plasticity; VOR ID SEMICIRCULAR CANAL PROSTHESIS; COCHLEAR IMPLANTS; SQUIRREL-MONKEY; STIMULATION; PERFORMANCE; ADAPTATION; AFFERENTS; SYSTEM; CELLS; MODEL AB We are developing prosthetics for patients suffering from peripheral vestibular dysfunction. We tested a sensory-replacement prosthesis that stimulates neurons innervating the vestibular system by providing chronic pulsatile stimulation to electrodes placed in monkeys' lateral semicircular canals, which were plugged bilaterally, and used head angular velocity to modulate the current pulse rate. As an encouraging finding, we observed vestibulo-ocular reflexes that continued to be evoked by the motion-modulated stimulation months after the nystagmus evoked by the constant-rate baseline stimulation had dissipated. This suggests that long-term functional replacement of absent vestibular function is feasible. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu FU NIDCD NIH HHS [R01 DC-03066] NR 27 TC 56 Z9 58 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 EI 1558-2531 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUN PY 2007 VL 54 IS 6 BP 1005 EP 1015 DI 10.1109/TBME.2007.891943 PN 1 PG 11 WC Engineering, Biomedical SC Engineering GA 172RK UT WOS:000246821500006 PM 17554820 ER PT J AU Bhandoola, A von Boehmer, H Petrie, HT Zuniga-Pflucker, JC AF Bhandoola, Avinash von Boehmer, Harald Petrie, Howard T. Zuniga-Pfluecker, Juan Carlos TI Commitment and developmental potential of extrathymic and intrathymic T cell precursors: Plenty to choose from SO IMMUNITY LA English DT Review ID MOUSE BONE-MARROW; MULTIPOTENT HEMATOPOIETIC PROGENITORS; COMMON LYMPHOID PROGENITORS; BETA-SELECTION CHECKPOINT; MURINE FETAL BLOOD; LINEAGE COMMITMENT; STEM-CELLS; ALPHA-BETA; C-KIT; THYMIC MICROENVIRONMENT AB T cells developing in the thymus are derived from hematopoietic stem cells (HSCs) in the bone marrow (BM). Understanding the developmental steps linking multipotent HSCs to intrathymic T lineage-committed progenitors is important for understanding cancer in T lineage cells, improving T cell reconstitution after BM transplantation, and designing gene-therapy approaches to treat defective T cell development or function. Such an understanding may also help ameliorate immunological defects in aging. This review covers the differentiation steps between HSCs and committed T cell progenitors within the thymus. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Scripps Florida Res Inst, Jupiter, FL 33458 USA. Univ Toronto, Dept Immunol, Toronto, ON M4N 3M5, Canada. Sunnybrook Res Inst, Toronto, ON M4N 3M5, Canada. RP Bhandoola, A (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. EM bhandooa@mail.med.upenn.edu; harald_von_boehmer@dfci.harvard.edu; hpetrie@scripps.edu; jczp@sri.utoronto.ca RI Zuniga-Pflucker, Juan/H-1295-2012; OI Zuniga-Pflucker, Juan Carlos/0000-0003-2538-3178 NR 104 TC 160 Z9 161 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2007 VL 26 IS 6 BP 678 EP 689 DI 10.1016/j.immuni.2007.05.009 PG 12 WC Immunology SC Immunology GA 184MX UT WOS:000247646900003 PM 17582341 ER PT J AU Iwasaki, H Akashi, K AF Iwasaki, Hirorni Akashi, Koichi TI Myeloid lineage commitment from the hematopoietic stem cell SO IMMUNITY LA English DT Review ID TRANSCRIPTION FACTOR GATA-1; COLONY-STIMULATING FACTOR; RECEPTOR-DEFICIENT MICE; COMMON LYMPHOID PROGENITORS; GREEN FLUORESCENT PROTEIN; SELF-RENEWAL CAPACITY; NATURAL-KILLER-CELLS; DENDRITIC CELLS; BONE-MARROW; LONG-TERM AB Prospective isolation of hematopoietic stem and progenitor cells has identified the lineal relationships among all blood-cell types and has allowed their developmental mechanisms to be assayed at the single-cell level. These isolated cell populations are used to elucidate the molecular mechanism of lineage fate decision and of its plasticity directly by stage-specific enforcement or repression of lineage-instructive signaling in purified cells. With an emphasis on the myeloid lineage, this review summarizes current concepts and controversies regarding adult murine hematopoietic development and discusses the potential mechanisms, operated by single or by multiple transcription factors, of myeloid lineage fate decision. C1 Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Akashi, K (reprint author), Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. EM koichi_akashi@dfci.harvard.edu RI U-ID, Kyushu/C-5291-2016 NR 122 TC 184 Z9 190 U1 2 U2 24 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2007 VL 26 IS 6 BP 726 EP 740 DI 10.1016/j.immuni.2007.06.004 PG 15 WC Immunology SC Immunology GA 184MX UT WOS:000247646900007 PM 17582345 ER PT J AU Carman, CV Sage, PT Sciuto, TE de la Fuente, MA Geha, RS Ochs, HD Dvorak, HF Dvorak, AM Springer, TA AF Carman, Christopher V. Sage, Peter T. Sciuto, Tracey E. de la Fuente, Miguel A. Geha, Raif S. Ochs, Hans D. Dvorak, Harold F. Dvorak, Ann M. Springer, Timothy A. TI Transcellular diapedesis is initiated by invasive podosomes SO IMMUNITY LA English DT Article ID ENDOTHELIAL-CELLS; LYMPHOCYTE MIGRATION; NEUTROPHIL MIGRATION; SYNDROME PROTEIN; ADHESION; VENULES; ICAM-1; SIGNALS; PATHWAY; PATHOGENESIS AB Diapedesis is critical for immune system function and inflammatory responses. This occurs by migration of blood leukocytes either directly through individual microvascular endothelial cells (the "transcellular" route) or between them (the "paracellular" route). Mechanisms for transcellular pore formation in endothelium remain unknown. Here we demonstrate that lymphocytes used podosomes and extended "invasive podosomes" to palpate the surface of, and ultimately form transcellular pores through, the endothelium. In lymphocytes, these structures were dependent on Src kinase and the actin regulatory protein WASP; inhibition of podosome formation selectively blocked the transcellular route of diapedesis. In endothelium, membrane fusion events dependent on the SNARE-containing membrane fusion complex and intracellular calcium were required for efficient transcellular pore formation in response to podosomes. These findings provide insights into basic mechanisms for leukocyte trafficking and the functions of podosomes. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. EM springer@cbr.med.harvard.edu RI de la Fuente, Miiguel /C-7478-2013; Carman, Christopher/L-8108-2016 OI de la Fuente, Miiguel /0000-0003-4619-8756; Carman, Christopher/0000-0001-7358-2548 FU NCI NIH HHS [R37 CA031798-27, R37 CA031798] NR 40 TC 282 Z9 290 U1 3 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2007 VL 26 IS 6 BP 784 EP 797 DI 10.1016/j.immuni.2007.04.015 PG 14 WC Immunology SC Immunology GA 184MX UT WOS:000247646900014 PM 17570692 ER PT J AU Ghose, C Kalsy, A Sheikh, A Rollenhagen, J John, M Young, J Rollins, SM Qadri, F Calderwood, SB Kelly, CP Ryan, ET AF Ghose, Chandrabali Kalsy, Anuj Sheikh, Alaullah Rollenhagen, Julianne John, Manohar Young, John Rollins, Sean M. Qadri, FIrdausi Calderwood, Stephen B. Kelly, Ciaran P. Ryan, Edward T. TI Transcutaneous immunization with Clostridium difficile toxoid A induces systemic and mucosal immune responses and toxin A-neutralizing antibodies in mice SO INFECTION AND IMMUNITY LA English DT Article ID ENTEROTOXIGENIC ESCHERICHIA-COLI; ADP-RIBOSYLATING EXOTOXINS; HEAT-LABILE ENTEROTOXIN; PROTECTIVE IMMUNITY; VIBRIO-CHOLERAE; HOSPITAL ENVIRONMENT; ORAL IMMUNIZATION; DISEASE; INFECTION; DIARRHEA AB Clostridium difficile is the leading cause of nosocomial infectious diarrhea. C difficile produces two toxins (A and B), and systemic and mucosal anti-toxin A antibodies prevent or limit C difficile-associated diarrhea. To evaluate whether transcutaneous immunization with formalin-treated C difficile toxin A (CDA) induces systemic and mucosal anti-CDA immune responses, we transcutaneously immunized three cohorts of mice with CDA with or without immunoadjuvantative cholera toxin (CT) on days 0, 14, 28, and 42. Mice transcutaneously immunized with CDA and CT developed prominent anti-CDA and anti-CT immunoglobulin G (IgG) and IgA responses in serum and anti-CDA and anti-CT IgA responses in stool. Sera from immunized mice were able to neutralize C. difficile toxin A activity in an in vitro cell culture assay. CDA itself demonstrated adjuvant activity and enhanced both serum and stool anti-CT IgA responses. Our results suggest that transcutaneous immunization with CDA toxoid may be a feasible immunization strategy against C. difficile, an important cause of morbidity and mortality against which current preventative strategies are failing. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. ICDDR, B Ctr Hlth & Populat Studies, Dhaka, Bangladesh. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM etryan@partners.org OI Rollins, Sean/0000-0002-3724-1989 FU FIC NIH HHS [D43 TW005572, D43 TW 05572]; NIAID NIH HHS [AI 53069, U54 AI057159, U54 AI 057159, R01 AI040725, AI 40725, R01 AI053069] NR 58 TC 36 Z9 39 U1 0 U2 1 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 JUN PY 2007 VL 75 IS 6 BP 2826 EP 2832 DI 10.1128/IAI.00127-07 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 172SN UT WOS:000246824500020 PM 17371854 ER PT J AU Matsunaga, J Lo, M Bulach, DM Zuerner, RL Adler, B Haake, DA AF Matsunaga, James Lo, Miranda Bulach, Dieter M. Zuerner, Richard L. Adler, Ben Haake, David A. TI Response of Leptospira interrogans to physiologic osmolarity: Relevance in signaling the environment-to-host transition SO INFECTION AND IMMUNITY LA English DT Article ID SURFACE-EXPOSED LIPOPROTEIN; OSMOTIC-STRESS RESPONSE; OUTER-MEMBRANE PROTEINS; PATHOGENIC LEPTOSPIRA; GENE-EXPRESSION; SEROVAR LAI; MOLECULAR CHARACTERIZATION; MAMMALIAN INFECTION; ESCHERICHIA-COLI; CYCLIC-AMP AB Transmission of pathogenic Leptospira between mammalian hosts usually involves dissemination via soil or water contaminated by the urine of carrier animals. The ability of Leptospira to adapt to the diverse conditions found inside and outside the host is reflected in its relatively large genome size and high percentage of signal transduction genes. An exception is Leptospira borgpetersenii serovar Hardjo, which is transmitted by direct contact and appears to have lost genes necessary for survival outside the mammalian host. Invasion of host tissues by Leptospira interrogans involves a transition from a low osmolar environment outside the host to a higher physiologic osmolar environment within the host. Expression of the lipoprotein LigA and LigB adhesins is strongly induced by an upshift in osmolarity to the level found in mammalian host tissues. These data suggest that Leptospira utilizes changes in osmolarity to regulate virulence characteristics. To better understand how L. interrogans serovar Copenhageni adapts to osmolar conditions that correspond with invasion of a mammalian host, we quantified alterations in transcript levels using whole-genome microarrays. Overnight exposure in leptospiral culture medium supplemented with sodium chloride to physiologic osmolarity significantly altered the transcript levels of 6% of L. interrogans genes. Repressed genes were significantly more likely to be absent or pseudogenes in L. borgpetersenii, suggesting that osmolarity is relevant in studying the adaptation of L. interrogans to host conditions. Genes induced by physiologic osmolarity encoded a higher than expected number of proteins involved in signal transduction. Further, genes predicted to encode lipoproteins and those coregulated by temperature were overrepresented among both salt-induced and salt-repressed genes. In contrast, leptospiral homologues of hyperosmotic or general stress genes were not induced at physiologic osmolarity. These findings suggest that physiologic osmolarity is an important signal for regulation of gene expression by pathogenic leptospires during transition from ambient conditions to the host tissue environment. C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Monash Univ, Australian Bacterial Pathogenesis Program, Clayton, Vic 3800, Australia. Monash Univ, Victorian Bioinformat Consortium, Clayton, Vic 3800, Australia. USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA. Monash Univ, Australian Res Council Ctr Excellence Struct & Fu, Clayton, Vic 3800, Australia. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. RP Matsunaga, J (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, Mail Code 151, Los Angeles, CA 90073 USA. EM jamesm@ucla.edu RI Bulach, Dieter/D-5793-2011 OI Bulach, Dieter/0000-0001-9823-6078 FU NIAID NIH HHS [R01 AI034431, R01 AI034431-10A1, R21 AI034431, R29 AI034431, AI 34431] NR 62 TC 63 Z9 64 U1 0 U2 0 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 JUN PY 2007 VL 75 IS 6 BP 2864 EP 2874 DI 10.1128/IAI.01619-06 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 172SN UT WOS:000246824500024 PM 17371863 ER PT J AU Tager, A LaCamera, P Shea, B Campanella, G Karimi-Shah, B Kim, N Zhao, Z Polosukhin, V Xu, Y Blackwell, T Chun, J Luster, A AF Tager, A. LaCamera, P. Shea, B. Campanella, G. Karimi-Shah, B. Kim, N. Zhao, Z. Polosukhin, V. Xu, Y. Blackwell, T. Chun, J. Luster, Andrew TI The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak SO INFLAMMATION RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Scripps Res Inst, La Jolla, CA USA. EM aluster@partners.org NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD JUN PY 2007 VL 56 SU 3 BP S347 EP S347 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 182QA UT WOS:000247517900012 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Similar geographic variations in mortality from peptic ulcer and inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; death rates; duodenal ulcer; epidemiology; enteric infections; etiology of ulcerative colitis; gastric ulcer; mortality; time trends ID HELICOBACTER-PYLORI INFECTION; DUODENAL-ULCER; CROHNS-DISEASE; UNITED-STATES; RISK-FACTORS; TIME TRENDS; COLITIS; PREVALENCE; PERIOD AB Background: The epidemiology of peptic ulcer and inflammatory bowel disease shows many similar patterns. The aim of the present study was to compare the geographic distribution of mortality from peptic ulcer with that from inflammatory bowel disease. \ Methods: Mortality data from 27 countries between 1991 and 2004 were analyzed. The relationships between the geographic distributions of mortality from gastric ulcer, duodenal ulcer, Crohn's disease, and ulcerative colitis were compared using least-squares linear regression analyses. Results: The study revealed a 20- to 30-fold variation in mortality from peptic ulcer and a 60-fold variation in mortality from inflammatory bowel disease among different countries. Mortality from peptic ulcer and inflammatory bowel disease tended to be more common in northern European countries and rare in most countries in Asia and South America. The similar variations of all 4 diseases resulted in the correlations among their geographic distributions being statistically significant. Conclusions: The similarities in the geographic distributions of gastric ulcer, duodenal ulcer, Crohn's disease, and ulcerative colitis indicate that all 4 diseases may share a common set of risk factors. C1 Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM sonnenbe@ohsu.edu NR 33 TC 4 Z9 5 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 JUN PY 2007 VL 13 IS 6 BP 763 EP 768 DI 10.1002/ibd.20111 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 173SX UT WOS:000246893900013 PM 17260352 ER PT J AU Weylandt, KH Kang, JX Wiedenmann, B Baumgart, DC AF Weylandt, Karsten H. Kang, Jing X. Wiedenmann, Bertram Baumgart, Daniel C. TI Lipoxins and resolvins in inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Review DE inflammatory bowel disease; IBD; inflammation; immunology; dendritic cells; T cells; regulatory T cells; lipoxins; resolvins; omega-6; omega-3 ID INTESTINAL DENDRITIC CELLS; INDUCED COLITIS; IMMUNE-RESPONSES; PROSTAGLANDINS; BIOSYNTHESIS; TOLERANCE; MEDIATORS; RECEPTOR; ASPIRIN; BLOOD AB Lipid mediators are important messengers in many physiological processes. The pro-inflammatory effect of many prostaglandins. derived from the essential arachidonic acid, are well established. However, there are also anti-inflammatory lipid mediators: lipoxins and resolvins, derived from essential omega-6 and omega-3 polyunsaturated fatty acids (n-3 and n-6 PUFA), have been shown to control and resolve inflammation in a variety of experimental models of inflammatory disorders. Recent research implicates n-6 PUFA-derived lipoxins and their stable analogues as potent anti-inflammatory compounds in models of inflammatory bowel disease. Similarly, n-3 PUFA-derived lipid mediators such as resolvin E1 were shown to protect from experimental colitis in animal models. Some of their anti-inflammatory effects are mediated by dendritic cells. In this article we discuss the emerging knowledge on the effects of lipoxins and resolvins on various inflammatory pathways and why they are promising candidates for novel therapies of human inflammatory bowel disease. C1 Humboldt Univ, Virchow Hosp, Charite Med Sch, Dept Med,Div Hepatol & Gastroenterol, Berlin, Germany. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Baumgart, DC (reprint author), Humboldt Univ, Virchow Hosp Med Sch, Charite Med Ctr, Dept Med,Div Hepatol & Gastroenterol, D-13344 Berlin, Germany. EM daniel.baumgart@charite.de FU PHS HHS [R01 113605] NR 29 TC 27 Z9 27 U1 0 U2 4 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 JUN PY 2007 VL 13 IS 6 BP 797 EP 799 DI 10.1002/ibd.20109 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 173SX UT WOS:000246893900015 PM 17262807 ER PT J AU Franklin, J Malchau, H AF Franklin, John Malchau, Henrik TI Risk factors for periprosthetic femoral fracture SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE total hip arthroplasty; periprosthetic fracture; risk factors; prevention ID TOTAL HIP-REPLACEMENT; IPSILATERAL FEMUR; ARTHROPLASTY; PROSTHESIS; SHAFT; CHARNLEY; IMPLANTS AB Periprosthetic femur fractures are associated with high patient morbidity and are difficult reconstructive challenges. Early identification and appropriate intervention are critical to prevent this complication. Studies varying from case reports to national arthroplasty registry databases have demonstrated that certain factors are associated with an increased risk of fracture. These include trauma, patient-specific problems, and technical issues related to the hip replacement itself. Recent evidence from large registries has shown that the key to prevention of periprosthetic femur fractures is routine follow-up with radiographic studies. (C) 2007 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Adult Reconstruct Serv, Dept Orthopaed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA 02114 USA. RP Franklin, J (reprint author), Massachusetts Gen Hosp, Adult Reconstruct Serv, Dept Orthopaed, Yawkey Bldg Suite 3700-3B,55 Fruit St, Boston, MA 02114 USA. EM Jfranklin3@partners.org NR 36 TC 63 Z9 72 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD JUN PY 2007 VL 38 IS 6 BP 655 EP 660 DI 10.1016/j.injury.2007.02.049 PG 6 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 185YY UT WOS:000247747500003 PM 17467710 ER PT J AU Furniss, CS McClean, MD Smith, JF Bryan, J Nelson, HH Peters, ES Posner, MR Clark, JR Eisen, EA Kelsey, KT AF Furniss, C. Sloane McClean, Michael D. Smith, Judith F. Bryan, Janine Nelson, Heather H. Peters, Edwards S. Posner, Marshall R. Clark, John R. Eisen, Ellen A. Kelsey, Karl T. TI Human papillomavirus 16 and head and neck squamous cell carcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE human papillomavirus (HPV); head and neck squamous cell carcinoma (HNSCC); serology ID HUMAN-PAPILLOMAVIRUS INFECTION; CERVICAL-CANCER; ORAL-CANCER; TYPE-16; RISK; ANTIBODIES; VACCINE; HPV16; ASSAY; SUBSET AB Evidence suggests that human papillomavirus (HPV)16 seropositivity reflects past HPV16 exposure and is associated with risk for head and neck squamous cell carcinoma (HNSCC). Our objectives were to test the hypothesis that HPV16 seropositivity is associated with risk for HNSCC, to correlate HPV16 seropositivity with HPV16 tumor DNA, and to correlate HPV16 seropositivity and HPV16 DNA with sexual history and patient survival. In a case-control study of approximately 1,000 individuals, we assessed serology to the HPV16 L1 protein and in cases only, assayed tumors for HPV16 DNA. HPV16 seropositivity was associated with 1.5- and 6-fold risks for tumors of the oral cavity and pharynx, respectively. There was a dose response trend for HPV16 titer and increasing risk of HNSCC (p < 0.0001) and HPV16 tumor DNA (p < 0.0001). In cases, HPV16 DNA and seropositivity were significantly associated with sexual activity; odds ratios (ORs) of 12.8 and 3.7 were observed for more than 10 oral sexual partners and ORs of 4.5 and 3.2 were associated with a high number of lifetime sexual partners, respectively. Finally, HPV16 seropositivity and HPV16 tumor DNA were associated with hazard ratios of 0.4 and 0.5, respectively, indicating better survival for HPV positive individuals. HPV16 seropositivity was associated with risk for HNSCC, with greatest risk for pharyngeal cancer. We observed dose response relationships between serology titer and both risk for HNSCC and HPV16 tumor DNA. In cases, HPV16 tumor DNA and positive serology were associated with sexual history and improved disease free survival. (c) 2007 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Louisiana State Univ, Sch Publ Hlth, Dept Epidemiol, Baton Rouge, LA 70803 USA. Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Head & Neck Canc, Boston, MA 02114 USA. RP Kelsey, KT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. EM Kelsey@hsph.harvard.edu RI Kelsey, Karl/I-1252-2014; McClean, Michael/J-2934-2015; OI McClean, Michael/0000-0002-3902-8823; /0000-0003-4928-6532 FU NCI NIH HHS [CA100679, CA78609]; NIEHS NIH HHS [T32 ES07155] NR 34 TC 75 Z9 78 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 1 PY 2007 VL 120 IS 11 BP 2386 EP 2392 DI 10.1002/ijc.22633 PG 7 WC Oncology SC Oncology GA 156XV UT WOS:000245684100014 PM 17315185 ER PT J AU Phan, BAP Chu, BC Polissar, N Hatsukami, TS Yuan, C Zhao, XQ AF Phan, Binh An P. Chu, Baocheng Polissar, Nayak Hatsukami, Thomas S. Yuan, Chun Zhao, Xue-Qiao TI Association of high-density lipoprotein levels and carotid atherosclerotic plaque characteristics by magnetic resonance imaging SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; high-density lipoprotein; magnetic resonance imaging; carotid arteries ID IN-VIVO; HIGH-RESOLUTION; CHOLESTEROL; DISEASE; SIMVASTATIN; PREVENTION; REGRESSION; LESIONS; MILANO; MRI AB A low level of high-density lipoprotein cholesterol (HDL-C) is a risk factor for atherosclerotic disease. Magnetic resonance imaging (MRI) can provide detailed information on carotid atherosclerotic plaque size and composition. The purpose of this study was to correlate HDL levels with carotid plaque burden and composition by MRI. Thirty-four patients with coronary artery disease (CAD) receiving simvastatin plus niacin or placebo for both drugs for three years were randomly selected to undergo MRI of carotid arteries. Atherosclerotic plaque wall volumes (WVs) and plaque components including lipid rich/necrotic core (LR/NC), calcium, fibrous tissue, and loose matrix were measured. Mean WV or atherosclerotic burden was significantly associated with total HDL-C levels (r = -0.39, P = 0.02), HDL2 (r = -0.36, P = 0.03), HDL3 (r = -0.34, P = 0.04), and LDL/HDL ratio (r = 0.42, P = 0.02). Plaque lipid composition or LR/NC was significantly associated with HDL3 (r = -0.68, P = 0.02). Patients with low HDL levels (<= 35 mg/dL) had increased WV (97 +/- 23 vs. 81 +/- 19 mm(3), P = 0.05) compared with patients with HDL levels > 35 mg/dL. Among CAD patients, low HDL-C levels were significantly associated with increased carotid atherosclerotic plaque burden and lipid content by MRI. C1 Univ Washington, Div Cardiol, Dept Med, Seattle, WA 98103 USA. Washington Univ, Dept Radiol, Seattle, WA USA. Mt Whisper Light Stat Consulting, Seattle, WA USA. Washington Univ, Dept Surg, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Phan, BAP (reprint author), Univ Washington, Div Cardiol, Dept Med, 1914 N 34th St,Suite 105, Seattle, WA 98103 USA. EM bapp@u.washington.edu NR 23 TC 20 Z9 24 U1 2 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JUN PY 2007 VL 23 IS 3 BP 337 EP 342 DI 10.1007/s10554-006-9175-7 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 166PZ UT WOS:000246392600006 PM 17086362 ER PT J AU Cai, WL Harris, G Holalkere, N Sahani, D Yoshida, H AF Cai, Wenli Harris, Gordon Holalkere, Nagaraj Sahani, Dushyant Yoshida, Hiroyuki TI In-vivo and ex-vivo assessment of the accuracy of the computer-aided volumetry of porcine kidney in CT images SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Computer-aided detection; Kidney segmentation; Organ volumetry AB Measurement of kidney volume by computed tomography (CT), called renal volumetry, is indispensable for diagnosis and treatment of kidney-related diseases. Computer-aided volumetry (CAV) of kidney relies on an efficient and accurate segmentation method of the kidney. The purpose of this study is to assess the accuracy of our CAV of kidney scheme using dynamic-threshold (DT) level set method, based on in-vivo and ex-vivo reference standards. Eight Yorkshire breed anesthetized pigs were scanned on a 64-slice multi-detector CT scanner (Sensation 64, Siemens) after an injection of iodinated (300 mgI/ml) contrast agent through an IV cannula. The kidneys of the pigs were then surgically resected and scanned on CT in the same manner. Both in-vivo and ex-vivo CT images were subjected to our volumetry scheme. The resulting volumes of the kidneys were compared with the in-vivo and ex-vivo reference standards: the former was established by manual contouring of the kidneys on the CT images by an experienced radiologist, and the latter was established as the water displacement volume of the resected kidney. Our CAV of kidney scheme demonstrated accurate in-vivo and ex-vivo measurement of kidney volume, despite a large difference between the two reference standards. C1 [Cai, Wenli] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUN PY 2007 VL 2 SU 1 BP S384 EP S386 PG 3 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZD UT WOS:000208988200201 ER PT J AU Haupl, T de Kleine, R Lochmann, C Schultz, CP AF Haeupl, T. de Kleine, R. Lochmann, C. Schultz, C. P. TI Matched functional and morphological Imaging: new intra-operative NIR-fluorescence imaging device SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Multi-channel spectral imaging device; ICG fluorescence; Lymph nodes; Image matching AB An intra-operative imaging device for combined near infrared fluorescence and native imaging is presented. Two spectrally separated channels for different contrast agents (i.e. indocyanine green = ICG, AngioSense 750, Cy5.5, ProSense 680) are matched with the field of view of the native image. First examples of application are sentinel lymph node detection in the vicinity of a surgically resected tumor by means of ICG fluorescence and in vivo imaging of tumor tissue in mice. C1 [de Kleine, R.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Lochmann, C.] Charite, Inst Med Phys & Laser Med, Berlin, Germany. [Schultz, C. P.] Siemens AG, Med Solut, Boston, MA USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUN PY 2007 VL 2 SU 1 BP S186 EP S188 PG 3 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZD UT WOS:000208988200098 ER PT J AU Lefere, P Gryspeerdt, S Yoshida, H AF Lefere, P. Gryspeerdt, S. Yoshida, H. TI CT colonography: current status in Europe and future perspectives SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Virtual colonoscopy; Fecal tagging; Oral contrast agents; Barium; Computer-aided diagnosis AB In this article, we review the current status of CT colonography (CTC) in Europe and future perspectives of CTC including fecal tagging and CAD. There are several large multi-centre studies that have been initiated. Fecal tagging has gradually become a prerequisite to perform state-of-the-art CTC. However, CAD for fecal-tagging CTC remains a subject for future research. C1 [Lefere, P.] Stedelijk Ziekenhuis, Roeselare, Belgium. [Yoshida, H.] Massachussets Gen Hosp, Boston, MA USA. RP Lefere, P (reprint author), Stedelijk Ziekenhuis, Roeselare, Belgium. NR 25 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUN PY 2007 VL 2 SU 1 BP S373 EP S374 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZD UT WOS:000208988200195 ER PT J AU Manzke, R Tournoux, F van der Brink, BD Gerard, O van der Boomen, RD Shechter, G Gutierrez, L Singh, J Picard, M Chan, RC AF Manzke, R. Tournoux, F. v d Brink, B. Gerard, O. v d Boomen, R. Shechter, G. Gutierrez, L. Singh, J. Picard, M. Chan, R. C. TI Interventional guidance for cardiac resynchronization therapies: merging anatomic X-ray imaging with functional ultrasound imaging based on mutually-shared landmarks SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Cardiac electrophysiology; Interventional guidance; Image guided therapies; Cardiac resynchronization therapies; Multi-modality imaging AB Detailed knowledge of cardiac anatomy and function is required for complex cardiac electrophysiology interventions. Cardiac resynchronization therapies (CRT), for example, requires information about coronary venous anatomy for left ventricular lead placement. In CRT, heart failure patients are equipped with dual-chamber pacemakers in order to improve cardiac output and heart failure symptoms. Cardiac function is mainly assessed with Ultrasound imaging. Fusion of complementary information from X-ray and Ultrasound is an essential step towards fully utilizing all available information for CRT guidance. We present an approach for fusion of anatomical information (coronary vein structure) from X-ray with functional information (left ventricular deformation and dynamics) from Ultrasound. We propose an image-based fusion approach based on mutually-shared landmarks which enable registration of both imaging spaces without the need for external tracking. C1 [Manzke, R.; Shechter, G.; Gutierrez, L.; Chan, R. C.] Philips Res North Amer, Briarcliff Manor, NY 10510 USA. [Tournoux, F.; Singh, J.; Picard, M.] Harvard Univ, Sch Med, Dept Cardiol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [v d Brink, B.; v d Boomen, R.] Philips Med Syst, Best, Netherlands. [Gerard, O.] Philips Med Syst, Paris, France. RP Manzke, R (reprint author), Philips Res North Amer, Briarcliff Manor, NY 10510 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUN PY 2007 VL 2 SU 1 BP S236 EP S237 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZD UT WOS:000208988200123 ER PT J AU Nappi, J Yoshida, H Cai, W Lefere, P AF Naeppi, J. Yoshida, H. Cai, W. Lefere, P. TI Optimized target ranking for high-performance CAD in CT colonography SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Ranking; Polyp detection; Computer-aided detection; CT colonography; Virtual colonoscopy AB Most CAD systems that detect target lesions at a high sensitivity yield a large amount of initial detections that need to be analyzed by time-consuming FP reduction steps. We developed an optimized target ranking (OTR) method that minimizes the set of initial detections in a CAD system for CT colonography (CTC): the initial CAD detections from patient's volumetric CT scans are collected into a single by-patient detection pool, and an optimal classifier is used to select detections that are most likely to represent polyps based on training data. We optimized the OTR method by use of a training database including 71 CTC polyp cases, and integrated the method into a previously developed fully automated CAD system that was trained with 146 CTC cases from three institutions. We then compared the effect of the OTR method on the CAD system with that of a conventional by-feature candidate selection method by use of an independent testing database including 450 prospective asymptomatic CTC screening [GRAPHICS] cases at a clinically acceptable range of an average of 0-3 false-positive detections per CT scan. The OTR method reduced the number of initial CAD detections by 89% without degrading the final 92% detection sensitivity for adenomas >= 8 mm, thereby exceeding the 85% sensitivity of prospective human CTC reading. In summary, the OTR method is an effective approach for reducing initial FP CAD detections without degrading the performance of automated polyp detection in CTC. C1 [Naeppi, J.; Yoshida, H.; Cai, W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Naeppi, J.; Yoshida, H.; Cai, W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Lefere, P.] Stedelijk Ziekenhuis, Roeselare, Belgium. RP Nappi, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUN PY 2007 VL 2 SU 1 BP S380 EP S381 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZD UT WOS:000208988200199 ER PT J AU Nappi, J AF Naeppi, J. TI CAD for CT colonography: toward a preparation-independent scheme SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Computer-aided detection; CAD; CT colonography; Colon preparation; Virtual colonoscopy AB Computer-aided detection (CAD) systems can be used to automatically detect and display the locations of polyps and masses in computed tomographic colonography (CTC) data for assisting radiologists' image interpretation. Rapid technical advancements over the last few years have established a fundamental CAD scheme for CTC that includes the steps of colon extraction, polyp detection, and false-positive (FP) reduction. Several CAD prototype systems have demonstrated clinically acceptable high polyp detection sensitivity with relatively few FP detections in cathartic CTC, and observer studies have demonstrated the potential benefit of such systems in improving the accuracy and consistency of radiologists' detection performance. Some CAD prototype systems have also demonstrated promising performance in reduced cathartic and non-cathartic CTC. Recent advancements suggest that CAD systems can soon be expected to provide a preparation-independent scheme that can yield consistently high detection sensitivity with moderately low FP rate not only with cathartic CTC protocols but over a wide range of cathartic, reduced cathartic, and non-cathartic CTC protocols. C1 [Naeppi, J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Naeppi, J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Nappi, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUN PY 2007 VL 2 SU 1 BP S375 EP S376 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZD UT WOS:000208988200196 ER PT J AU Chen, PJ Kales, HC Weintraub, D Blow, FC Jiang, L Ignacio, RV Mellow, AM AF Chen, Peijun Kales, Helen C. Weintraub, Daniel Blow, Frederic C. Jiang, Lan Ignacio, Rosalinda V. Mellow, Alan M. TI Depression in veterans with Parkinson's disease: frequency, co-morbidity, and healthcare utilization SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY MAR 03-06, 2005 CL San Diego, CA SP Amer Assoc Geriatr Psychiat DE depression; Parkinson's disease; frequency; co-morbidity; healthcare utilization ID NONMOTOR SYMPTOMS; DEMENTIA; PREVALENCE; PSYCHOSIS; LIFE AB Objective To determine the frequency of depression in Parkinson's disease (PD) in routine clinical care, and to examine its association with co-morbid psychiatric and medical conditions and healthcare utilization. Methods Depression diagnoses and healthcare utilization data for all male veterans with PD age 55 or older seen in fiscal year 2002 (n = 41,162) were analyzed using Department of Veterans Affairs (VA) national databases. Frequencies of co-morbid disorders and healthcare utilization were determined for depressed and non-depressed patients; associations with depression were examined using multivariate logistic regression models. Results A depression diagnosis was recorded for 18.5% of PD, patients, including major depression in 3.9%. Depression decreased in frequency and severity with increasing age. In multivariate logistic regression models, depressed patients had significantly greater psychiatric and medical co-morbidity, including dementia, psychosis, stroke, congestive heart failure, diabetes, and chronic obstructive pulmonary disease than non-depressed patients (all p < 0.01). Depressed PD patients were also significantly more likely to have medical (OR = 1.34, 95% CI = 1.25-1.44) and psychiatric hospitalizations (OR = 2.14, 95% CI = 1.83-2.51), and had more outpatient visits (p < 0.01), than non-depressed PD) patients in adjusted models. Conclusion Depression in PD in non-tertiary care settings may not be as common or as severe as that seen in specialty care, though these findings also may reflect under-recognition or diagnostic imprecision. The occurrence of depression in PD is associated with greater psychiatric and medical co-morbidity, and greater healthcare utilization. These findings suggest that screening for depression in PD is important and should be embedded in a comprehensive psychiatric, neuropsychological, and medical evaluation. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Univ Michigan, Dept Psychiat, Div Geriatr Psychiat, Ann Arbor, MI 48109 USA. VA Natl Serious Mental Illness Treatment Res & Ev, Ann Arbor, MI USA. VA Ann Arbor Healthcare Syst, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Parkinsons Dis & Mental Illness Res Educ & Clin C, PADRECC, Philadelphia, PA USA. Philadelphia VA Med Ctr, MIRECC, Philadelphia, PA USA. VISN 11 Mental Hlth Serv Line, Dept Vet Affairs, Ann Arbor, MI USA. RP Chen, PJ (reprint author), Cleveland VA Med Ctr, Psychiat Serv 116A B, 10000 Brecksville Rd, Brecksville, OH 44141 USA. EM Peijun.chen@med.va.gov FU NIMH NIH HHS [K23 MH067894, K23 MH067894-04] NR 33 TC 18 Z9 20 U1 3 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JUN PY 2007 VL 22 IS 6 BP 543 EP 548 DI 10.1002/gps.1712 PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 181OO UT WOS:000247446200005 PM 17133656 ER PT J AU Nokihara, K Yasuhara, T Nakata, Y Lerner, EA Wray, V AF Nokihara, Kiyoshi Yasuhara, Tadashi Nakata, Yoshihiro Lerner, Ethan A. Wray, Victor TI Chemical synthesis of maxadilan, a non-mammalian potent vasodilatory peptide consisting of 61 amino acids with two disulfide bridges, and its related peptides SO INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS LA English DT Article DE vasodilator; maxadilan; PAC1 receptor; disulfide isomer; highly efficient solid-phase synthesis; difficult sequence; melanophore assay ID CYCLASE-ACTIVATING POLYPEPTIDE; SOLID-PHASE SYNTHESIS; ADENYLATE-CYCLASE; RECEPTORS; GLAND AB A potent and persistent non-mammalian derived vasodilator, maxadilan (Maxa) consists of 61 amino acids with two disulfide linkages and acts as an agonist of the type I receptor of pituitary adenylate cyclase activating polypeptide (PACAP), although there is very little sequence similarity. The total chemical syntheses of Maxa, its disulfide isomers and various fragments have been performed successfully by highly efficient solid-phase peptide synthesis (SPPS). A "difficult sequence", envisaged in the middle region of Maxa, could be overcome by improved synthesis protocols. After assembly peptides were liberated from the resin by cleavage. Peptides having disulfide(s) were purified by two steps of preparative HPLC using cation exchange followed by reverse phase columns. Purified peptides were characterized by HPLC, Edman-sequencing, amino acid analysis and mass spectrometry in addition to disulfide form determination. The peptides obtained were used for recognition studies by the melanophore assay to confirm the native disulfide form. Peptide libraries related to Maxa, produced in the present study, will be useful for the elucidation of the structural requirements of Maxa for interaction with the PACAP type 1 receptor (PAC1). C1 HiPep Labs, Kamigyo Ku, Kyoto 6028158, Japan. Tokyo Univ Agr, Setagaya Ku, Tokyo 1560054, Japan. Hiroshima Univ, Hiroshima 7348551, Japan. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Helmholtz Ctr Infect Res, Dept Biol Struct, D-38124 Braunschweig, Germany. RP Nokihara, K (reprint author), HiPep Labs, Kamigyo Ku, Nakatsukasa Cho 486-46, Kyoto 6028158, Japan. EM noki@hipep.jp NR 25 TC 8 Z9 8 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1573-3149 EI 1573-3904 J9 INT J PEPT RES THER JI Int. J. Pept. Res. Ther. PD JUN PY 2007 VL 13 IS 1-2 BP 377 EP 386 DI 10.1007/s10989-007-9097-9 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 178QZ UT WOS:000247236500041 ER PT J AU Viswanathan, AN Dimopoulos, J Kirisits, C Berger, D Potter, R AF Viswanathan, Akila N. Dimopoulos, Johannes Kirisits, Christian Berger, Daniel Potter, Richard TI Computed tomography versus magnetic resonance imaging-based contouring in cervical cancer brachytherapy: Results of a prospective trial and preliminary guidelines for standardized contours SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 25th Congress of the European-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 08-12, 2006 CL Leipzig, GERMANY SP European Soc Therapeut Radiol & Oncol DE cervical cancer; brachytherapy; computed tomography; magnetic resonance imaging ID INTRACAVITARY GYNECOLOGIC IMPLANTS; DOSE-RATE BRACHYTHERAPY; HDR-BRACHYTHERAPY; CT; CARCINOMA; MRI; RECOMMENDATIONS; RADIATION; BLADDER; RECTUM AB Purpose: To compare the contours and dose-volume histograms (DVH) of the tumor and organs at risk (OAR) with computed tomography (CT) vs. magnetic resonance imaging (MRI) in cervical cancer brachytherapy. Methods and Materials: Ten patients underwent both MRI and CT after applicator insertion. The dose received by at least 90% of the volume (D-90), the minimal target dose (D-100), the volume treated to the prescription dose or greater for tumor for the high-risk (HR) and intermediate-risk (IR) clinical target volume (CTV) and the dose to 0.1 cm(3), 1 cm(3), and 2 cm(3) for the OARs were evaluated. A standardized approach to contouring on CT (CTStd) was developed, implemented (HR- and IR-CTVCTStd), and compared with the MRI contours. Results: Tumor height, thickness, and total volume measurements, as determined by either CT or CTStd were not significantly different compared with the MRI volumes. In contrast, the width measurements differed in HR-CTVCTStd (p = 0.05) and IR-CTVCTStd(p = 0.01). For the HR-CTVCTStd, this resulted in statistically significant differences in the volume treated to the prescription dose or greater (MRI, 96% vs. CTStd, 86 %, p = 0.01), D-100 (MRI, 5.4 vs. CTStd, 3.4, p < 0.01), and D-90 (MRI, 8.7 vs. CTStd, 6.7, p < 0.01). Correspondingly, the IR-CTV DVH values on MRI vs. CTStd, differed in the D-100 (MRI, 3.0 vs. CTStd, 2.2, p = 0.01) and D-90 (MRI, 5.6 vs. CTStd, 4.6, p = 0.02). The MRI and CT DVH values of the dose to 0.1 cm(3), 1 cm(3), and 2 cm(3) for the OARs were similar. Conclusion: Computed tomography-based or MRI-based scans at brachytherapy are adequate for OAR DVH analysis. However, CT tumor contours can significantly overestimate the tumor width, resulting in significant differences in the D90, D100, and volume treated to the prescription dose or greater for the HR-CTV compared with that using MRI. MRI remains the standard for CTV definition. (C) 2007 Elsevier Inc. C1 Med Univ Vienna, Dept Radiotherapy & Radiobiol, A-1090 Vienna, Austria. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Dimopoulos, J (reprint author), Med Univ Vienna, Gen Hosp Vienna, Dept Radiotherapy & Radiobiol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM Johannes.dimopoulos@akhwien.at OI Viswanathan, Akila/0000-0002-2003-0392; Kirisits, Christian/0000-0002-2815-8083 FU NCI NIH HHS [1K07 CA117979-01] NR 33 TC 210 Z9 220 U1 2 U2 10 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 JUN 1 PY 2007 VL 68 IS 2 BP 491 EP 498 DI 10.1016/j.ijrobp.2006.12.021 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 171IS UT WOS:000246730000025 PM 17331668 ER PT J AU Stahl, JE Vacanti, JP Gazelle, S AF Stahl, James E. Vacanti, Joseph P. Gazelle, Scott TI Assessing emerging technologies - The case of organ replacement technologies: Volume, durability, cost SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article DE organ replacement technology; transplant; cost-effectiveness; discrete-event simulation ID XENOTRANSPLANTATION; TRANSPLANTATION AB Objectives: The aim of this study was to estimate thresholds for production volume, durability, and cost of care for the cost-effective adoption of liver organ replacement technologies (ORTs). Methods: We constructed a discrete-event simulation model of the liver allocation system in the United States. The model was calibrated against UNOS data (1994-2000). Into this model, we introduced ORTs with varying durability (time to failure), cost of care, and production volume. Primary outputs of interest were time to 5 percent reduction in the waiting list and time to 5 percent increase in expected transplant volume. Results: Model output for both calibration and validation phases closely matched published data: waiting list length (+/- 2 percent), number of transplants (+/- 2 percent), deaths while waiting (+/- 5 percent), and time to transplant (+/- 1 1 percent). Reducing the waiting list was dependent on both ORT durability and production volume. The longer the durability, the less production volume needed to reduce the waiting list and vice versa. However, below 250 ORT/year, durability needed to be > 2 years for any significant change to be seen in the waiting list. For base-case costs, all ORT production volume and durability scenarios result in more transplants per year at less total cost of care/patient than the current system. ORTs remain cost saving until manufacturing costs are > 5 times base-case costs, production is less 500 ORT/year, and durability < 6 months. Conclusions: Although there remain many technical challenges to overcome, as long as ORTs can meet these threshold criteria, they have the potential of transforming the world of end-stage liver disease. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02114 USA. RP Stahl, JE (reprint author), Harvard Univ, Sch Med, Dept Med, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM James@mgh-ita.org; jvacanti@partners.org NR 22 TC 5 Z9 5 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0266-4623 EI 1471-6348 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD SUM PY 2007 VL 23 IS 3 BP 331 EP 336 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA 187KF UT WOS:000247845800005 PM 17579935 ER PT J AU Berlanga, M Paster, BJ Guerrero, R AF Berlanga, Mercedes Paster, Bruce J. Guerrero, Ricardo TI Coevolution of symbiotic spirochete diversity in lower termites SO INTERNATIONAL MICROBIOLOGY LA English DT Article DE symbiotic spirochetes; termite gut spirochetes; ectosymbionts; symbiotic protists; lower termites; coevolution ID IN-SITU IDENTIFICATION; PHYLOGENETIC DIVERSITY; MASTOTERMES-DARWINIENSIS; BACTERIAL COMMUNITY; SP-NOV.; GUT; HINDGUT; LOCALIZATION; MICROBIOTA; PROTISTS AB The phylogenetic relationships of symbiotic spirochetes from five dry-wood feeding lower termites (Cryptotermes cavifrons, Heterotermes tenuis, Kalotermes flavicollis, Neotermes mona, and Reticulitermes grassei) was compared to those described in previous reports. The 16S rDNA bacterial genes were PCR-amplified from DNA isolated from intestinal samples using a spirochete-selective primer, and the 16S amplicons were cloned into Escherichia coli. Sequences of the cloned inserts were then used to determine closest relatives by comparison with published sequences. Clones sharing more than 97% sequence identity were grouped into the same phylotype. Forty-three new phylotypes were identified. These termite whole-gut-spirochetes fell into two previous defined clusters, designated as Treponema Clusters I and II, and one new Cluster Ill. Thirty-seven phylotypes were grouped in Cluster 1. Cluster 11 comprised three phylotypes, two from Reticulitermes grassei (LJ029 and LJ012) and one from Heterotermes tenuis (LQ016). Three phylotypes, LK057, LK050 and LK028, were affiliated to Cluster III. Members of Cluster I showed the following characteristics: (i) spirochete phylotypes from a particular species of termite were more closely related to each other than to phylotypes of other termite species; (ii) spirochetes obtained from different genera of the same family, such as Cryptotermes sp., Kalotermes sp., and Neotermes sp., all from the family Kalotermitidae, were also related to each other. It was therefore concluded that spirochetes are specific symbionts that have coevolved with their respective species of termites, are stably harbored, and are closely related to members of the same termite family. C1 Univ Barcelona, Fac Pharm, Dept Microbiol & Parasitol, E-08028 Barcelona, Spain. Forsyth Inst, Dept Mol Genet, Boston, MA USA. Univ Barcelona, Fac Biol, Dept Microbiol, E-08028 Barcelona, Spain. RP Berlanga, M (reprint author), Univ Barcelona, Fac Pharm, Dept Microbiol & Parasitol, Av Joan XXIII,S-N, E-08028 Barcelona, Spain. EM mberlanga@ub.edu OI Berlanga, Mercedes/0000-0002-7305-7046 FU NIDCR NIH HHS [DE-10374, DE-11443] NR 33 TC 17 Z9 17 U1 1 U2 10 PU VIGUERA EDITORES, S L PI BARCELONA PA PLAZA TETUAN, 7, BARCELONA, E-08010, SPAIN SN 1139-6709 J9 INT MICROBIOL JI Int. Microbiol. PD JUN PY 2007 VL 10 IS 2 BP 133 EP 139 DI 10.2436/20.1501.01.19 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 195WZ UT WOS:000248444400009 PM 17661292 ER PT J AU Faison, WE Schultz, SK Aerssens, J Alvidrez, J Anand, R Farrer, LA Jarvik, L Manly, J Mcrae, T Murphy, GM Olin, JT Regier, D Son, M Mintzer, JE AF Faison, Warachal E. Schultz, Susan K. Aerssens, Jeroen Alvidrez, Jennifer Anand, Ravi Farrer, Lindsay A. Jarvik, Lissy Manly, Jennifer McRae, Thomas Murphy, Greer M., Jr. Olin, Jason T. Regier, Darrel Son, Mary Mintzer, Jacobo E. TI Potential ethnic modifiers in the assessment and treatment of Alzheimer's disease: challenges for the future SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE dementia; Alzheimer's disease; genetics; minority issues and cross-cultural psychiatry; social and political issues ID CANCER SCREENING TRIAL; NEUROPSYCHOLOGICAL TEST-PERFORMANCE; PROSTATE-SPECIFIC ANTIGEN; AFRICAN-AMERICAN ELDERS; CLINICAL-TRIALS; RECRUITMENT EXPERIENCE; RACIAL-DIFFERENCES; COGNITIVE DECLINE; DIVERSE ELDERS; READING LEVEL AB Objective: Despite numerous clinical trials, it is unknown whether ethnicity affects treatment response to cognitive enhancers in Alzheimer's disease (AD). There is convincing evidence of ethnic and genetic variability in drug metabolism. This article reviews the available data on ethnicity in clinical trials for AD to answer two questions: (1) what are the challenges to diagnose and treat AD across different ethnic groups, and (2) are there differences in response to pharmacologic interventions for AD across these different ethnic groups? Method: Available data from Alzheimer's Disease Cooperative Study (ADCS) randomized controlled clinical trials and from randomized controlled industry-sponsored trials for four cognitive enhancers (donepezil, galantamine, rivastigmine and sabeluzole) were pooled to assess the numbers of non-Caucasian participants. Results: The participation of ethnic minority subjects in clinical trials for AD was dependent on the funding source, although Caucasian participants were over-represented and non-Caucasian participants were under-represented in the clinical trials. Because of the low participation rate of ethnic minorities, there were insufficient data to assess any differences in treatment outcome among different ethnic groups. Strategies to improve diversity in clinical trials are discussed. Conclusion: Greater participation of ethnically diverse participants in clinical trials for AD would generate additional information on possible differences in metabolism, treatment response, adverse events to therapeutic agents, and could foster the investigation of genetic variability among ethnic groups. C1 Med Univ S Carolina, Alzheimers Res & Clin Programs, Dept Neurosci, N Charleston, SC 29406 USA. Univ Iowa, Coll Med, Iowa City, IA USA. Janssen Pharmaceut NV, Johnson & Johnson Pharmaceut Res & Dev, Dept Internal Med, Beerse, Belgium. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Anand Pharma Consulting, Oberwil, Switzerland. Boston Univ, Sch Med, Genet Program, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Dept Vet Affairs, Los Angeles, CA USA. Columbia Univ, Med Ctr, New York, NY USA. Pfizer Inc, Alzheimers Dis Management Team, New York, NY USA. NYU, Sch Med, New York, NY USA. Stanford Univ, Sch Med, Neurosci Res Labs, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Forest Res Inst, Jersey, NJ USA. Amer Psychiat Assoc, Div Res, Arlington, VA USA. APIRE, Arlington, VA USA. Mt Sinai Sch Med, Alzheimer Dis Res Ctr, Bronx, NY USA. James J Peters VA Med Ctr, Bronx, NY USA. Med Univ S Carolina, Dept Neurosci, Div Translat Res, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Faison, WE (reprint author), Med Univ S Carolina, Alzheimers Res & Clin Programs, Dept Neurosci, 5900 Core Rd,Suite 203, N Charleston, SC 29406 USA. EM faison@musc.edu OI Farrer, Lindsay/0000-0001-5533-4225 NR 95 TC 25 Z9 25 U1 2 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD JUN PY 2007 VL 19 IS 3 BP 539 EP 558 DI 10.1017/S104161020700511X PG 20 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA 175AQ UT WOS:000246984800016 PM 17451614 ER PT J AU Rosenblatt, PL Ferzandi, T Sasson, S Pulliam, SJ AF Rosenblatt, P. L. Ferzandi, T. Sasson, S. Pulliam, S. J. TI Transobturator postanal sling (TOPAS) for the treatment of anal incontinence SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Meeting Abstract C1 Mt Auburn Hosp, Cambridge, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD JUN PY 2007 VL 18 SU 1 MA 406 BP S217 EP S217 PG 1 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 192FD UT WOS:000248185300378 ER PT J AU Nakazawa, T Takeda, M Lewis, GP Cho, KS Jiao, JW Wilhelmsson, U Fisher, SK Pekny, M Chen, DF Miller, JW AF Nakazawa, Toru Takeda, Masumi Lewis, Geoffrey P. Cho, Kin-Sang Jiao, Jianwei Wilhelmsson, Ulrika Fisher, Steven K. Pekny, Milos Chen, Dong F. Miller, Joan W. TI Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INTERMEDIATE-FILAMENTS; MACULAR DEGENERATION; CELL CHANGES; MULLER CELL; EXPRESSION; ASTROCYTES; APOPTOSIS; REGENERATION; INJURY; CONSEQUENCES AB PURPOSE. To characterize the reactions of retinal glial cells (astrocytes and Muller cells) to retinal injury in mice that lack glial fibrillary acidic protein (GFAP) and vimentin (GFAP(-/-)Vim(-/-)) and to determine the role of glial cells in retinal detachment (RD)-induced photoreceptor degeneration. METHODS. RD was induced by subretinal injection of sodium hyaluronate in adult wild-type (WT) and 6FAP(-/-)Vim(-/-) mice. Astroglial reaction and subsequent monocyte recruitment were quantified by measuring extracellular signal-regulated kinase (Erk) and c-fos activation and the level of expression of chemokine monocyte chemoattractant protein (MCP)-1 and by counting monocytes/microglia in the detached retinas. Immunohistochemistry, immunoblotting, real-time quantitative polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used. RD-induced photoreceptor degeneration was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and measurement of outer nuclear layer (ONL) thickness. RESULTS. RD-induced reactive gliosis, characterized by GFAP and vimentin upregulation, Erk and c-fos activation, MCP-1 induction, and increased monocyte recruitment in WT mice. Absence of GFAP and vimentin effectively attenuated reactive responses of retinal glial cells and monocyte infiltration. As a result, detached retinas of GFAP(-/-)Vim(-/-) mice exhibited significantly reduced numbers of TUNEL-positive photoreceptor cells and increased ONL thickness compared with those of WT mice. CONCLUSIONS. The absence of GFAP and vimentin attenuates RD-induced reactive gliosis and, subsequently, limits photoreceptor degeneration. Results of this study indicate that reactive retinal glial cells contribute critically to retinal damage induced by RD and provide a new avenue for limiting photoreceptor degeneration associated with RD and other retinal diseases or damage. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Eye & Ear Infirm,Angiogenesis Lab, Boston, MA 02115 USA. Asahikawa Med Coll, Dept Ophthalmol, Asahikawa, Hokkaido 078, Japan. Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA. Gothenburg Univ, Sahlgrenska Acad, Ctr Brain Repair & Rehabil, Dept Clin Neurosci & Rehabil, S-41124 Gothenburg, Sweden. RP Chen, DF (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM dongfeng.chen@schepens.harvard.edu; jwmiller@meei.harvard.edu RI Jiao, Jianwei/I-1452-2013 OI Jiao, Jianwei/0000-0002-7893-0721 FU NEI NIH HHS [EY012983, EY003790, EY00888, EY014104, P30 EY003790, P30 EY014104, R01 EY000888, R01 EY012983, R01 EY017641, R01 EY017641-01A2, R37 EY000888] NR 44 TC 85 Z9 89 U1 1 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2007 VL 48 IS 6 BP 2760 EP 2768 DI 10.1167/iovs.06-1398 PG 9 WC Ophthalmology SC Ophthalmology GA 174UA UT WOS:000246967100039 PM 17525210 ER PT J AU Dolan, SE Carpenter, S Grinspoon, S AF Dolan, Sara E. Carpenter, Sara Grinspoon, Steven TI Effects of weight, body composition, and testosterone on bone mineral density in HIV-infected women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE androgen deficiency; bone mineral density; HIV; women ID X-RAY ABSORPTIOMETRY; WASTING SYNDROME; DEFICIENCY; OSTEOPENIA; RISK; OSTEOPOROSIS; FRACTURE; MEN; FAT AB Recent studies suggest that bone loss occurs among HIV-infected women. This study examined the effects of reduced androgen levels, changes in weight, body composition, and menstrual dysfunction on bone mineral density (BMD) among 152 HIV-infected wornen characterized by normal weight (>90% ideal body weight [IBW], n = 124) and low weight (<= 90% IBW, n = 28) compared with 100 non-HIV-infected control subjects. BMD was assessed by dual x-ray absorptiometry, and free testosterone was assessed by equilibrium dialysis. Abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were determined by computed tomography scan. A significant difference was seen in BMD between groups at the lumbar spine (0.92 +/- 0.02 g/cm(2) vs. 1.01 +/- 0.01 g/cm(2) vs. 1.07 +/- 0.01 g/cm(2); P < 0.0001), total hip (0.84 +/- 0.03 g/cm(2) vs. 0.94 +/- 0.01 g/cm(2) vs. 0.98 +/- 0.01 g/cm(2); P < 0.000 1), and femoral neck (0.73 +/- 0.03 g/cm(2) vs. 0.83 +/- 0.01 g/cm(2) vs. 0.87 +/- 0.01 g/cm(2); P < 0.0001) (HIV-infected low-weight group, HIV-infected normal-weight group, and non-HIV-infected control subjects, respectively, for each comparison; mean - SEM). Among the HIV-infected subjects, lumbar BMD correlated with percent IBW (r = 0.37, P < 0.0001), total body lean mass (r = 0.43, P < 0.0001), total body fat mass (r = 0.35, P < 0.0001), and SAT (r = 0.41, P < 0.0001), but not VAT (r = 0.07, P = 0.417). Clinical risk factors for osteopenia and osteoporosis in the HIV population identified in univariate analysis included low free testosterone (<1.1 pg/mL [lower limit of the normal range of free testosterone for women] or 3.8 pmol/L; P = 0.0007), low weight (P = 0.014), and oligomenorrhea (P = 0.0006). In multivariate regression analysis, lean body mass was most significantly associated with BMD among those with HIV These data demonstrate that BMD is reduced among HIV-infected women in association with low weight, reduced lean mass, reduced androgen levels, and abnormal menstrual function. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutr Metab, Longfellow 207,55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [R01DK59535, P30 DK040561, R01DK54167, P30 DK040561-12] NR 23 TC 23 Z9 23 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 JUN 1 PY 2007 VL 45 IS 2 BP 161 EP 167 DI 10.1097/QAI.0b013e31804a7f4d PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 173SD UT WOS:000246891900006 PM 17527091 ER PT J AU Alford, DP Salsitz, EA Martin, J Renner, JA AF Alford, Daniel P. Salsitz, Edwin A. Martin, Judith Renner, John A. TI Clinical case discussion: Treating opioid dependence with buprenorphine SO JOURNAL OF ADDICTION MEDICINE LA English DT Editorial Material DE opioid; opioid dependence; buprenorphine ID METHADONE-MAINTENANCE C1 [Alford, Daniel P.] Boston Univ, Dept Med,Off Based Opioid Treatment Program, Gen Internal Med Sect,Sch Med, CARE Unit,Boston Med Ctr, Boston, MA 02118 USA. [Salsitz, Edwin A.] Beth Israel Deaconess Med Ctr, Dept Med, Off Based Opioid Therapy, New York, NY 10003 USA. [Martin, Judith] 14th St Clin, Oakland, CA USA. [Martin, Judith] E Bay Community Recovery Project, Oakland, CA USA. [Renner, John A.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Boston, MA 02118 USA. RP Alford, DP (reprint author), Boston Univ, Dept Med,Off Based Opioid Treatment Program, Gen Internal Med Sect,Sch Med, CARE Unit,Boston Med Ctr, 91 E Concord St,Suite 200, Boston, MA 02118 USA. EM dan.alford@bmc.org NR 10 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD JUN PY 2007 VL 1 IS 2 BP 73 EP 78 DI 10.1097/ADM.0b013e3180691158 PG 6 WC Substance Abuse SC Substance Abuse GA 305GK UT WOS:000256165700004 PM 21768938 ER PT J AU Angarita, GA Reif, S Pirard, S Sharon, E Gastfriend, DR AF Angarita, Gustavo A. Reif, Sharon Pirard, Sandrine Sharon, Estee Gastfriend, David R. TI No-show for treatment in substance abuse patients with comorbid symptomatology: Validity results from a controlled trial of the ASAM patient placement criteria SO JOURNAL OF ADDICTION MEDICINE LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the International-Society-of-Addiction-Medicine CY SEP 27-30, 2006 CL Oporto, PORTUGAL SP Int Soc Addict Med DE substance use disorder; no-shows; ASAM levels of care; treatment matching criteria; co-occurring disorders ID NATIONAL EPIDEMIOLOGIC SURVEY; ADDICTION SEVERITY INDEX; DUAL DIAGNOSIS; SOCIAL ANXIETY; USE DISORDERS; RATING-SCALE; ALCOHOL; DEPRESSION; PREVENTION; SERVICES AB Purpose: Mismatched placement, according to the American Society of Addiction Medicine's (ASAM) Patient Placement Criteria (PPC), promotes no-shows to treatment; however, little is known about the impact on patients with psychiatrically comorbid substance use disorder. Methods: In a multisite trial, public-sector treatment-seeking adults (N = 700), following a computer-assisted ASAM PPC-1 structured interview, were blindly scored and randomly assigned to Level-of-Care (LOC)-II (intensive outpatient) or LOC-III (residential) settings. Patients scored as needing LOC-II but assigned to LOC-III were, by definition, "oven-natched." Results: Among 143 overmatched patients, no-shows were significantly higher in comorbids versus noncomorbids (54% versus 28%; P < 0.01). Among overmatched comorbids, patients who no-showed compared with patients who showed were more likely to be females (70.4% versus 34.8%; P < 0.05), to have anxiety (63% versus 17.4%; P < 0.01), or have supportive family/social environments (81.5% versus 34.8%; P < 0.01). Conclusions: The data support the validity of the PPC for matching comorbid patients. Mismatching increases no-show rates in general with undermatching, but it does so in particular with overmatching in patients with comorbid psychiatric symptomatology. Comorbidity interacts with gender, overmatched status, presence of anxiety, and supportive environment as predictors of treatment no-shows (odds ratios = 2.69, P < 0.05; 3.27, P < 0.05; 5.32, P < 0.001; and 3.12, P < 0.05, respectively). C1 [Angarita, Gustavo A.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA. [Angarita, Gustavo A.; Reif, Sharon; Pirard, Sandrine; Sharon, Estee; Gastfriend, David R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Addict Res Program, Dept Psychiat,W End House Clin, Boston, MA USA. [Reif, Sharon] Brandeis Univ, Heller Sch, Inst Behav Hlth, Waltham, MA 02254 USA. [Pirard, Sandrine] Univ Liege, Dept Psychiat, Liege, Belgium. [Gastfriend, David R.] Alkermes Inc, Cambridge, MA USA. RP Angarita, GA (reprint author), Yale Univ, Sch Med, Dept Psychiat, 300 George St, New Haven, CT 06511 USA. EM gustavo.angarita@yale.edu NR 37 TC 9 Z9 9 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1932-0620 J9 J ADDICT MED JI J. Addict. Med. PD JUN PY 2007 VL 1 IS 2 BP 79 EP 87 DI 10.1097/ADM.0b013e3180634c1d PG 9 WC Substance Abuse SC Substance Abuse GA 305GK UT WOS:000256165700005 PM 21768939 ER PT J AU Peluso, MAM Hatch, JP Glahn, DC Monkul, ES Sanches, M Najt, P Bowden, CL Barratt, ES Soares, JC AF Peluso, M. A. M. Hatch, J. P. Glahn, D. C. Monkul, E. S. Sanches, M. Najt, P. Bowden, C. L. Barratt, E. S. Soares, J. C. TI Trait impulsivity in patients with mood disorders SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE impulsivity; bipolar disorder; unipolar disorder; depression; mood ID BIPOLAR DISORDER; SUICIDE; HISTORY; SCALE AB Background: Impulsivity is a key component of the manic behavior of bipolar disorder and is reported to occur in bipolar patients as a stable characteristic, i.e. a trait. Nevertheless, impulsivity has not been widely studied in depressed bipolar patients. We assessed impulsivity in depressed and euthymic bipolar and unipolar patients and healthy controls. We hypothesized that bipolar subjects would have higher levels of trait impulsivity than the comparison groups. Methods: Twenty-four depressed bipolar, 24 depressed unipolar, 12 euthymic bipolar, and 10 euthymic unipolar patients, as well as 51 healthy subjects were evaluated with the Barratt Impulsiveness Scale (BIS). Analysis of covariance with age and sex as covariates was used to compare mean group differences. Results: Depressed bipolar, euthymic bipolar, and depressed unipolar patients did not differ, and showed greater impulsivity than healthy controls on all of the BIS scales. Euthymic unipolar patients scored higher than healthy controls only on motor impulsivity. Limitations: Higher number of past substance abusers in the bipolar groups, and no control for anxiety and personality disorders, as well as small sample sizes, limit the reach of this study. Conclusions: This study replicates prior findings of stable trait impulsivity in bipolar disorder patients, and extends them, confirming that this trait can be demonstrated in depressed patients, as well as manic and euthymic ones. Trait impulsivity may be the result of repeated mood episodes or be present prior to their onset, either way it would influence the clinical presentation of bipolar disorder. (c) 2006 Elsevier B.V. All rights reserved. C1 UTHSCSA, Dept Psychiat, San Antonio, TX USA. Univ Sao Paulo, Dept Psychiat, Sect Psychiat Epidemiol, Sao Paulo, Brazil. UTHSCSA, Dept Orthodont, San Antonio, TX USA. Dokuz Eylul Univ, Dept Psychiat, Izmir, Turkey. Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Med Branch, Dept Psychiat, Galveston, TX 77555 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. UTHSCSA, Dept Radiol, San Antonio, TX USA. RP Peluso, MAM (reprint author), Univ Sao Paulo, Inst Psychiat, Rua Dr Ovidio Pires Campos,785-3 Andar, BR-05403010 Sao Paulo, SP, Brazil. EM mampeluso@hotmail.com FU NCRR NIH HHS [M01-RR-01346]; NIMH NIH HHS [MH01736, MH068662] NR 18 TC 106 Z9 107 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUN PY 2007 VL 100 IS 1-3 BP 227 EP 231 DI 10.1016/j.jad.2006.09.037 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 185IK UT WOS:000247704400027 PM 17097740 ER PT J AU Schaechter, JD Connell, BD Stason, WB Kaptchuk, TJ Krebs, DE Macklin, EA Schnyer, RN Stein, J Scarborough, DM Parker, SW McGibbon, CA Wayne, PM AF Schaechter, Judith D. Connell, Brendan D. Stason, William B. Kaptchuk, Ted J. Krebs, David E. Macklin, Eric A. Schnyer, Rosa N. Stein, Joel Scarborough, Donna M. Parker, Stephen W. McGibbon, Chris A. Wayne, Peter M. TI Correlated change in upper limb function and motor cortex activation after verum and sham acupuncture in patients with chronic stroke SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID CORTICAL SURFACE; REHABILITATION; PLASTICITY; RECOVERY; TRIAL; PAIN; FMRI AB Background: Acupuncture may improve motor function in patients with chronic hemiparetic stroke, yet the neural mechanisms underlying such an effect are unknown. As part of a sham-controlled, randomized clinical trial testing the efficacy of a 10-week acupuncture protocol in patients with chronic hemiparetic stroke, we examined the relationship between changes in function of the affected upper limb and brain activation using functional magnetic resonance imaging (fMRI). Methods: Seven (7) chronic hemiparetic stroke patients underwent fMRI and testing of function of the affected upper limb (spasticity and range-of-motion) before and after a 10-week period of verum (N = 4) or sham (N = 3) acupuncture. The correlation between changes in function of the affected upper limb and brain activation after treatment was tested across patients. Results: We found a significant positive correlation between changes in function of the affected upper limb (spasticity and range of motion) and activation in a region of the ipsilesional motor cortex. Patients treated with verum acupuncture showed a trend toward a greater maximum activation change in this motor cortical area as compared to those treated with sham acupuncture. Conclusions: Acupuncture may improve function of the affected upper limb in chronic herniparetic stroke patients by increasing activity in the ipsilesional motor cortex. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Osher Inst, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biomot Lab, Boston, MA USA. New England Res Inst, Watertown, MA 02172 USA. New England Sch Acupuncture, Watertown, MA USA. Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ New Brunswick, Inst Biomed Engn, Federicton, NB, Canada. RP Schaechter, JD (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 13th St,Bldg 149,Room 2301, Charlestown, MA 02129 USA. EM judith@nmr.mgh.harvard.edu RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 22 TC 31 Z9 42 U1 1 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JUN PY 2007 VL 13 IS 5 BP 527 EP 532 DI 10.1089/acm.2007.6316 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 183LU UT WOS:000247575100007 PM 17604556 ER PT J AU Melanson, SEF Lewandrowski, EL Griggs, DA Flood, JG AF Melanson, Stacy E. F. Lewandrowski, Elizabeth Lee Griggs, David A. Flood, James G. TI Interpreting tricyclic antidepressant measurements in urine in an emergency department setting: Comparison of two qualitative point-of-care urine tricyclic antidepressant drug immunoassays with quantitative serum chromatographic analysis SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID SCREEN C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Div Clin Labs, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Flood, JG (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRI 5, Boston, MA 02114 USA. EM jflood@partners.org NR 12 TC 14 Z9 14 U1 0 U2 1 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JUN PY 2007 VL 31 IS 5 BP 270 EP 275 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 179MY UT WOS:000247295200004 PM 17579971 ER PT J AU Bamman, MM Petrella, JK Kim, JS Mayhew, DL Cross, JM AF Bamman, Marcas M. Petrella, John K. Kim, Jeong-su Mayhew, David L. Cross, James M. TI Cluster analysis tests the importance of myogenic gene expression during myofiber hypertrophy in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE muscle growth; myogenin; insulin-like growth factor I; muscle fiber ID GROWTH-FACTOR-I; MUSCLE SATELLITE CELLS; HUMAN SKELETAL-MUSCLE; MESSENGER-RNA EXPRESSION; IGF-I; RESISTANCE EXERCISE; MOLECULAR RESPONSES; TIME-COURSE; OLDER MEN; NITRIC-OXIDE AB We applied K-means cluster analysis to test the hypothesis that muscle-specific factors known to modulate protein synthesis and satellite cell activity would be differentially expressed during progressive resistance training (PRT, 16 wk) in 66 human subjects experiencing extreme, modest, and failed myofiber hypertrophy. Muscle mRNA expression of IGF-I isoform Ea (IGF-IEa), mechanogrowth factor (MGF, IGF-IEc), myogenin, and MyoD were assessed in muscle biopsies collected at baseline (T1) and 24 h after the first (T2) and last (T3) loading bouts from previously untrained subjects clustered as extreme responders (Xtr, n = 17), modest responders (Mod, n = 32), and nonresponders (Non, n = 17) based on mean myofiber hypertrophy. Myofiber growth averaged 2,475 mu m(2) in Xtr, 1, 111 mu m(2) in Mod, and - 16 mu m(2) in Non. Main training effects revealed increases in all transcripts (46-83%, P < 0.005). For the entire cohort, IGF-IEa. MGF, and myogenin mRNAs were upregulated by T2 (P < 0.05), while MyoD did not increase significantly until T3 (P < 0.001). Within clusters, MGF and myogenin upregulation was robust in Xtr (126% and 65%) and Mod (73% and 41%) vs. no changes in Non. While significant in all clusters by T3, IGF-IEa increased most in Xtr (105%) and least in Non (44%). Although MyoD expression increased overall, no changes within clusters were detected. We reveal for the first time that MGF and myogenin transcripts are differentially expressed in subjects experiencing varying degrees of PRT-mediated myofiber hypertrophy. The data strongly suggest the load-mediated induction of these genes may initiate important actions necessary to promote myofiber growth during PRT, while the role of MyoD is less clear. C1 Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Med Sci Training Program, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA. RP Bamman, MM (reprint author), Univ Alabama, Vet Affairs Med Ctr, Dept Physiol & Biophys, Core Muscle Res Lab, GRECC-11G,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mbamman@uab.edu FU NCRR NIH HHS [M01-RR-00032]; NIA NIH HHS [R01-AG-017896] NR 49 TC 76 Z9 77 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUN PY 2007 VL 102 IS 6 BP 2232 EP 2239 DI 10.1152/japplphysiol.00024.2007 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 195KJ UT WOS:000248410800023 PM 17395765 ER PT J AU Estok, DM Burroughs, BR Muratoglu, OK Harris, WH AF Estok, Daniel M., II Burroughs, Brian R. Muratoglu, Orhun K. Harris, William H. TI Comparison of hip simulator wear of 2 different highly cross-linked ultra high molecular weight polyethylene acetabular components using both 32-and 38-mm femoral heads SO JOURNAL OF ARTHROPLASTY LA English DT Article DE UHMWP; total hip arthroplasty; femoral head size ID CRACK PROPAGATION RESISTANCE; ARTHROPLASTY; UHMWPE; REPLACEMENTS; SOCKETS; LARGER; MOTION; RATES; CUPS AB Much evidence Suggests that ultra high molecular weight polyethylene (UHMWP) irradiated to 9.5 Mrad has lower wear than UHMWP given 5 Mrad. Curiously, highly cross-linked polyethylenes gain weight during hip simulator testing. We postulated that (a) UHMWP irradiated to 9.5 Mrad would wear less than UHMWP irradiated to 5 Mrad UHMWP, (b) articulation against 38-mm heads would accentuate this difference, and (c) weight gain of highly cross-linked material reflects the inadequacy of load soak controls. We compared 9.5 versus 5 Mrad polyethylene ill hip simulator wear tests, with both load soak corrections and with novel "motion soak" corrections. The 9.5-Mrad material wore less than 5-Mrad material for 32- and 38-mm heads. Motion soak corrections were more accurate than load soak corrections. C1 Massachusetts Gen Hosp, Total Joint Outcomes Lab, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Total Joint Outcomes Lab, Harris Orthopaed Biomech & Biomat Lab, 55 Fruit St, GRJ 1126, Boston, MA 02114 USA. NR 31 TC 19 Z9 21 U1 1 U2 5 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 JUN PY 2007 VL 22 IS 4 BP 581 EP 589 DI 10.1016/j.arth.2006.07.009 PG 9 WC Orthopedics SC Orthopedics GA 183WO UT WOS:000247603300016 PM 17562417 ER PT J AU Orban, T Kis, J Szereday, L Engelmann, P Farkas, K Jalahej, H Treszl, A AF Orban, Tihamer Kis, Janos Szereday, Laszlo Engelmann, Peter Farkas, Klara Jalahej, Heyam Treszl, Andras TI Reduced CD4+ T-cell-specific gene expression in human type I diabetes mellitus SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE type 1 diabetes mellitus; CD4+cells; DNA microarray ID PRIMARY IMMUNE-RESPONSE; GAMMA CHAIN GAMMA(C); INTERFERON-GAMMA; MOUSE; LYMPHOCYTES; INSULITIS; PANCREAS; CLONES; MICE; AUTOANTIGENS AB Type 1 diabetes mellitus (T1DM) in humans is characterized by the T-cell-dependent destruction of the insulin producing pancreatic beta cells; however, the precise pathogenesis of the disease, especially the initiation of pathologic immune response, is still largely unknown. We hypothesized that the function of human CD4+ T cells is altered in T1DM and analyzed unstimulated human peripheral blood CD4+ T-cell gene expression. We used a novel three-way comparison of DNA microarray data of CD4+ T cells isolated from patients with new onset T1DM, patients with long-term Type 2 diabetes (T2DM), and from healthy control subjects in order to eliminate any possible influence of glucose homeostasis on our findings. We analyzed the T1DM specific gene-expression changes and their functional relevance to T1DM autoimmunity. Our genetic and functional data show that T1DM CD4+ T cells are down-regulated specifically affecting key immune functions and cell cycle. Histone deacetylase gene expression, a key regulator of epigenetic modification is also reduced. The CD4+ T cells showed impaired function, including an abnormal immune response, which may be a key element that leads to the breakdown of self-tolerance. (C) 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. Polyclin Hospitaller Brothers, Dept Internal Med & Gastroenterol, H-1027 Budapest, Hungary. Hungarian Acad Sci, Reprod & Tumor Immunol Res Grp, H-7643 Pecs, Hungary. Hungarian Acad Sci, Fac Med, Dept Immunol & Biotechnol, H-7643 Pecs, Hungary. Bajcsy Zsilinsky Hosp, Dept Med 3, H-1106 Budapest, Hungary. Semmelweis Univ, Dept Paediat 1, H-1085 Budapest, Hungary. RP Orban, T (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02115 USA. EM torban@joslin.harvard.edu; janos.kis@joslin.harvard.edu; laszlo.szereday@aok.pte.hu; peter.engelmann@joslin.harvard.edu; klara.farkas@joslin.harvard.edu; treszl@gyer1.sote.hu NR 48 TC 21 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 2007 VL 28 IS 4 BP 177 EP 187 DI 10.1016/j.jaut.2007.01.002 PG 11 WC Immunology SC Immunology GA 185PV UT WOS:000247723800002 PM 17320348 ER PT J AU Gwack, Y Srikanth, S Feske, S Cruz-Guilloty, F Oh-hora, M Neems, DS Hogan, PG Rao, A AF Gwack, Yousang Srikanth, Sonal Feske, Stefan Cruz-Guilloty, Fernando Oh-hora, Masatsugu Neems, Daniel S. Hogan, Patrick G. Rao, Anjana TI Biochemical and functional characterization of Orai proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OPERATED CA2+ ENTRY; PLASMA-MEMBRANE; CHANNEL FUNCTION; CALCIUM-ENTRY; CRAC CHANNEL; CENTRAL-SPINDLE; T-LYMPHOCYTES; RNAI SCREEN; STIM1; STORE AB Stimulation of immune cells triggers Ca2+ entry through store-operated Ca2+ release-activated Ca2+ channels, promoting nuclear translocation of the transcription factor NFAT. Through genome-wide RNA interference screens in Drosophila, we and others identified olf186-F (Drosophila Orai, dOrai) and dStim as critical components of store-operated Ca2+ entry and showed that dOrai and its human homologue Orai1 are pore subunits of the Ca2+ release-activated Ca2+ channel. Here we report that Orai1 is predominantly responsible for store-operated Ca2+ influx in human embryonic kidney 293 cells and human T cells and fibroblasts, although its paralogue Orai3 can partly compensate in the absence of functional Orai1. All three mammalian Orai are widely expressed at the mRNA level, and all three are incorporated into the plasma membrane. In human embryonic kidney 293 cells, Orai1 is glycosylated at an asparagine residue in the predicted second extracellular loop, but mutation of the residue does not compromise function. STIM1 and Orai1 colocalize after store depletion, but Orai1 does not associate detectably with STIM1 in glycerol gradient centrifugation or coimmunoprecipitation experiments. Glutamine substitutions in two conserved glutamate residues, located within predicted transmembrane helices of Drosophila Orai and human Orai1, greatly diminish store-operated Ca2+ influx, and primary T cells ectopically expressing mutant E106Q and E190Q Orai1 proteins show reduced proliferation and cytokine secretion. Together, these data establish Orai1 as a predominant mediator of store-operated calcium entry, proliferation, and cytokine production in T cells. C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Rm 152,Warren Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu OI Feske, Stefan/0000-0001-5431-8178 FU NIAID NIH HHS [AI066128, AI40127]; NIGMS NIH HHS [GM075256] NR 34 TC 217 Z9 222 U1 2 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2007 VL 282 IS 22 BP 16232 EP 16243 DI 10.1074/jbc.M609630200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 172HH UT WOS:000246794300031 PM 17293345 ER PT J AU Fernandes, ND Sun, YL Price, BD AF Fernandes, Norvin D. Sun, Yingli Price, Brendan D. TI Activation of the kinase activity of ATM by retinoic acid is required for CREB-dependent differentiation of neuroblastoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE RESPONSE; NEURON-LIKE CELLS; ATAXIA-TELANGIECTASIA; NEUROTROPHIC FACTOR; SH-SY5Y CELLS; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; SYNAPTIC CAPTURE; GENE-EXPRESSION; PROTEIN-KINASE AB The ATM protein kinase is mutated in ataxia telangiectasia, a genetic disease characterized by defective DNA repair, neurodegeneration, and growth factor signaling defects. The activity of ATM kinase is activated by DNA damage, and this activation is required for cells to survive genotoxic events. In addition to this well characterized role in DNA repair, we now demonstrate a novel role for ATM in the retinoic acid ( RA)induced differentiation of SH-SY5Y neuroblastoma cells into post-mitotic, neuronal-like cells. RA rapidly activates the activity of ATM kinase, leading to the ATM-dependent phosphorylation of the CREB protein, extrusion of neuritic processes, and differentiation of SH-SY5Y cells into neuronal-like cells. When ATM protein expression was suppressed by short hairpin RNA, the ATM-dependent phosphorylation of CREB was blocked. Furthermore, ATM-negative cells failed to differentiate into neuronal-like cells when exposed to retinoic acid; instead, they underwent cell death. Expression of a constitutively active CREBVP16 construct, or exposure to forskolin to induce CREB phosphorylation, rescued ATM negative cells and restored differentiation. Furthermore, when dominant negative CREB proteins with mutations in either the CREB phosphorylation site (CREBS133A) or the DNA binding domain (KCREB) were introduced into SH-SY5Y cells, retinoic acid-induced differentiation was blocked and the cells underwent cell death. The results demonstrate that ATM is required for the retinoic acid-induced differentiation of SH-SY5Y cells through the ATM dependent-phosphorylation of serine 133 of CREB. These results therefore define a novel mechanism for activation of the activity of ATM kinase by RA, and implicate ATM in the regulation of CREB function during RA-induced differentiation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, JF 516, Boston, MA 02115 USA. EM brendan_price@dfci.harvard.edu FU NCI NIH HHS [CA64585, CA93602, T32 CA09078]; NIAID NIH HHS [U19AI067751] NR 51 TC 24 Z9 24 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 1 PY 2007 VL 282 IS 22 BP 16577 EP 16584 DI 10.1074/jbc.M609628200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 172HH UT WOS:000246794300064 PM 17426037 ER PT J AU Sah, AP Geller, DS Mankin, HJ Rosenberg, AE DeLaney, TF Wright, CD Hornicek, FJ AF Sah, Alexander P. Geller, David S. Mankin, Henry J. Rosenberg, Andrew E. DeLaney, Thomas F. Wright, Cameron D. Hornicek, Francis J. TI Malignant transformation of synovial chondromatosis of the shoulder to chondrosarcoma - A case report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SOFT-TISSUE TUMORS; STERNOCLAVICULAR JOINT; FLOW-CYTOMETRY; KNEE; OSTEOCHONDROMATOSIS; CHONDROMETAPLASIA; PROLIFERATION; CARTILAGE; SECONDARY; HIP C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cartilage Biol & Orthopaed Oncol Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA. RP Sah, AP (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM asah@partners.org NR 56 TC 18 Z9 19 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUN PY 2007 VL 89A IS 6 BP 1321 EP 1328 DI 10.2106/JBJS.F.00511 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 176LE UT WOS:000247085800022 PM 17545437 ER PT J AU Yeon, HB Kaplan, FS Shore, EM Rosenberg, AE Jupiter, JB AF Yeon, Howard B. Kaplan, Frederick S. Shore, Eileen M. Rosenberg, Andrew E. Jupiter, Jesse B. TI Focal fibronodular heterotopic ossification - A case report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID JUVENILE HYALINE FIBROMATOSIS; PROGRESSIVE OSSEOUS HETEROPLASIA; PROTEUS SYNDROME; NATURAL-HISTORY; FIBRODYSPLASIA; DISORDER; PHENOTYPE; MUTATIONS; FEATURES; PATIENT C1 Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Yawkey Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. Univ Penn, Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. RP Yeon, HB (reprint author), Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. RI Shore, Eileen/D-2593-2009 NR 30 TC 1 Z9 1 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JUN PY 2007 VL 89A IS 6 BP 1329 EP 1336 DI 10.2106/JBJS.E.01386 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 176LE UT WOS:000247085800023 PM 17545438 ER PT J AU Mangat, S Agarwal, S Rosendorff, C AF Mangat, Simardeep Agarwal, Sanjay Rosendorff, Clive TI Do statins lower blood pressure? SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Review DE statins; hypertension; blood pressure ID NITRIC-OXIDE SYNTHASE; COA REDUCTASE INHIBITORS; LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE CELLS; PLACEBO-CONTROLLED TRIAL; TYPE-2 DIABETIC-PATIENTS; CHOLESTEROL REDUCTION; HYPERTENSIVE PATIENTS; ENDOTHELIAL-CELLS; OXIDIZED LDL AB Hypercholesterolemia is present in many patients with hypertension and adds a significant component of cardiovascular risk. The 3-hydroxy-3 methyl-glutaryl-coenzyme A reductase inhibitors (statins) lower low-density lipoprotein cholesterol but also inhibit many of the structural and functional components of the arteriosclerotic process. Structural effects include reductions in vascular smooth muscle hypertrophy and proliferation, fibrin deposition, and collagen cross-linking. Among the functional effects are improvements in endothelial function, reduction in inflammatory cytokines and reactive oxygen species, and down-regulation of angiotensin 11 and endothelin receptors. These would be expected to reduce blood pressure in patients with hypertension; 14 studies have shown statin-induced decrease in blood pressure, but I I studies showed no effect. Many of the studies had no placebo controls, were of short duration, or had small sample sizes, or combinations of these. Despite predictions made on the basis of. the vasoprotective actions of statins, the blood-pressure-lowering effects of statins are at best modest. C1 James J Peters VA Med Ctr, Dept Med 111, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. James J Peters VA Med Ctr, Bronx, NY USA. RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, Dept Med 111, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@med.va.gov NR 67 TC 13 Z9 13 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD JUN PY 2007 VL 12 IS 2 BP 112 EP 123 DI 10.1177/107424807300380 PG 12 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 176VF UT WOS:000247112300004 PM 17562781 ER PT J AU Smirnakis, SM Schmid, MC Weber, B Tolias, AS Augath, M Logothetis, NK AF Smirnakis, Stelios M. Schmid, Michael C. Weber, Bruno Tolias, Andreas S. Augath, Mark Logothetis, Nikos K. TI Spatial specificity of BOLD versus cerebral blood volume fMRI for mapping cortical organization SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE monkey; fMRI (functional magnetic resonance imaging); MION (monocrystalline iron oxide nanoparticles); BOLD (blood oxygen level dependent signal); CBV (cerebral blood volume); spatial (specificity) ID RAT FOREPAW STIMULATION; HUMAN VISUAL-CORTEX; FUNCTIONAL MRI; LAMINAR SPECIFICITY; COLUMNAR RESOLUTION; NEURONAL-ACTIVITY; OCULAR DOMINANCE; CONTRAST AGENT; STRIATE CORTEX; MACAQUE MONKEY AB Intravascular contrast agents are used in functional magnetic resonance imaging to obtain cerebral blood volume (CBV) maps of cortical activity. Cerebral blood volume imaging with MION (monocrystalline-iron-oxide-nanoparticles) increases the sensitivity of functional imaging compared with the blood oxygenation level-dependent (BOLD) signal (Leite et al, 2002; Mandeville et al, 1998; Vanduffel et al, 2001). It therefore represents an attractive method for obtaining detailed maps of cortical organization (Vanduffel et al, 2001; Zhao et al, 2005). However, it remains to be determined how the spatial profile of CBV maps of cortical activity derived with MION compares with the profile of BOLD activation maps under a variety of different stimulation conditions. We used several stimulation paradigms to compare the spatial specificity of CBV versus BOLD activation maps in macaque area V1 at 4.7 T. We observed that: (1) CBV modulation is relatively stronger in deep cortical layers compared with BOLD, in agreement with studies in cats (Harel et al, 2006) and rodents (Lu et al, 2004; Mandeville and Marota, 1999) and (2) surprisingly, under large surround stimulation conditions, CBV maps extend along the cortical surface to cover large ( > 10mm) regions of the cortex that are devoid of significant BOLD modulation. We conclude that the spatial profiles of BOLD and CBV activity maps do not coregister across all stimulus conditions, and therefore do not necessarily represent equivalent transforms of the neural response. Cerebral blood volume maps should be interpreted with care, in the context of the particular experimental paradigm applied. C1 Max Planck Inst Biol Cybernet, Tubingen, Germany. Harvard Univ, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Smirnakis, SM (reprint author), Harvard Univ, Dept Neurol, Brigham & Womens Hosp, 75 Francis St,Room SR-171D, Boston, MA 02115 USA. EM smsmirnakis@partners.org RI Schmid, Michael/G-1867-2010; Weber, Bruno/E-4400-2013 OI Schmid, Michael/0000-0003-1424-130X; NR 40 TC 41 Z9 42 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2007 VL 27 IS 6 BP 1248 EP 1261 DI 10.1038/sj.jcbfm.9600434 PG 14 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 171GL UT WOS:000246723300015 PM 17213863 ER PT J AU Huppert, TJ Allen, MS Benav, H Jones, PB Boas, DA AF Huppert, Theodore J. Allen, Monica S. Benav, Heval Jones, Phill B. Boas, David A. TI A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CBF and oxidative metabolism; human and experimental studies; hemodynamics; optical imaging and spectroscopy; NIRS (near-infrared spectroscopy); MRI hemodynamics ID RAT SOMATOSENSORY CORTEX; BLOOD-FLOW; HEMODYNAMIC-RESPONSE; NEURONAL-ACTIVITY; LASER-DOPPLER; BRAIN; ACTIVATION; DYNAMICS; DELIVERY; TISSUE AB Functional hemodynamic responses are the composite results of underlying variations in cerebral oxygen consumption and the dilation of arterial vessels after neuronal activity. The development of biophysically based models of the cerebral vasculature allows the separation of the neuro- metabolic and neuro- vascular influences on measurable hemodynamic signals such as functional magnetic resonance imaging or optical imaging. We describe a multicompartment model of the vascular and oxygen transport dynamics associated with stimulus- driven neuronal activation. Our model offers several unique features compared with previous formulations such as the ability to estimate baseline blood flow, volume, and oxygen consumption from functional data. In addition, we introduce a capillary compliance model, arterial and venous oxygen permeability, and model the dynamics of extravascular tissue oxygenation. We apply this model to multimodal optical spectroscopic and laser speckle imaging of the rat somato- sensory cortex during nine conditions of whisker stimulation. By fitting the model using a psuedo- Bayesian framework to incorporate multimodal observations, we estimate baseline blood flow to be 94 (+/- 15) mL/ 100 g min and baseline oxygen consumption to be 6.7 ( +/- 1.3) mL O-2/100 g min. We calculate parametric, linear increases in arterial dilation ( R-2 = 0.96) and CMRO2 ( R-2 = 0.87) responses over the nine conditions. Other parameters estimated by the model include vascular transit time and volume reserve, oxygen content, saturation, diffusivity rate constants, and partial pressure of oxygen in the vascular compartments and in the extravascular tissue. Finally, we compare this model to earlier work and find that the multicompartment model more accurately describes the observed oxygenation changes when compared with a single compartment version. C1 Harvard Univ, Grad Programs Biophys, Boston, MA 02115 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Univ Texas, Dept Elect Engn, Arlington, TX 76019 USA. RP Huppert, TJ (reprint author), Harvard Univ, Grad Programs Biophys, Boston, MA 02115 USA. EM thuppert@nmr.mgh.harvard.edu OI Jones, Phillip/0000-0003-0525-6323 FU NCRR NIH HHS [P41 RR014075, P41 RR014075-106000, P41-RR14075]; NIBIB NIH HHS [EB000790, R01 EB000790, R01 EB000790-05, R01 EB001954, R01 EB001954-07, R01 EB002482, R01 EB002482-05, R01-EB001954, R01-EB002482] NR 40 TC 54 Z9 55 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2007 VL 27 IS 6 BP 1262 EP 1279 DI 10.1038/sj.jcbfm.9600435 PG 18 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 171GL UT WOS:000246723300016 PM 17200678 ER PT J AU Mitra, R Fleischmann, K AF Mitra, Raj Fleischmann, Katharine TI Management of the sheared epidural catheter: is surgical extraction really necessary? SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE epidural catheter removal ID LUMBAR EXTRADURAL CATHETERS; COMPUTED-TOMOGRAPHY; WITHDRAWAL FORCES; REMOVAL; INFUSION; MORPHINE; FRAGMENT AB Trauma to epidural catheters on insertion or removal may result in shearing or breakage. Although there is no evidence of neurologic sequelae from a sheared catheter, many reports still advocate eventual surgical removal. The literature suggests the following options: (1) using slow continuous force at all times; (2) discontinuing application of force if the catheter begins to stretch and reapplying traction several hours later; (3) placing of the patient in the same position as insertion; (4) placing the patient in the lateral decubitus position if possible; (5) attempting to remove in extreme flexion if the previous interventions are not efficacious; (6) attempting extension if flexion fails; (7) attempting removal after injection of preservative-free normal saline through the catheter; (8) considering use of a convex surgical frame; (9) considering computed tomographic scan to identify the etiology of entrapment; (10) considering leaving a retained epidural catheter in place in adult patients; (11) providing patient education regarding "red flags" to watch out for; and (12) neurosurgical consultation for all cases in which the catheter fragment is in the spinal canal. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Pain Management Ctr, Boston, MA 02114 USA. RP Mitra, R (reprint author), Stanford Univ, Med Ctr, Dept Orthoped Surg, Stanford Intervent Spine Ctr, Stanford, CA 94305 USA. EM rmitra@stanford.edu NR 33 TC 34 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD JUN PY 2007 VL 19 IS 4 BP 310 EP 314 DI 10.1016/j.jclinane.2006.11.005 PG 5 WC Anesthesiology SC Anesthesiology GA 184PM UT WOS:000247654000016 PM 17572331 ER PT J AU Misra, M Miller, KK Cord, J Prabhakaran, R Herzog, DB Goldstein, M Katzman, DK Klibanski, A AF Misra, Madhusmita Miller, Karen K. Cord, Jennalee Prabhakaran, Rajani Herzog, David B. Goldstein, Mark Katzman, Debra K. Klibanski, Anne TI Relationships between serum adipokines, insulin levels, and bone density in girls with anorexia nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MAPK SIGNALING PATHWAY; ADOLESCENT GIRLS; SECRETORY DYNAMICS; HEALTHY ADOLESCENTS; HUMAN OSTEOBLASTS; MINERAL DENSITY; BULIMIA-NERVOSA; GROWTH-HORMONE; ADIPONECTIN; LEPTIN AB Background: Adolescents with anorexia nervosa ( AN) have low bone mineral density (BMD). Adipokines and insulin play an important role in bone metabolism in healthy individuals. However, their association with bone metabolism in AN is unknown. Objective: The aim of the study was to determine whether adipokines and insulin are independently associated with measures of BMD in adolescents with AN and controls. Design/Methods: Levels of adiponectin and insulin, fasting and after oral glucose, were evaluated in 17 AN patients and 19 controls (age, 12-18 yr), in whom hormonal parameters [GH, IGF-I, cortisol, estradiol, leptin, ghrelin, and peptide YY (PYY)] had been previously determined. Body composition, bone mineral content, and BMD at the lumbar spine, hip, femoral neck, and total body were assessed by dual energy x-ray absorptiometry. Two bone formation and bone resorption markers were examined. Setting: The study was conducted at a General Clinical Research Center. Results: Adiponectin differed between AN subjects and controls after controlling for fat mass and decreased in both after oral glucose (P = 0.02 and 0.07). On regression modeling, independent associations were observed of: 1) body mass index and adiponectin with lumbar spine bone mineral apparent density Z-scores (r(2) = 0.45); 2) lean mass, PYY, and ghrelin with hip Z- scores (r(2) = 0.55); 3) adiponectin and lean mass with femoral neck-bone mineral apparent density Z- scores (r(2) = 0.34); and 4) lean mass, PYY, GH, and ghrelin with total body-bone mineral content/height Z- scores (r(2) = 0.64), for the combined group. Adiponectin was also independently associated with BMD, and insulin was associated with bone turnover markers in the groups considered separately. Conclusions: Adiponectin contributes significantly to the variability of bone density, and insulin contributes to bone turnover markers in adolescent girls. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harris Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp Children, Div Adolescent Med, Boston, MA 02114 USA. Hosp Sick Children, Dept Pediat, Div Adolescent Med, Toronto, ON M5G 1X8, Canada. RP Misra, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM mmisra@partners.org FU NCRR NIH HHS [K23 RR018851, M01 RR01066]; NIDDK NIH HHS [DK062249] NR 40 TC 91 Z9 95 U1 0 U2 2 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 JUN PY 2007 VL 92 IS 6 BP 2046 EP 2052 DI 10.1210/jc.2006-2855 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 176CX UT WOS:000247061700011 PM 17356044 ER PT J AU de Nanclares, GP Fernandez-Rebollo, E Santin, I Garcia-Cuartero, B Gaztambide, S Menendez, E Morales, MJ Pombo, M Bilbao, JR Barros, F Zazo, N Ahrens, W Juppner, H Hiort, O Castano, L Bastepe, M AF de Nanclares, Guiomar Perez Fernandez-Rebollo, Eduardo Santin, Izortze Garcia-Cuartero, Beatriz Gaztambide, Sonia Menendez, Edelmiro Morales, Maria Jose Pombo, Manuel Bilbao, Jose Ramon Barros, Francisco Zazo, Nuria Ahrens, Wiebke Jueppner, Harald Hiort, Olaf Castano, Luis Bastepe, Murat TI Epigenetic defects of GNAS in patients with pseudohypoparathyroidism and mild features of Albright's hereditary osteodystrophy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IMPRINTING CONTROL ELEMENT; GENE; IB; PROTEIN; DELETION AB Context: Several endocrine disorders that share resistance to PTH are grouped under the term pseudohypoparathyroidism (PHP). PHP type I, associated with blunted PTH-induced nephrogenous cAMP formation and phosphate excretion, is subdivided according to the presence or absence of additional endocrine abnormalities, Albright's hereditary osteodystrophy (AHO), and reduced Gs alpha activity caused by GNAS mutations. Objective: We sought to identify the molecular defect in four unrelated patients who were thought to have PHP-Ia because of PTH and TSH resistance and mild AHO features. Methods: Gs alpha activity and mutation analysis, and assessment of GNAS haplotype, methylation, and gene expression were performed for probands and family members. Results: Two patients showed modest decreases in erythrocyte Gs alpha activity. Instead of Gs alpha point mutations, however, all four patients showed methylation defects of the GNAS locus, a feature previously described only for PHP-Ib. Furthermore, one patient with an isolated loss of GNAS exon A/ B methylation had the 3-kb STX16 deletion frequently identified in PHP-Ib patients. In all but one of the remaining patients, haplotype analysis excluded large deletions or uniparental disomy as the cause of the observed methylation changes. Conclusions: Our investigations indicate that an overlap may exist between molecular and clinical features of PHP-Ia and PHP-Ib. No current mechanisms can explain the AHO-like features of our patients, some of which may not be linked to GNAS. Therefore, patients with hormone resistance and AHO-like features in whom coding Gs alpha mutations have been excluded should be evaluated for epigenetic alterations within GNAS. C1 Hosp Cruces, Endocrinol & Diabet Res Unit, E-48903 Baracaldo, Basque Country, Spain. Severo Ochoa Hosp, Pediat Endocrinol Unit, Madrid 28911, Spain. Univ Basque Country, Dept Med, Leioa 48940, Bizkaia, Spain. Univ Basque Country, Dept Nursing, Leioa 48940, Bizkaia, Spain. Univ Basque Country, Dept Pediat, Leioa 48940, Bizkaia, Spain. Hosp Navarra, Serv Endocrinol, Pamplona 31080, Spain. Hosp Meixoeiro, Serv Endocrinol, Viga 36200, Pontevedra, Spain. Clin Univ Santiago de Compostela, Pediat Endocrinol Growth & Adolescent Unit, Santiago De Compostela 15706, A Coruna, Spain. Fdn Publ Galega Med Xenom, Santiago De Compostela 15706, A Coruna, Spain. Univ Lubeck, Dept Pediat & Adolescent Med, D-23538 Lubeck, Germany. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Castano, L (reprint author), Hosp Cruces, Endocrinol & Diabet Res Grp, E-48903 Bizkaia, Basque Country, Spain. EM lcastano@hcru.osakidetza.net; bastepe@helix.mgh.harvard.edu RI Gaztambide, Sonia/E-1760-2012; Bilbao, Jose Ramon/A-9177-2008; Menendez Torre, Edelmiro/G-1547-2013; Santin, Izortze/C-3034-2014; Castano, Luis/C-3084-2009 OI Bilbao, Jose Ramon/0000-0002-3176-501X; Menendez Torre, Edelmiro/0000-0002-9548-7821; SANTIN, IZORTZE/0000-0003-1651-6776; FU NIDDK NIH HHS [K01 DK062973]; PHS HHS [R01 46718-10] NR 20 TC 89 Z9 90 U1 0 U2 2 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 JUN PY 2007 VL 92 IS 6 BP 2370 EP 2373 DI 10.1210/jc.2006.2287 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 176CX UT WOS:000247061700061 PM 17405843 ER PT J AU Volandes, AE Abbo, ED AF Volandes, Angelo E. Abbo, Elmer D. TI Flipping the default: A novel approach to cardiopulmonary resuscitation in end-stage dementia SO JOURNAL OF CLINICAL ETHICS LA English DT Review ID NURSING-HOME RESIDENTS; LIFE-SUSTAINING TREATMENTS; SURROGATE DECISION-MAKING; SERIOUSLY ILL PATIENTS; PERCUTANEOUS ENDOSCOPIC GASTROSTOMY; RANDOMIZED CONTROLLED TRIAL; INTENSIVE-CARE-UNIT; ADVANCE DIRECTIVES; OF-LIFE; ELDERLY PATIENTS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Unit, Boston, MA USA. RP Volandes, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Unit, Boston, MA USA. EM avolandes@partners.org; eabbo@medicine.bsd.uchicago.edu NR 128 TC 8 Z9 8 U1 4 U2 7 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SUM PY 2007 VL 18 IS 2 BP 122 EP 139 PG 18 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 191XX UT WOS:000248166400004 PM 17682620 ER PT J AU Garibyan, L Lobito, AA Siegel, RM Call, ME Wucherpfennig, KW Geha, RS AF Garibyan, Lilit Lobito, Adrian A. Siegel, Richard M. Call, Matthew E. Wucherpfennig, Kai W. Geha, Raif S. TI Dominant-negative effect of the heterozygous C104R TACI mutation in common variable immunodeficiency (CVID) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CRYSTAL-STRUCTURE; B-CELLS; RECEPTOR; APRIL; ACTIVATION; BAFF; COMPLEX; BINDING; BLYS; IDENTIFICATION AB B cells from patients with common variable immunodeficiency (CVID) who are heterozygous for transmembrane activator and CAML interactor (TACT) mutation C104R, which abolishes ligand binding, fail to produce Igs in response to TACT ligand. It is not known whether this is due to haploinsufficiency or dominant interference. Using in vitro transfection assays, here we demonstrate that C104R and the corresponding murine TACT mutant, C76R, which also does not bind ligand, dominantly interfere with TACT signaling. This effect was dependent on preassociation of the mutants with WT TACT in the absence of ligand. The mutants did not interfere with ligand binding by WT TACT, suggesting that they may act by disrupting ligand-induced receptor rearrangement and signaling. This work demonstrates that TACT preassembles as an oligomeric complex prior to ligand binding and provides a mechanistic insight into how the heterozygous C104R TACT mutation can potentially lead to CVID. C1 Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. NIAMSD, Immunoregulat Unit, NIH, Bethesda, MD USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA USA. RP Geha, RS (reprint author), Childrens Hosp, Div Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu OI Call, Matthew/0000-0001-5846-6469 FU NIAID NIH HHS [T32 AI007512, T32-AI-007512, P01 AI031541, P01-AI-031541, R01 AI054520] NR 27 TC 57 Z9 58 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 JUN PY 2007 VL 117 IS 6 BP 1550 EP 1557 DI 10.1172/JCI31023 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 175ZJ UT WOS:000247052200014 PM 17492055 ER PT J AU Wang, Y Wan, C Deng, LF Liu, XM Cao, XM Gilbert, SR Bouxsein, ML Faugere, MC Guldberg, RE Gerstenfeld, LC Haase, VH Johnson, RS Schipani, E Clemens, TL AF Wang, Ying Wan, Chao Deng, Lianfu Liu, Ximeng Cao, Xuemei Gilbert, Shawn R. Bouxsein, Mary L. Faugere, Marie-Claude Guldberg, Robert E. Gerstenfeld, Louis C. Haase, Volker H. Johnson, Randall S. Schipani, Ernestina Clemens, Thomas L. TI The hypoxia-inducible factor a pathway couples angiogenesis to osteogenesis during skeletal development SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LINDAU TUMOR-SUPPRESSOR; VASCULAR CONTRIBUTION; EPIPHYSIAL CARTILAGE; O-2 HOMEOSTASIS; FACTOR 1-ALPHA; FACTOR-I; CELLS; BONE; GENE; GROWTH AB Skeletal development and turnover occur in close spatial and temporal association with angiogenesis. Osteoblasts are ideally situated in bone to sense oxygen tension and respond to hypoxia by activating the hypoxia-inducible factor a (HIF alpha.) pathway. Here we provide evidence that HIF alpha promotes angiogenesis and osteogenesis by elevating VEGF levels in osteoblasts. Mice overexpressing HIF alpha. in osteoblasts through selective deletion of the von Hippel-Lindau gene (Vhl) expressed high levels of Vegf and developed extremely dense, heavily vascularized long bones. By contrast, mice lacking Hifla in osteoblasts had the reverse skeletal phenotype of that of the Vhl mutants: long bones were significantly thinner and less vascularized than those of controls. Loss of Vhl in osteoblasts increased endothelial sprouting from the embryonic metatarsals in vitro but had little effect on osteoblast function in the absence of blood vessels. Mice lacking both Vhl and Hifla had a bone phenotype intermediate between those of the single mutants, suggesting overlapping functions of HIFs in bone. These studies suggest that activation of the HIF alpha pathway in developing bone increases bone modeling events through cell-nonautonomous mechanisms to coordinate the timing, direction, and degree of new blood vessel formation in bone. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Boston, MA 02215 USA. Univ Kentucky, Dept Med, Lexington, KY USA. Georgia Inst Technol, Woodruff Sch Mech Engn, Atlanta, GA USA. Boston Univ, Med Ctr, Dept Orthoped Surg, Boston, MA USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA USA. Univ Calif San Diego, Div Biol Sci, San Diego, CA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Vet Adm Med Ctr, Birmingham, AL USA. RP Clemens, TL (reprint author), Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. EM tclemens@uab.edu RI Haase, Volker Hans/A-6758-2013; OI Haase, Volker Hans/0000-0002-7051-8994; Johnson, Randall/0000-0002-4084-6639; /0000-0002-0477-1211 FU NCI NIH HHS [R01 CA100787]; NIAMS NIH HHS [R01 AR049410] NR 42 TC 307 Z9 336 U1 8 U2 40 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 JUN PY 2007 VL 117 IS 6 BP 1616 EP 1626 DI 10.1172/JC131581 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 175ZJ UT WOS:000247052200021 PM 17549257 ER PT J AU Bergmeier, W Goerge, T Wang, HW Crittenden, JR Baldwin, ACW Cifuni, SM Housman, DE Graybiel, AM Wagner, DD AF Bergmeier, Wolfgang Goerge, Tobias Wang, Hong-Wei Crittenden, Jill R. Baldwin, Andrew C. W. Cifuni, Stephen M. Housman, David E. Graybiel, Ann M. Wagner, Denisa D. TI Mice lacking the signaling molecule CaIDAG-GEFI represent a model for leukocyte adhesion deficiency type III SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GTP-BINDING PROTEIN; NEUTROPHIL EMIGRATION; P-SELECTIN; INTEGRIN ALPHA(IIB)BETA(3); GLANZMANN THROMBASTHENIA; PLATELET-AGGREGATION; THROMBUS FORMATION; BETA(2) INTEGRINS; NADPH OXIDASE; MURINE MODEL AB Single gene mutations in beta integrins can account for functional defects of individual cells of the hematopoietic system. In humans, mutations in beta(2) integrin lead to leukocyte adhesion deficiency (LAD) syndrome and mutations in beta(3) integrin cause the bleeding disorder Glanzmarm thrombasthenia. However, multiple defects in blood cells involving various beta integrins (beta(1), beta(2), and beta(3)) occur simultaneously in patients with the recently described LAD type III (LAD-III). Here we show that the product of a single gene, Ca2+ and diacylglycerol-regulated guanine nucleotide exchange factor 1 (CaIDAG-GEFI), controlled the activation of all 3 integrins in the hematopoietic system. Neutrophils from CalDAG-GEFI(-/-) mice exhibited strong defects in Rap1 and beta(1) and beta(2) integrin activation while maintaining normal calcium flux, degranulation, and ROS generation. Neutrophils from CalDAG-GEFI deficient mice failed to adhere firmly to stimulated venules and to migrate into sites of inflammation. Furthermore, CaIDAG-GEFI regulated the activation of beta(1) and beta(3) integrins in platelets, and CaIDAG-GEFI deficiency caused complete inhibition of arterial thrombus formation in mice. Thus, mice engineered to lack C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. MIT, Ctr Cancn Res, Cambridge, MA 02139 USA. RP Wagner, DD (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM bergmeier@cbrinstitute.org; wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [R37-HL41002, R37 HL041002]; NICHD NIH HHS [R01 HD028341, R01-HD28341]; NIMH NIH HHS [F32 MH065815, F32-MH065815] NR 53 TC 125 Z9 127 U1 0 U2 2 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 JUN PY 2007 VL 117 IS 6 BP 1699 EP 1707 DI 10.1172/JCI30575 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 175ZJ UT WOS:000247052200029 PM 17492052 ER PT J AU Song, YL Liu, CX Finegold, SM AF Song, Yuli Liu, Chengxu Finegold, Sydney M. TI Peptoniphilus gorbachii sp nov., Peptoniphilus olsenii sp nov., and Anaerococcus murdochii sp nov isolated from clinical specimens of human origin SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POSITIVE ANAEROBIC COCCI; GENUS PEPTOSTREPTOCOCCUS; PROPOSAL; IDENTIFICATION; MEMBERS; MAGNUS AB Three groups of previously unknown gram-positive, anaerobic, coccus-shaped bacteria were characterized using phenotypic and molecular taxonomic methods. Phenotypic and genotypic data demonstrate that these organisms are distinct, and each group represents a previously unknown subline within Clostridium cluster XIII. Two groups are most closely related to Peptoniphilus harei in the genus Peptoniphilus, and the other group is most closely related to Anaerococcus lactolyticus in the genus Anaerococcus. Based on the findings, three novel species, Peptoniphilus gorbachii sp. nov., Peptoniphilus olsenii sp. nov., and Anaerococcus murdochii sp. nov., are proposed. The type strains of Peptoniphilas gorbachii sp. nov., Peptoniphilus olsenii sp. nov., and Anaerococcus murdochii sp. nov. are WAL 10418(T) (= CCUG 53341(T) = ATCC BAA-1383(T)), WAL 12922(T) (= CCUG 53342(T) (=) ATCC BAA-1384(T)), and WAL 17230(T) (= CCUG 53340(T) = ATCC BAA-1385(T)), respectively. C1 W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA USA. RP Song, YL (reprint author), W Los Angeles Vet Affairs Med Ctr, Res Serv, Bldg 304,Rm E3-227,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yulis1@yahoo.com NR 20 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2007 VL 45 IS 6 BP 1746 EP 1752 DI 10.1128/JCM.00213-07 PG 7 WC Microbiology SC Microbiology GA 179JT UT WOS:000247286500012 PM 17428937 ER PT J AU Heist, RS Zhou, W Chirieac, LR Cogan-Drew, T Liu, G Su, L Neuberg, D Lynch, TJ Wain, JC Christiani, DC AF Heist, Rebecca Suk Zhou, Wei Chirieac, Lucian R. Cogan-Drew, Thea Liu, Geoffrey Su, Li Neuberg, Donna Lynch, Thomas J. Wain, John C. Christiani, David C. TI MDM2 polymorphism, survival, and histology in early-stage non-small-cell lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; MUTATIONAL HOTSPOTS; P53 PROTEIN; PROMOTER; PROGNOSIS; SUSCEPTIBILITY; AMPLIFICATION; EXPRESSION; PATHWAY; RISK AB Purpose MDM2 is a negative regulator of p53. The MDM2 309T/G polymorphism has been associated with differential MDM2 expression levels and inhibition of the p53 pathway. We hypothesized that the MDM2 GIG genotype may be associated with worse survival outcomes in lung cancer, especially in squamous cell cancers where p53 abnormalities are more common. Patients and Methods We evaluated the relationship between MDM2 polymorphism status and overall survival (OS) among patients with early-stage non-small-cell lung cancer (NSCLC) treated with surgical resection at Massachusetts General Hospital from 1992 to 2000. Kaplan-Meier methods and the log-rank test were used to compare survival by polymorphism status. Cox proportional hazards models were used to adjust for possible confounding variables. Results There were 383 patients in the analysis. In the early-stage population as a whole, the GIG genotype seemed to be associated with worse OS on adjusted analysis (adjusted hazard ratio = 1.57; 95% Cl, 1.03 to 2.40; P =.04). Among patients with squamous histology, OS was significantly worse among those with the GIG genotype (P =.0001 by log-rank test), with 5-year survival rates among the genotypes of 59% for T/T 53% for T/G, and 7% for G/G. Conclusion Our findings suggest that the GIG genotype of the MDM2 polymorphism is associated with worse OS among early-stage NSCLC patients, particularly those with squamous cell histology. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA074386, CA090578, CA092824] NR 27 TC 40 Z9 41 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2007 VL 25 IS 16 BP 2243 EP 2247 DI 10.1200/JCO.2006.08.8914 PG 5 WC Oncology SC Oncology GA 175JR UT WOS:000247010400017 PM 17538168 ER PT J AU Cappuzzo, F Ligorio, C Janne, PA Toschi, L Rossi, E Trisolini, R Paioli, D Holmes, AJ Magrini, E Finocchiaro, G Bartolini, S Cancellieri, A Ciardiello, F Patelli, M Crino, L Varella-Garcia, M AF Cappuzzo, Federico Ligorio, Claudia Jaenne, Pasi A. Toschi, Luca Rossi, Elisa Trisolini, Rocco Paioli, Daniela Holmes, Alison J. Magrini, Elisabetta Finocchiaro, Giovanna Bartolini, Stefania Cancellieri, Alessandra Ciardiello, Fortunato Patelli, Marco Crino, Lucio Varella-Garcia, Marileila TI Prospective study of gefitinib in epidermal growth factor receptor fluorescence in situ hybridization-positive/phospho-akt-positive or never smoker patients with advanced non-small-cell lung cancer: The ONCOBELL trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INHIBITOR ZD1839 IRESSA; HER2 KINASE DOMAIN; GENE COPY NUMBER; TYROSINE KINASE; SMOKING HISTORY; PHASE-II; PROLONGED SURVIVAL; CIGARETTE-SMOKING; KRAS MUTATIONS; EGFR MUTATIONS AB Purpose In non-small-cell lung cancer (NSCLC), clinical and biologic predictors for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor sensitivity have been identified in retrospective studies, and there is urgent need to validate these results in prospective trials. The ONCOBELL trial is a prospective phase II study evaluating gefitinib sensitivity in NSCLC patients who never smoked or have increased EGFR gene copy number or activation of the antiapoptotic protein Akt. Patients and Methods EGFR gene copy number was evaluated using fluorescence in situ hybridization (FISH), and presence of phospho-Akt was evaluated using immunohistochemistry. Additional tests included immunohistochemistry analysis of EGFR, FISH analysis of HER2, and mutation analysis of EGFR, HER2, and K-ras. Results From November 2004 to February 2006, 183 patients were screened, and 42 patients were enrolled onto the trial. We observed one complete and 19 partial responses, for an overall response rate (FIR) of 47.6% (95% Cl, 32.5% to 62.7%). Median duration of response was 6.1 months, median time to progression (TTP) was 6.4 months, 1-year survival rate was 64.3%, and median survival time was not reached. EGFR FISH-positive patients, compared with negative patients, had higher FIR (68.0% v 9.1 %, respectively; P <.001), longer TTP (7.6 v 2.7 months, respectively; P =.02), and a trend for longer survival (median survival not reached v 7.4 months, respectively; P =.3). Therapy was well tolerated, and there were no drug-related deaths. Median follow-up time was too short for significance tests of differences in survival outcomes. Conclusion Gefitinib is active and well tolerated in patients with trial characteristics, and EGFR FISH analysis is an accurate predictor for such therapy. C1 IRCCS, Ist Clin Humanitas, Dept Hematol Oncol, I-20089 Rozzano, Italy. Bellaria Maggiore Hosp, Bologna, Italy. CINECA Interuniv Consortium, Bologna, Italy. Univ Naples 2, Dept Med Oncol, Naples, Italy. Monteluce Policlin, Dept Med Oncol, Perugia, Italy. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Colorado, Ctr Canc, Dept Med Med Oncol, Aurora, CO USA. RP Cappuzzo, F (reprint author), IRCCS, Ist Clin Humanitas, Dept Hematol Oncol, Via Manzoni 56, I-20089 Rozzano, Italy. EM federico.cappuzzo@humanitas.it OI Ciardiello, Fortunato/0000-0002-3369-4841; Cappuzzo, Federico/0000-0002-6295-6767 FU NCI NIH HHS [1K12CA87723-01, 1R01CA114465-01] NR 50 TC 151 Z9 159 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2007 VL 25 IS 16 BP 2248 EP 2255 DI 10.1200/JCO.2006.09.4300 PG 8 WC Oncology SC Oncology GA 175JR UT WOS:000247010400018 PM 17538169 ER PT J AU Birrer, MJ Johnson, ME Hao, K Wong, KK Park, DC Bell, A Welch, WR Berkowitz, RS Mok, SC AF Birrer, Michael J. Johnson, Michael E. Hao, Ke Wong, Kwong-Kwok Park, Dong-Choon Bell, Aaron Welch, William R. Berkowitz, Ross S. Mok, Samuel C. TI Whole genome oligonucleotide-based array comparative genomic hybridization analysis identified fibroblast growth factor I as a prognostic marker for advanced-stage serous ovarian adenocarcinomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 01-05, 2006 CL Washington, DC SP Amer Assoc Canc Res ID COPY-NUMBER CHANGES; BREAST-CANCER; ANGIOGENESIS; DNA; MICROARRAY; TUMORS; CGH AB Purpose To identify markers that can predict overall survival in patients with high-grade advanced stage serous adenocarcinomas. Patients and Methods Oligonucleotide array comparative genomic hybridization (aCGH) was performed on 42 microdissected high-grade serous ovarian tumor samples. aCGH segments were obtained and a prediction Cox model was built and validated by the standard leave one out analysis. Both DNA and mRNA copy numbers of selected genes located on the candidate aCGH segments were determined by quantitative polymerase chain reaction (qPCR) and quantitative reverse transcriptase PCR (qRT-PCR) analyses. The gene that showed the highest correlation was further validated on an independent set of specimens and was selected for further functional studies. Results Two chromosomal regions, 4p16.3 and 5q31-5q35.3, exhibited the strongest correlation with overall survival (P <.01). From the 5q31 region, fibroblast growth factor 1 (FGF-1) was selected for further validation study. FGF-1 mRNA copy number was significantly correlated with DNA copy number and protein expression levels (P =.021 and <.001), and both FGF-1 mRNA and protein levels were significantly associated with overall survival (P =.018 and.042). This association was validated for protein expression on an independent set of 81 samples, significant to P =.006. Further studies showed significant correlation between FGF-1 protein expression and CD31 + staining in the tumor stroma (P =.024). Finally, both cancer cells and endothelial cells treated with exogenous FGF-1 showed a significant increase in cell motility and survival. Conclusion Amplification of FGF-1 at 5q31 in ovarian cancer tissues, leads to increased angiogenesis, and autocrine stimulation of cancer cells, which may result in poorer overall survival in patents with high-grade advanced stage serous ovarian cancer. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA 02115 USA. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Dana Farber Harvard Canc Ctr, Gillette Ctr Womens Canc, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Catholic Univ Korea, St Vincent Hosp, Dept Obstet & Gynecol, Suwon, South Korea. RP Mok, SC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Gynecol Oncol,Dept Obstet & Gynecol, BLI-447,221 Longwood Ave, Boston, MA 02115 USA. EM scmok@rics.bwh.harvard.edu FU Intramural NIH HHS; NCI NIH HHS [P50CA083639, P50CA105009, R33CA103595] NR 27 TC 74 Z9 76 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2007 VL 25 IS 16 BP 2281 EP 2287 DI 10.1200/JCO.2006.09.0795 PG 7 WC Oncology SC Oncology GA 175JR UT WOS:000247010400023 PM 17538174 ER PT J AU Pelloski, CE Ballman, KV Furth, AF Zhang, L Lin, E Sulman, EP Bhat, K McDonald, JM Yung, WKA Colman, H Woo, SY Heimberger, AB Suki, D Prados, MD Chang, SM Barker, FG Buckner, JC James, CD Aldape, K AF Pelloski, Christopher E. Ballman, Karla V. Furth, Alfied F. Zhang, Li Lin, E. Sulman, Erik P. Bhat, Krishna McDonald, J. Matthew Yung, W. K. Alfred Colman, Howard Woo, Shiao Y. Heimberger, Amy B. Suki, Dima Prados, Michael D. Chang, Susan M. Barker, Fred G., II Buckner, Jan C. James, C. David Aldape, Kenneth TI Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-GRADE GLIOMA; RECURSIVE PARTITIONING ANALYSIS; ACCELERATED RADIATION-THERAPY; ACTIVATED PROTEIN-KINASE; PHASE-I EVALUATION; PHOSPHATIDYLINOSITOL 3-KINASE; PREIRRADIATION CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; MULTIFORME; EGFRVIII AB Purpose The clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression in glioblastoma multiforme (GBM) and its relationship with other key molecular markers are not clear. We sought to evaluate the clinical significance of GBM subtypes as defined by EGFRvIII status. Patients and Methods The expression of EGFRvIII was assessed by immunohistochemistry in 649 patients with newly diagnosed GBM. These data were then examined in conjunction with the expression of phospho-intermediates (in a subset of these patients) of downstream AKT and Ras pathways and YKL-40 as well as with known clinical risk factors, including the Radiation Therapy Oncology Group's recursive partitioning analysis (RTOG-RPA) class. Results The RTOG-RPA class was highly predictive of survival in EGFRvIII-negative patients but much less predictive in EGFRvIII-positive patients. These findings were seen in both an initial test set (n = 268) and a larger validation set (n = 381). Similarly, activation of the AKT/MAPK pathways and YKL-40 positivity were predictive of poor outcome in EGFRvIII-negative patients but not in EGFRvIII-positive patients. Pair-wise combinations of markers identified EGFRvIII and YKL-40 as prognostically important. In particular, outcome in patients with EGFRvIII-negative/YKL-40-negative tumors was significantly better than the outcome in patients with the other three combinations of these two markers. Conclusion Established prognostic factors in GBM were not predictive of outcome in the EGFRvIII-positive subset, although this requires confirmation in independent data sets. GBMs negative for both EGFRvIII and YKL-40 show less aggressive behavior. C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. Mayo Clin, Div Biostat, Rochester, MN USA. Mayo Clin, Div Expt Pathol, Rochester, MN USA. Mayo Clin, Dept Med Oncol, Rochester, MN USA. Univ Calif San Francisco, Sch Med, Dept Neurosurg, San Francisco, CA USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Aldape, K (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Unit 85,1515 Holcombe Blvd, Houston, TX 77030 USA. EM kaldape@mdanderson.org RI James, Charles/E-2721-2012 OI James, Charles/0000-0002-1027-203X NR 44 TC 161 Z9 169 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2007 VL 25 IS 16 BP 2288 EP 2294 DI 10.1200/JCO.2006.08.0705 PG 7 WC Oncology SC Oncology GA 175JR UT WOS:000247010400024 PM 17538175 ER PT J AU Han, TH Harmatz, JS Greenblatt, DJ Martyn, JAJ AF Han, Taehyung Harmatz, Jerold S. Greenblatt, David J. Martyn, J. A. Jeevendra TI Fentanyl clearance and volume of distribution are increased in patients with major burns SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE pharmacokinetics; cardiac index; hepatic blood flow; opiates ID THERMAL-INJURY; CONTROLLED ANALGESIA; METABOLIC-RESPONSE; CARDIAC-OUTPUT; PHARMACOKINETICS; ALFENTANIL; PAIN; ITRACONAZOLE; DISPOSITION; DYSFUNCTION AB This study examined the pharmacokinetics of fentanyl in burned patients during the hyperdynamic phase. Twenty adults, aged 37 +/- 2 years (mean SE), with 49 +/- 3% total body surface area burn, were studied at 17 +/- 2 days after the injury and compared to demographically matched controls. After a 200-mu g IV bolus of fentanyl, blood samples (n = 20) were collected for 4.5 hours. Concentration-time curves were fitted to a 2-compartment model. Burned patients had a higher cardiac index. Median fentanyl clearance (CL, 21.0 vs 29.4 mL/kg/min), central comportment volume (V-1, 0.37 vs 0.61 L/kg), and total volume of distribution (V-area, 3.6 vs 5.8 L/kg) were higher in burned patients. Cardiac index was unrelated to CL. The increased V-1 and V-area are likely due to large intravenous fluid replacement and tissue edema. Higher CL and larger V-1 and V-area leading to a lower fentanyl plasma concentration may partially explain the increased opiate requirement previously observed after burn injury. C1 Univ Iowa Hosp & Clin, Dept Anesthesia, Carver Coll Med, Iowa City, IA 52242 USA. Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. RP Han, TH (reprint author), Univ Iowa Hosp & Clin, Dept Anesthesia, Carver Coll Med, 5936 JPP,200 Hawkins Dr, Iowa City, IA 52242 USA. EM anthony-han@uiowa.edu FU NCCIH NIH HHS [AT-01381]; NCRR NIH HHS [RR-00054]; NIA NIH HHS [AG-17780]; NIDA NIH HHS [DA-05258]; NIGMS NIH HHS [GM 31569, GM 55082, R01 GM055082] NR 39 TC 16 Z9 16 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUN PY 2007 VL 47 IS 6 BP 674 EP 680 DI 10.1177/0091270007299756 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 173RD UT WOS:000246889300001 PM 17428913 ER PT J AU Papakostas, GI Shelton, RC Smith, J Fava, M AF Papakostas, George I. Shelton, Richard C. Smith, Juliana Fava, Maurizio TI Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: A meta-analysis SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; OLANZAPINE/FLUOXETINE COMBINATION; RISPERIDONE AUGMENTATION; ARIPIPRAZOLE AUGMENTATION; OPEN-LABEL; OLANZAPINE; FLUOXETINE; SSRI; ZIPRASIDONE; QUETIAPINE AB Objective: To examine the efficacy and overall tolerability of augmentation of standard antidepressants with atypical antipsychotic agents for treatment-resistant major depressive disorder. Data Sources: MEDLINE/PubMed, EMBASE, the Cochrane database, and program syllabi from major psychiatric meetings held since 2000 as well as a number of online clinical trial results registries were searched. Makers of atypical antipsychotic agents who do not maintain an online clinical study results registry were contacted directly. Study Selection: Double-blind, randomized, placebo-controlled clinical trials assessing adjunctive treatment of standard antidepressants with an atypical antipsychotic agent for treatment-resistant major depressive disorder were identified. Data Extraction: Data were extracted with the use of a pre-coded form. Data Synthesis: Data from 10 clinical trial reports involving a total of 1500 outpatients with treatment-resistant major depressive disorder were identified and combined using a random-effects model. Patients randomized to adjunctive treatment with an atypical antipsychotic agent were more likely to experience remission (risk ratio [RR] = 1.75, p < .0001) or clinical response (RR = 1.35, p = .001) than patients who received adjunctive placebo. Pooled remission and response rates for the 2 treatment groups were 47.4% vs. 22.3% and 57.2% vs. 35.4%, respectively. Although there was no difference in overall discontinuation rates (p = .929) or the rate of discontinuation due to inefficacy (p = .133) between the 2 treatment groups, the rate of discontinuation due to adverse events was lower among placebo-treated patients (RR = 3.38, p < .0001). Conclusions: These results support the utility of augmenting standard antidepressants with atypical antipsychotic agents for treatment-resistant major depressive disorder. An obvious limitation of this work is the absence of data focusing on the use of aripiprazole and ziprasidone. Future short- as well as long-term studies comparing the efficacy, safety, and tolerability of this versus other adjunctive strategies are warranted. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. RP Papakostas, GI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629, K24 MH01741] NR 45 TC 133 Z9 139 U1 2 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 JUN PY 2007 VL 68 IS 6 BP 826 EP 831 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 183FT UT WOS:000247558800002 PM 17592905 ER PT J AU Grand, RBG Hwang, S Han, J George, T Brody, AL AF Grand, Risa B. Gershon Hwang, Sun Han, Juliette George, Tony Brody, Arthur L. TI Short-term naturalistic treatment outcomes in cigarette smokers with substance abuse and/or mental illness SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the Society-for-Research-on-Nicotine-and-Tobacco CY FEB 15-18, 2006 CL Orlando, FL SP Soc Res Nicotine & Tobacco ID METHADONE-MAINTENANCE TREATMENT; POSTTRAUMATIC-STRESS-DISORDER; BUPROPION SUSTAINED-RELEASE; PLACEBO-CONTROLLED TRIAL; NICOTINE PATCH THERAPY; OF-VETERANS-AFFAIRS; SMOKING-CESSATION; MAJOR DEPRESSION; UNITED-STATES; EPIDEMIOLOGIC SURVEY AB Objective: The majority of cigarette smokers have a lifetime diagnosis of substance abuse and/or mental illness, and treatment outcomes for smokers with these comorbidities are generally reported to be worse than for smokers without comorbidities. We sought to examine the effect of specific substance abuse/mental illness diagnoses compared to one another on treatment outcomes. Method: A retrospective chart review of naturalistic treatment for nicotine dependence was performed on male smokers (N = 231) who enrolled in the Greater Los Angeles Veterans Affairs Mental Health Clinic Smoking Cessation Program (Los Angeles, Calif.) over a 1.5-year period (January 2004 to June 2005). Subjects in this program, who were diagnosed with nicotine dependence on the basis of a DSM-lV-based interview and a Fagerstrom Test for Nicotine Dependence score of ! 3, underwent comprehensive treatment for nicotine dependence (including, but not limited to, group psychotherapy, nicotine replacement therapy, and bupropion hydrochloride). Quitting smoking was defined as a report of at least I week of abstinence and an exhaled carbon monoxide less than or equal to 8 parts per million at the final clinic visit. Results: Of the total group, 36.4% (84/231) quit smoking at the end of treatment. Quit rates were affected by the presence of specific diagnoses, with smokers with a history of alcohol abuse/dependence or schizophrenia/schizoaffective disorder having poorer response rates than smokers without such diagnoses. Other substance abuse and mental illness diagnoses did not affect quit rates. Conclusion: Lower quit rates among patients with alcohol abuse/dependence or schizophrenia/schizoaffective disorder may be due to the severity of these conditions and suggest that specialized treatment is needed for these populations of smokers. Smokers with most comorbid diagnoses are successfully treated with standard treatment methods. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Yale Univ, Sch Med, New Haven, CT USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu NR 73 TC 20 Z9 21 U1 1 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 JUN PY 2007 VL 68 IS 6 BP 892 EP 898 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 183FT UT WOS:000247558800011 ER PT J AU Joffe, H Soares, CN Petrillo, LF Viguera, AC Somley, BL Koch, JK Cohen, LS AF Joffe, Hadine Soares, Claudio N. Petrillo, Laura F. Viguera, Adele C. Somley, Brittny L. Koch, Jennifer K. Cohen, Lee S. TI Treatment of depression and menopause-related symptoms with the serotonin-norepinephrine reuptake inhibitor duloxetine SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 159th Annual Meeting of the American-Psychiatric-Association CY MAY 20-25, 2006 CL Toronto, CANADA SP Amer Psychiat Assoc ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; HOT FLASHES; BREAST-CANCER; DOUBLE-BLIND; PSYCHOMETRIC PROPERTIES; REPLACEMENT THERAPY; VASOMOTOR SYMPTOMS; HORMONE-THERAPY; SLEEP AB Background: Postmenopausal women with depression frequently have co-occurring symptoms of hot flashes (vasomotor symptoms), sleep disturbance, anxiety, and pain. Treatment strategies that target all of these symptoms together have not been investigated to date. Method: Study participants were postmenopausal women, 40 to 60 years old, with major depressive disorder (DSM-IV criteria) and vasomotor symptoms. The study design included a 2-week, single-blind placebo run-in phase followed by an 8-week open-label flexible-dosing (60-120 mg per day) study of duloxetine for women who did not respond to placebo. The primary outcome measure was change in Montgomery-Asberg Depression Rating Scale (MADRS) score during 8 weeks of duloxetine therapy. Secondary outcome measures included changes in vasomotor symptoms, sleep quality, anxiety, and pain. Analyses were conducted using non-parametric methods. Patients were enrolled in the study from May 31, 2005, through May 22, 2006. Results: Of 30 women eligible to participate in this study, 20 initiated treatment with open-label duloxetine. Fourteen (70.0%) of these women completed the study. There was a statistically significant decrease in MADRS scores after 8 weeks of treatment (p < .001), with scores declining from 19.0 (interquartile range [IQR] = 15.0-21.0) to 5.5 (IQR = 3.0-9.0). There was also a statistically significant improvement in vasomotor symptoms (p = .003), anxiety (p = .002), sleep quality (p < .001), and pain (p < .05). Conclusions: Postmenopausal women with depression and vasomotor symptoms had significant improvement in depression, vasomotor symptoms, sleep, anxiety, and pain after 8 weeks of open-label duloxetine therapy. Given the common co-occurrence of these symptoms in postmenopausal women, duloxetine may offer important therapeutic benefits for postmenopausal women who have depression and menopause-related symptoms. C1 Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. RP Joffe, H (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Program, 185 Cambridge St,suite 2000, Boston, MA 02114 USA. EM hjoffe@partners.org NR 45 TC 48 Z9 51 U1 2 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 JUN PY 2007 VL 68 IS 6 BP 943 EP 950 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 183FT UT WOS:000247558800019 PM 17592922 ER PT J AU Miller, KK Wexler, TL Zha, AM Lawson, EA Meenaghan, EM Misra, M Binstock, AB Herzog, DB Klibanski, A AF Miller, Karen K. Wexler, Tamara L. Zha, Alicia M. Lawson, Elizabeth A. Meenaghan, Erinne M. Misra, Madhusmita Binstock, Anna B. Herzog, David B. Klibanski, Anne TI Androgen deficiency: Association with increased anxiety and depression symptom severity in anorexia nervosa SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID EATING-DISORDERS; DOUBLE-BLIND; DEHYDROEPIANDROSTERONE REPLACEMENT; PSYCHIATRIC COMORBIDITY; MALE RATS; TESTOSTERONE; WOMEN; BEHAVIOR; TRIAL; FEAR AB Objective: Anorexia nervosa is associated with a high prevalence of psychiatric comorbidities, including anxiety and depression, and with endocrine dysfunction, including relative androgen deficiency compared with healthy young women. Because androgens are known to affect mood and behavior, we hypothesized that low endogenous androgen production in anorexia nervosa would predict anxiety and depression severity. Method: Serum androgen levels and severity of depression (Hamilton Rating Scale for Depression) and anxiety (Hamilton Rating Scale for Anxiety) were measured in 43 community-dwelling women with DSM-IV-defined anorexia nervosa from May 2004 to July 2006. Results: Strong inverse associations were observed between both total and free testosterone and anxiety and depression severity, independent of weight. Free testosterone was also inversely associated with 4 eating-disordered thinking and behavior subscales of the Eating Disorder Inventory 2 (EDI-2). Mean free testosterone blood levels were lower in women with clinically significant anxiety and in women with clinically significant depression, compared with those without. In stepwise regression models, free testosterone was an important predictor of anxiety and depression severity. EDI-2 ineffectiveness, perfectionism, interpersonal distress, and social insecurity scores were also inversely associated with androgen levels, independent of weight. Conclusions: Our data suggest that low androgen levels may contribute to anxiety, depression, and eating-disordered thinking and behavior in women with anorexia nervosa and form the basis for future studies to investigate the effectiveness of androgen replacement therapy. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harris Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@Partners.org FU NCRR NIH HHS [M01 RR01066]; NIDDK NIH HHS [R01-DK52625] NR 28 TC 22 Z9 23 U1 1 U2 4 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 JUN PY 2007 VL 68 IS 6 BP 959 EP 965 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 183FT UT WOS:000247558800021 PM 17592924 ER PT J AU Cully, JA Graham, DP Stanley, MA Kunik, ME AF Cully, Jeffrey A. Graham, David P. Stanley, Melinda A. Kunik, Mark E. TI Depressed and anxious COPD patients: Predictors of psychotherapy engagement from a clinical trial SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE engagement in mental health treatment; anxiety; depression; chronic obstructive pulmonary disease ID PRIMARY-CARE PATIENTS; QUALITY-OF-LIFE; MAJOR DEPRESSION; ANXIETY; INTERVENTION; ATTITUDES; SYMPTOMS; DISEASE AB This study examined patient-level factors associated with engagement in mental health treatment in a sample of medically ill patients with clinically significant symptoms of depression and/or anxiety. A total of 248 patients was enlisted from a randomized controlled trial of cognitive-behavioral therapy for depression and anxiety in patients with chronic obstructive pulmonary disease (COPD). Logistic regression analysis was used to predict mental health engagement, defined as attending at least one intervention session. Results indicated that patient-perceived mastery over COPD was negatively related to mental health engagement. Further, mastery was the only significant predictor of mental health engagement after controlling for patient demographic characteristics, severity of COPD, depression, and anxiety. To improve engagement for medically ill patients with comorbid mental health difficulties, clinicians should explore patients' attitudes about their mental health within the context of their perceived ability to cope with their medical disease. C1 Michael E Debakey Vet Affairs Med Ctr, Vet Affairs HSR&D Ctr Excellence, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA. RP Cully, JA (reprint author), Michael E Debakey Vet Affairs Med Ctr, Vet Affairs HSR&D Ctr Excellence, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe 152, Houston, TX 77030 USA. EM jcully@bcm.edu RI Graham, David /J-1158-2014 NR 16 TC 4 Z9 4 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD JUN PY 2007 VL 14 IS 2 BP 160 EP 164 DI 10.1007/s10880-007-9060-0 PG 5 WC Psychology, Clinical SC Psychology GA 201EO UT WOS:000248814500009 ER PT J AU Bromley, B Shipp, TD Benacerraf, B AF Bromley, Bryann Shipp, Thomas D. Benacerraf, Beryl TI Assessment of the third-trimester fetus using 3-dimensional volumes: A pilot study SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Article DE third-trimester ultrasound; 3D volume imaging ID INDIVIDUALIZED GROWTH ASSESSMENT; 4-DIMENSIONAL ULTRASOUND; FETAL; SONOGRAPHY; ULTRASONOGRAPHY AB Purpose. To examine whether the third-trimester fetus can be assessed sonographically using 3-dimensional (3D) volume data sets. Methods. Twenty-seven consecutive third-trimester fetuses were evaluated. Fetuses were scanned using 2-dimensional (2D) imaging followed by 5 3D volume acquisitions. The initial scan was interpreted and reported based on the 2D images. The 3D volume data sets were independently reviewed offline several weeks later by 2 sonologists. Parameters evaluated included fetal presentation, placental location, amniotic fluid volume, fetal biometry including a calculation of estimated fetal weight, and major fetal anatomic structures. The result of the interpretation via 3D reconstruction of the volume from each of the 2 sonologists was compared with the original 2D sonography report. Results. Fetal presentation, amniotic fluid volume, and placental location with respect to the cervix were correctly identified 100% of the time by each sonologist. The estimated fetal weight was within 10% of the 2D estimate 89% (95% CI, 0.71-0.98) of the time for sonologist A and 96% (95% CI, 0.81-0-99) of the time for sonologist B. The majority of major anatomic landmarks were adequately seen by both sonologists. Conclusion. Offline review of 3D volume data sets is a reliable method for determining fetal presentation, amniotic fluid volume, placental location, and estimating fetal weight in the third trimester. (c) 2007 Wiley Periodicals, Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol & Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol & Obstet & Gynecol, Boston, MA 02115 USA. RP Bromley, B (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol & Obstet & Gynecol, Boston, MA 02115 USA. NR 22 TC 10 Z9 10 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD JUN PY 2007 VL 35 IS 5 BP 231 EP 237 DI 10.1002/jcu.20379 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 175EX UT WOS:000246996900001 PM 17444536 ER PT J AU Street, AE Gradus, JL Stafford, J Kelly, K AF Street, Amy E. Gradus, Jaimie L. Stafford, Jane Kelly, Kacie TI Gender differences in experiences of sexual harassment: Data from a male-dominated environment SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE sexual harassment; gender differences; mental health ID MILITARY PERSONNEL; SEQ-DOD; MEN; WOMEN; QUESTIONNAIRE; PREVALENCE; PREDICTORS; DISORDER; STUDENTS; ASSAULT AB The goal of this investigation was to examine gender differences in experiences of sexual harassment during military service and the negative mental health symptoms associated with these experiences. Female (n = 2,319) and male (n = 1,627) former reservists were surveyed about sexual harassment during their military service and current mental health symptoms. As expected, women reported a higher frequency of sexual harassment. Further, women had increased odds of experiencing all subtypes of sexual harassment. Being female conferred the greatest risk for experiencing the most serious forms of harassment. For both men and women, sexual harassment was associated with more negative current mental health. However, at higher levels of harassment, associations with some negative mental health symptoms were stronger for men than women. Although preliminary, the results of this investigation suggest that although women are harassed more frequently than men, clinicians must increase their awareness of the potential for sexual harassment among men in order to provide the best possible care to all victims of harassment. C1 Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD 116B 3, Womens Hlth Sci Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. RP Street, AE (reprint author), Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD 116B 3, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. EM amy.street@va.gov NR 49 TC 70 Z9 72 U1 2 U2 7 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD JUN PY 2007 VL 75 IS 3 BP 464 EP 474 DI 10.1037/0022-006X.75.3.464 PG 11 WC Psychology, Clinical SC Psychology GA 177SC UT WOS:000247171800012 PM 17563163 ER PT J AU Taylor, JG Baker, SB AF Taylor, John G. Baker, Stanley B. TI Psychosocial and moral development of PTSD-diagnosed combat veterans SO JOURNAL OF COUNSELING AND DEVELOPMENT LA English DT Article AB Two related studies were conducted in order to investigate whether psychosocial and moral development appeared to have been disrupted and arrested in veterans diagnosed as having posttraumatic stress disorder (PTSD). Study 1 was devoted to developing a measure of late adolescence, early adulthood, and adulthood stages of psychosocial development. In Study 2, a sample of 32 PTSD-diagnosed and 32 PTSD-free veterans participated. The PTSD-diagnosed participants presented evidence of arrested psychosocial and moral development. C1 US Dept Vet Affairs, Vocat Rehabil & Employment, Jacksonville, NC 28540 USA. N Carolina State Univ, Counselor Educ Program, Raleigh, NC 27695 USA. RP Taylor, JG (reprint author), US Dept Vet Affairs, Vocat Rehabil & Employment, Box 4360 MCAS, Jacksonville, NC 28540 USA. EM ADJJTAYL2@vba.va.gov NR 26 TC 2 Z9 2 U1 1 U2 1 PU AMER COUNSELING ASSOC PI ALEXANDRIA PA 5999 STEVENSON AVE, ALEXANDRIA, VA 22304-3300 USA SN 0748-9633 J9 J COUNS DEV JI J. Couns. Dev. PD SUM PY 2007 VL 85 IS 3 BP 364 EP 369 PG 6 WC Psychology, Applied SC Psychology GA 181RF UT WOS:000247453100012 ER PT J AU Hirshfeld-Becker, DR Biederman, J Henin, A Faraone, SV Davis, S Harrington, K Rosenbaum, JF AF Hirshfeld-Becker, Dina R. Biederman, Joseph Henin, Aude Faraone, Stephen V. Davis, Stephanie Harrington, Kara Rosenbaum, Jerrold F. TI Behavioral inhibition in preschool children at risk is a specific predictor of middle childhood social anxiety: A five-year follow-up SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE behavioral inhibition; social anxiety; high risk; childhood anxiety ID ATTENTION-DEFICIT HYPERACTIVITY; NATIONAL-COMORBIDITY-SURVEY; PANIC DISORDER; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; YOUNG-CHILDREN; EARLY INTERVENTION; PARENTS; PHOBIA; ASSOCIATION AB Objective: Behavioral inhibition (BI) to the unfamiliar represents the temperamental tendency to exhibit fearfulness, reticence, or restraint when faced with unfamiliar people or situations. it has been hypothesized to be a risk factor for anxiety disorders. in this prospective longitudinal study, we compared the psychiatric outcomes in middle childhood of children evaluated at preschool age for BI. Method: The baseline sample consisted of 284 children ages 21 months to 6 years, including offspring at risk for anxiety (children of parents with panic disorder and/or major depression) and comparison offspring of parents without mood or major anxiety disorders. They had been assessed for BI using age-specific laboratory protocols. We reassessed 215 of the children (76.5%) at 5-year follow-up at a mean age of 9.6 years using structured diagnostic interviews. Results: Ell specifically predicted onset of social anxiety. The rate of lifetime social anxiety (DSM-IV social phobia or DSM-III-R avoidant disorder) was 28% versus 14% (odds ratio [OR] = 2.37; 95% confidence interval [CI]: 1.10 -5.10) in inhibited versus noninhibited children. BI significantly predicted new onset of social phobia among children unaffected at baseline (22.2% vs 8.0% in inhibited versus noninhibited children (OR = 3.15, 95% CI: 1.16-8.57). No other anxiety disorders were associated with Bl. Conclusion: BI appears to be a temperamental antecedent to subsequent social anxiety in middle childhood. Children presenting with BI should be monitored for symptoms of social anxiety and may be good candidates for preventive cognitive behavioral strategies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM dhirshfeld@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH047077-13] NR 66 TC 127 Z9 127 U1 7 U2 35 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 2007 VL 28 IS 3 BP 225 EP 233 DI 10.1097/01.DBP.0000268559.34463.d0 PG 9 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 178LD UT WOS:000247221300009 PM 17565290 ER PT J AU Jellinek, MS Hirst, J Stein, MT AF Jellinek, Michael S. Hirst, Jeremy Stein, Martin T. TI Giving bad news: A 13-year old with acute psychotic symptoms and catatonia SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Univ Calif San Diego, Rady Childrens Hosp, San Diego, CA USA. RP Jellinek, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 2007 VL 28 IS 3 BP 241 EP 244 DI 10.1097/DBP.0b013e3180674e61 PG 4 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 178LD UT WOS:000247221300012 PM 17565293 ER PT J AU Kougias, P El Sayed, HF Zhou, W Lin, PH AF Kougias, Panagiotis El Sayed, Hosam F. Zhou, Wei Lin, Peter H. TI Management of chronic mesenteric ischemia. The role of endovascular therapy SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Article DE mesenteric ischemia; endovascular therapy; surgical intervention; review ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; DRUG-ELUTING STENTS; INTESTINAL ISCHEMIA; OCCLUSIVE DISEASE; SURGICAL-TREATMENT; VISCERAL ISCHEMIA; ARTERY BYPASS; LATE OUTCOMES; FOLLOW-UP; REVASCULARIZATION AB Chronic mesenteric ischemia is an uncommon disorder manifested most commonly as abdominal pain. Surgical revascularization has traditionally been the treatment of choice. Endovascular management of this entity was originally attempted as an alternative for high-risk patients. Improvements in stent technology, refinement in technique, and increased efficiency of antiplatelet regimens have, over time, increased the popularity of this minimally invasive approach. We present a review of the available series on endovascular treatment of chronic mesenteric ischemia, with emphasis on short- and long-term outcome and morbidity and mortality results. Principles of operative technique and controversial issues and topics of interest are also discussed. C1 Baylor Coll Med, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston, TX USA. RP Kougias, P (reprint author), Houston VAMC, Michael E DeBakey Dept Surg, 2002 Holcombe Blvd 112, Houston, TX 77030 USA. EM pkougias@bcm.tmc.edu NR 48 TC 22 Z9 24 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD JUN PY 2007 VL 14 IS 3 BP 395 EP 405 DI 10.1583/07-2102.1 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 188KV UT WOS:000247919700018 PM 17723025 ER PT J AU Pirraglia, PA Murthy, V Weilburg, JB AF Pirraglia, Paul A. Murthy, Vyshali Weilburg, Jeffrey B. TI Primary care doctor attributions for why patients did not receive adequate antidepressant treatment SO JOURNAL OF EVALUATION IN CLINICAL PRACTICE LA English DT Article ID DEPRESSION C1 Providence VA Med Ctr, Hlth Serv Res & Dev Program, Integrate Psychosocial & Hlth Serv Chron Dis & Di, Providence, RI 02908 USA. Brown Univ, Providence, RI 02912 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Pirraglia, PA (reprint author), Providence VA Med Ctr, Hlth Serv Res & Dev Program, Integrate Psychosocial & Hlth Serv Chron Dis & Di, 830 Chalkstone Ave,Bldg T32, Providence, RI 02908 USA. EM paul.pirraglia@med.va.gov NR 9 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1356-1294 J9 J EVAL CLIN PRACT JI J. Eval. Clin. Pract. PD JUN PY 2007 VL 13 IS 3 BP 473 EP 475 DI 10.1111/j.1365-2753.2006.00788.x PG 3 WC Health Care Sciences & Services; Medical Informatics; Medicine, General & Internal SC Health Care Sciences & Services; Medical Informatics; General & Internal Medicine GA 169WD UT WOS:000246621900026 PM 17518819 ER PT J AU Taft, CT Street, AE Marshall, AD Dowdall, DJ Riggs, DS AF Taft, Casey T. Street, Amy E. Marshall, Amy D. Dowdall, Deborah J. Riggs, David S. TI Posttraumatic stress disorder, anger, and partner abuse among Vietnam combat veterans SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE posttraumatic stress disorder; anger; partner abuse; domestic violence; psychological aggression ID ADMINISTERED PTSD SCALE; BECK ANXIETY INVENTORY; MARITALLY VIOLENT; HOSTILITY; DEFICITS; VICTIMS; SAMPLE; DUTY; MEN AB The authors examined interrelationships among posttraumatic stress disorder (PTSD) symptomatology, anger, and partner abuse perpetration among a sample of 60 combat veterans. Compared with PTSD-negative participants, PTSD-positive participants reported higher state anger across time and neutral and trauma prime conditions and higher anger reactivity during the trauma prime condition. PTSD-positive participants also exhibited more anger reactivity during the trauma prime than during the neutral condition. The same pattern of results was not found for anxiety reactivity during trauma memory activation. PTSD symptoms were associated with physical assault and psychological aggression perpetration, and trait anger mediated these relationships. Findings indicate a heightened anger response among PTSD-positive veterans and suggest the salience of dispositional components of anger in abuse perpetration in this population. C1 Vet Affairs Boston Healthcare Syst, Behav Sci Div, Natl Ctr Posttraumat Stress Disorders, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Vet Affairs Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr Posttraumat Stress Disorders, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Univ Penn, Ctr Treatment & Study Anxiety, Philadelphia, PA 19104 USA. RP Taft, CT (reprint author), Vet Affairs Boston Healthcare Syst, Behav Sci Div, Natl Ctr Posttraumat Stress Disorders, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov NR 35 TC 89 Z9 90 U1 5 U2 11 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD JUN PY 2007 VL 21 IS 2 BP 270 EP 277 DI 10.1037/0893-3200.21.2.270 PG 8 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 186FG UT WOS:000247763900014 PM 17605549 ER PT J AU Fernandez-del Castillo, C AF Fernandez-del Castillo, Carlos TI "How I do it" session of the Pancreas Club SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Gen Surg, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Div Gen Surg, 15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD JUN PY 2007 VL 11 IS 6 BP 725 EP 725 DI 10.1007/s11605-007-0189-9 PG 1 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 178TE UT WOS:000247242200006 ER PT J AU Campbell, DG Felker, BL Liu, CF Yano, EM Kirchner, JE Chan, D Rubenstein, LV Chaney, EF AF Campbell, Duncan G. Felker, Bradford L. Liu, Chuan-Fen Yano, Elizabeth M. Kirchner, JoAnn E. Chan, Domin Rubenstein, Lisa V. Chaney, Edmund F. TI Prevalence of depression-PTSD comorbidity: Implications for clinical practice guidelines and primary care-based interventions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT National Annual Meeting of the US Department of Veterans Affairs Health Services Research and Development Service CY FEB, 2005 CL Baltimore, MD DE depression; PTSD; primary care; clinical practice guidelines ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; LATE-LIFE DEPRESSION; MAJOR DEPRESSION; SUICIDAL-BEHAVIOR; FUNCTIONAL STATUS; VETERANS HEALTH; SOCIAL SUPPORT; COMMUNITY; ASSOCIATION AB BACKGROUND: Compared to those with depression alone, depressed patients with posttraumatic stress disorder ( PTSD) experience more severe psychiatric symptomatology and factors that complicate treatment. OBJECTIVE: To estimate PTSD prevalence among depressed military veteran primary care patients and compare demographic/illness characteristics of PTSD screen-positive depressed patients (MDD-PTSD+) to those with depression alone (MDD). DESIGN: Cross-sectional comparison of MDD patients versus MDD-PTSD+ patients. PARTICIPANTS: Six hundred seventy-seven randomly sampled depressed patients with at least 1 primary care visit in the previous 12 months. Participants composed the baseline sample of a group randomized trial of collaborative care for depression in 10 VA primary care practices in 5 states. MEASUREMENTS: The Patient Health Questionnaire-9 assessed MDD. Probable PTSD was defined as a Primary Care PTSD Screen >= 3. Regression-based techniques compared MDD and MDD-PTSD+ patients on demographic/illness characteristics. RESULTS: Thirty-six percent of depressed patients screened positive for PTSD. Adjusting for sociodemographic differences and physical illness comorbidity, MDD-PTSD+ patients reported more severe depression (P <. 001), lower social support (P <. 001), more frequent outpatient health care visits (P <. 001), and were more likely to report suicidal ideation (P <. 001) than MDD patients. No differences were observed in alcohol consumption, self-reported general health, and physical illness comorbidity. CONCLUSIONS: PTSD is more common among depressed primary care patients than previously thought. Comorbid PTSD among depressed patients is associated with increased illness burden, poorer prognosis, and delayed response to depression treatment. Providers should consider recommending psychotherapeutic interventions for depressed patients with PTSD. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Dept Vet Affairs, Seattle, WA USA. Univ Montana, Dept Psychol, Missoula, MT 59812 USA. VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Dept Vet Affairs, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. VA Greater Los Angeles Healthcare Syst, Dept Vet Affairs, Hlth Serv Res & Dev Ctr Excellence, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Cent Arkansas Vet Healthcare Syst, Dept Vet Affairs, Hlth Serv Res & Dev, N Little Rock, AR USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RAND Corp, Hlth Program, Santa Monica, CA 90406 USA. RP Campbell, DG (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Dept Vet Affairs, Seattle, WA USA. EM Duncan.Campbell@umontana.edu NR 58 TC 134 Z9 134 U1 3 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2007 VL 22 IS 6 BP 711 EP 718 DI 10.1007/s11606-006-0101-4 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 169AA UT WOS:000246563900001 PM 17503104 ER PT J AU Crothers, K Goulet, JL Rodriguez-Barradas, MC Gibert, CL Butt, AA Braithwaite, RS Peck, R Justice, AC AF Crothers, Kristina Goulet, Joseph L. Rodriguez-Barradas, Maria C. Gibert, Cynthia L. Butt, Adeel A. Braithwaite, R. Scott Peck, Robin Justice, Amy C. TI Decreased awareness of current smoking among health care providers of HIV-positive compared to HIV-negative veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE tobacco; detection of smoking; HIV; smoking cessation ID HUMAN-IMMUNODEFICIENCY-VIRUS; CIGARETTE-SMOKING; ANTIRETROVIRAL THERAPY; BACTERIAL PNEUMONIA; INFECTED PERSONS; RANDOMIZED-TRIAL; MORTALITY-RATES; TOBACCO USE; DISEASE; DEATH AB BACKGROUND: Cigarette smoking is an important risk factor for morbidity and mortality in HIV-positive patients on combination antiretroviral therapy. OBJECTIVE: To determine whether awareness of smoking differs between HIV and non-HIV providers, and to identify factors associated with failure to recognize current smoking. DESIGN: Observational study. PARTICIPANTS: 801 HIV-positive and 602 HIV-negative patients, 72 HIV and 71 non-HIV providers enrolled in the Veterans Aging Cohort 5 Site Study. MEASUREMENTS: Data sources included patient and provider questionnaires; electronic medical records; and the national administrative VA database. We calculated sensitivity, specificity, and measures of agreement between patient-and provider-reported smoking, and examined factors associated with failure to recognize current smoking using logistic regression. RESULTS: Whereas most providers were correct when they identified a patient as a current smoker (specificity >= 90%), HIV providers missed current smoking more often (sensitivity 65% for HIV vs. 82% for non-HIV). Kappa scores for current smoking were significantly lower for HIV compared to non- HIV providers (0.55 vs. 0.75, p <.001). In models adjusted for age, gender, race, and other differences, patient HIV status and provider specialty in infectious diseases were independent predictors of a provider's failure to recognize current smoking. Comorbid illnesses, cough/dyspnea, degree of immune competence and HIV viral suppression did not impact recognition of current smoking. Only 39% of HIV providers reported confidence in their ability to influence smoking cessation compared to 62% of non-HIV providers (p=. 049). CONCLUSIONS: Interventions to increase HIV provider awareness of current smoking and skills to influence smoking cessation are needed. Efforts should also target patient populations with smoking-related comorbid diseases who would especially benefit from smoking cessation. C1 Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Michael A DeBakey VA Med Ctr, Med Serv, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. George Washington Univ, Washington, DC 20052 USA. VA Med Ctr, Med Serv, Washington, DC USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Dept Internal Med, Pittsburgh, PA USA. RP Justice, AC (reprint author), Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. EM amy.justice2@va.gov OI Goulet, Joseph/0000-0002-0842-804X; Crothers, Kristina/0000-0001-9702-0371 FU NCRR NIH HHS [K12 RR0117594-01]; NIAAA NIH HHS [3U01 AA 13566, U01 AA013566]; NIDA NIH HHS [K23 DA016175, K23 DA016175-01A1]; PHS HHS [K23 G00826] NR 31 TC 31 Z9 31 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2007 VL 22 IS 6 BP 749 EP 754 DI 10.1007/s11606-007-0158-8 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 169AA UT WOS:000246563900006 PM 17503106 ER PT J AU Kressin, NR Wang, F Long, J Bokhour, BG Orner, MB Rothendler, J Clark, C Reddy, S Kozak, W Kroupa, LP Berlowitz, DR AF Kressin, Nancy R. Wang, Fei Long, Judith Bokhour, Barbara G. Orner, Michelle B. Rothendler, James Clark, Christine Reddy, Surekha Kozak, Waldemar Kroupa, Laura P. Berlowitz, Dan R. TI Hypertensive patients' race, health beliefs, process of care, and medication adherence SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE physician-patient relations; patient compliance; attitude to health ID ANTIHYPERTENSIVE THERAPY; RACIAL-DIFFERENCES; VALIDATION; DISPARITIES; AWARENESS; MORTALITY; GENDER AB BACKGROUND: African Americans have higher rates of hypertension and worse blood pressure (BP) control than Whites, and poorer medication adherence may contribute to this phenomenon. We explored associations among patients' race, self-reported experiences with clinicians, attitudes and beliefs about hypertension, and ultimately, medication adherence, among a sample with no racial disparities in BP control, to determine what lessons we could learn from patients and providers in this setting. METHODS: We recruited 793 White and African-American (58%) patients previously diagnosed with hypertension from 3 VA medical centers to participate in survey assessments of each of the above dimensions, subsequent to a primary care clinic visit. RESULTS: African-American patients' providers were significantly more active in advising and counseling about hypertension care and medication adherence. African-American patients indicated greater knowledge or heightened awareness of the importance of controlling their BP, but there were no race differences on a summary adherence measure. In multivariate models modeling medication adherence, race was not significant, but having been told to split one's pills, believing one's BP continues to be high, and having one's provider discuss things to do to make it easier to take BP medications were each significantly associated with worse adherence, whereas having more confidence in one's ability to take BP medications as prescribed was associated with better adherence (all p's <=. 02). CONCLUSION: When both physicians and patients take BP management seriously, disparities in BP adherence and control may be reduced. C1 Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, VA Hlth Serv Res & Dev, Natl Ctr Excellence, Bedford, England. Boston Univ, Sch Med, Div Gen Internal Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Hlth Policy & Management Dept, Boston, MA 02215 USA. Philadelphia VAMC, CHERP, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Internal Med, Philadelphia, PA 19104 USA. Jesse Brown VAMC, Chicago, IL USA. Univ Illinois, Chicago, IL 60680 USA. St Louis VAMC, St Louis, MO USA. St Louis Univ, St Louis, MO 63103 USA. RP Kressin, NR (reprint author), Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, VA Hlth Serv Res & Dev, Natl Ctr Excellence, Bedford, England. EM nkressin@bu.edu OI Bokhour, Barbara/0000-0001-8238-0745; Kressin, Nancy/0000-0003-2767-4286 NR 27 TC 52 Z9 52 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2007 VL 22 IS 6 BP 768 EP 774 DI 10.1007/s11606-007-0165-9 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 169AA UT WOS:000246563900009 PM 17364243 ER PT J AU Tsai, CL Griswold, SK Clark, S Camargo, CA AF Tsai, Chu-Lin Griswold, Sharon K. Clark, Sunday Camargo, Carlos A., Jr. TI Factors associated with frequency of emergency department visits for chronic obstructive pulmonary disease exacerbation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; emergency department visits; primary care provider; recurrent exacerbation ID EPIDEMIOLOGIC ANALYSIS; ASTHMA; HOSPITALIZATION; MULTICENTER; PREDICTORS; DECLINE; USERS AB BACKGROUND: Little is known about the factors associated with frequency of emergency department visits (FEDV) in chronic obstructive pulmonary disease (COPD) patients with recurrent exacerbations. OBJECTIVE: To characterize the use of emergency department (ED) services in patients with COPD exacerbation and identify factors associated with FEDV. DESIGN: A prospective, multicenter cohort study. PATIENTS: Three hundred eighty-eight patients were included. Fifty-two percent were women and the median age was 69 years (interquartile range 62-76). MEASUREMENTS: Using a standard questionnaire, consecutive ED patients with COPD exacerbation were interviewed. The number of ED visits in the previous year was retrospectively collected. RESULTS: Over the past year, this cohort reported a total of 1,090 ED visits because of COPD exacerbation. Thirteen percent of COPD patients had 6 or more ED visits, accounting for 57% of the total ED visits in the past year. Multivariate analysis showed that patients with an increased FEDV were more likely to be Hispanic (incidence rate ratio [IRR] 1.97, 95% confidence interval [CI] 1.16-3.33), to have more severe COPD as determined by previous hospitalizations (IRR 2.06, 95% CI 1.51-2.82), prior intubations (IRR 1.49, 95% CI 1.02-2.18), prior use of systemic corticosteroids (IRR 1.57, 95% CI 1.16-2.13) and methylxanthine (IRR 1.48, 95% CI 1.04-2.12), and less likely to have a primary care provider (IRR 0.51, 95% CI 0.31-0.82). CONCLUSIONS: Our results suggest that both disease and health care-related factors were associated with FEDV in COPD exacerbation. Multidisciplinary efforts through primary care provider follow-up should be assessed to test the effects on reducing the high morbidity and cost of recurrent COPD exacerbations. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. Thomas Jefferson Univ Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. RP Tsai, CL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM cltsai@hsph.harvard.edu OI TSAI, CHU-LIN/0000-0003-4639-1513 NR 39 TC 22 Z9 22 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2007 VL 22 IS 6 BP 799 EP 804 DI 10.1007/s11606-007-0191-7 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 169AA UT WOS:000246563900014 PM 17410402 ER PT J AU Tsui, JI Saitz, R Cheng, DM Nunes, D Libman, H Alperen, JK Samet, JH AF Tsui, Judith I. Saitz, Richard Cheng, Debbie M. Nunes, David Libman, Howard Alperen, Julie K. Samet, Jeffrey H. TI Awareness of hepatitis C diagnosis is associated with less alcohol use among persons co-infected with HIV SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 27-29, 2006 CL Los Angeles, CA SP Soc Gen Internal Med DE alcohol; hepatitis C; HIV; awareness of diagnosis ID INJECTION-DRUG USERS; MINI-MENTAL-STATE; VIRUS-INFECTION; CAGE QUESTIONNAIRE; CONSUMPTION; ABUSE; RISK AB BACKGROUND AND OBJECTIVE: It is unknown whether testing HIV-infected individuals for hepatitis C virus (HCV) and informing them of their HCV status impacts subsequent alcohol use. We hypothesized that HIV-infected individuals with current or past alcohol problems who reported being told they had HCV were more likely to 1) abstain from alcohol and 2) not drink unhealthy amounts compared to individuals who had not been told. DESIGN, PARTICIPANTS, AND MEASUREMENTS: Data from a prospective, observational cohort study (HIV-Longitudinal Interrelationships of Viruses and Ethanol) were used to assess the association between awareness of having HCV at baseline and subsequent abstinence and not drinking unhealthy amounts as reported at 6-month follow-up intervals. General estimating equations logistic regression was used to account for the correlation from using repeated observations from the same subject over time. We adjusted for age, sex, race, homelessness, injection drug use, depressive symptoms, and having abnormal liver tests. RESULTS: Participants who reported being told they had HCV were more likely to report abstaining from alcohol (AOR=1.60; 95% CI: 1.13 to 2.27) and not drinking unhealthy amounts (AOR=1.46; 95% CI: 1.01 to 2.11). CONCLUSIONS: Among patients infected with HIV who had a history of alcohol problems, reporting being told one had HCV was associated with greater abstinence from alcohol and less unhealthy amounts of drinking. C1 San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, San Francisco, CA 94121 USA. Boston Med Ctr, Sect Gen Inernal Med, CARE Unit, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Boston Med Ctr, Sch Med, Dept Med,Sect Gastroenterol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Gen Med & Primary Care, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Infect Dis, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA. RP Tsui, JI (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, 4150 Clemont St, San Francisco, CA 94121 USA. EM Judith.Tsui@ucsf.edu OI Samet, Jeffrey/0000-0002-0897-3400; /0000-0002-2535-1427 FU NCRR NIH HHS [KL2 RR024130, KL2 RR024130-01, M01 RR000533, M01 RR000533-385634, M01 RR001032, M01 RR00533, M01 RR01032]; NIAAA NIH HHS [K24 AA015674, K24 AA015674-01A1, R01 AA010870, R01 AA010870-05, R01 AA011785, R01 AA011785-04, R01 AA013216, R01 AA013216-05, R01-AA10870, R01-AA11785, R01-AA13766] NR 20 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2007 VL 22 IS 6 BP 822 EP 825 DI 10.1007/s11606-007-0147-y PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 169AA UT WOS:000246563900018 PM 17503108 ER PT J AU Koya, DL Egede, LE AF Koya, Deepika L. Egede, Leonard E. TI Association between length of residence and cardiovascular disease risk factors among an ethnically diverse group of United States immigrants SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE length of residence; cardiovascular disease; immigrants; race; ethnicity ID CIGARETTE-SMOKING; MORTALITY; HEALTH; ACCULTURATION; HISPANICS; PARADOX; US; RACE/ETHNICITY; BEHAVIORS; NATIVITY AB BACKGROUND: Although differences in cardiovascular disease (CVD) risk factors between immigrants and nonimmigrants have been examined previously, the effect of acculturation on CVD risk factors in immigrants has been less well studied. OBJECTIVE: To determine the association between length of U.S. residence (proxy for acculturation) and major CVD risk factors. METHODS: Data on 5,230 immigrant adults from the 2002 National Health Interview Survey (NHIS) was analyzed. Primary independent variable was length of U.S. residence < 10, 10 to < 15, and >= 15 years. Main outcome measures included obesity, hypertension, diabetes, hyperlipidemia, smoking, and physical inactivity. Multiple logistic regression was used to assess the association between length of residence and odds of multiple CVD risk factors adjusting for confounders. SAS-callable SUDAAN was used for statistical analysis. RESULTS: Among the patients, 55.4% were obese, 17.3% had hypertension, 15.9% had hyperlipidemia, 6.6% had diabetes, 79.3% were physically inactive, and 14.3% were smokers. Using < 10 years as reference, those with length of residence >= 15 years were more likely to be obese (OR 1.31, 95% CI 1.03-1.65), have hyperlipidemia (OR 1.59, 95% CI 1.14-2.22), and be smokers (OR 1.39, 95% CI 1.04-1.85). Length of residence >= 15 years was associated with decreased odds of sedentary lifestyle (OR 0.63, 95% CI 0.47-0.84). Length of residence >= 15 years was not associated with odds of having diabetes (OR 1.40, 95% CI 0.78-2.51) or hypertension (OR 1.21, 95% CI 0.86-1.71). CONCLUSIONS: Among immigrants from diverse ethnic backgrounds, longer length of residence in the United States is associated with increased odds of obesity, hyperlipidemia, and cigarette smoking even after adjusting for relevant confounding factors. C1 Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Hlth Disparities Res, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston VA TREP, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu FU PHS HHS [D55HP05159] NR 29 TC 108 Z9 109 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2007 VL 22 IS 6 BP 841 EP 846 DI 10.1007/s11606-007-0163-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 169AA UT WOS:000246563900022 PM 17503110 ER PT J AU Burgess, D van Ryn, M Dovidio, J Saha, S AF Burgess, Diana van Ryn, Michelle Dovidio, John Saha, Somnath TI Reducing racial bias among health care providers: Lessons from social-cognitive psychology SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE provider behavior; disparities; race; ethnicity; social cognition ID MEDICAL-STUDENTS; PATIENT SATISFACTION; IN-GROUP; PHYSICIAN COMMUNICATION; STEREOTYPE ACTIVATION; CULTURAL COMPETENCE; RACE BIAS; EMPATHY; PREJUDICE; ATTITUDES AB The paper sets forth a set of evidence-based recommendations for interventions to combat unintentional bias among health care providers, drawing upon theory and research in social cognitive psychology. Our primary aim is to provide a framework that outlines strategies and skills, which can be taught to medical trainees and practicing physicians, to prevent unconscious racial attitudes and stereotypes from negatively influencing the course and outcomes of clinical encounters. These strategies and skills are designed to: 1) enhance internal motivation to reduce bias, while avoiding external pressure; 2) increase understanding about the psychological basis of bias; 3) enhance providers' confidence in their ability to successfully interact with socially dissimilar patients; 4) enhance emotional regulation skills; and 5) improve the ability to build partnerships with patients. We emphasize the need for programs to provide a nonthreatening environment in which to practice new skills and the need to avoid making providers ashamed of having racial, ethnic, or cultural stereotypes. These recommendations are also intended to provide a springboard for research on interventions to reduce unintentional racial bias in health care. C1 Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Family Med & Community Hlth, Minneapolis, MN 55455 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. Oregon Hlth & Sci Univ, Sect Gen Internal Med, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. RP Burgess, D (reprint author), Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, 1 Vet Dr, Minneapolis, MN 55417 USA. EM Diana.Burgess@va.gov RI VAN RYN, MICHELLE/B-1664-2010; Burgess, Diana/A-1946-2016 NR 114 TC 120 Z9 121 U1 10 U2 30 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2007 VL 22 IS 6 BP 882 EP 887 DI 10.1007/s11606-007-0160-1 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 169AA UT WOS:000246563900029 PM 17503111 ER PT J AU Nithipongvanitch, R Ittarat, W Velez, JM Zhao, R Clair, DKS Oberley, TD AF Nithipongvanitch, Rarnaneeya Ittarat, Wanida Velez, Joyce M. Zhao, Rui St. Clair, Daret K. Oberley, Terry D. TI Evidence for p53 as guardian of the cardiomyocyte mitochondrial genome following acute adriamycin treatment SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE apoptosis; cardiomyopathy; doxorubicin; mitochondrial DNA; oxidative stress ID INDUCED RENAL CARCINOGENESIS; BASE EXCISION-REPAIR; INDUCED APOPTOSIS; IN-VIVO; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; DNA; CELLS; DOXORUBICIN; TISSUES AB The present study is an initial analysis of whether p53 may function as guardian of the cardiomyocyte mitochondrial genome, with mitochondrial p53 localization proposed to be involved in both mitochondrial DNA (mtDNA) repair and apoptosis. Subcellular distribution, protein levels, and possible function(s) of p53 protein in the response of cardiomyocytes to adriamycin (ADR) were analyzed. Levels and subcellular localization of proteins were determined by Western blot and immunogold ultrastructural analysis techniques. Here we demonstrate that stress caused by ADR induced upregulation of p53 protein in cardiomyocyte mitochondria and nuclei between 3 and 24 hr. Increased expression of PUMA and Bax proteins, pro-apoptotic targets of p53, was documented following ADR treatment and was accompanied by increased levels of apoptotic markers, with elevation of cytosolic cytochrome c at 24 hr and subsequent caspase-3 cleavage at 3 days. Mitochondrial p53 levels correlated with mtDNA oxidative damage. Loss of p53 in knockout mouse heart resulted in a significant increase in mtDNA vulnerability to damage following ADR treatment. Our results suggest that mitochondrial p53 could participate in mtDNA repair as a first response to oxidative damage of cardiomyocyte mtDNA and demonstrate an increase of apoptotic markers as a result of mitochondrial/nuclear p53 localization. C1 William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, Madison, WI 53705 USA. Univ Kentucky, Dept Toxicol, Lexington, KY USA. Mahidol Univ, Fac Med Technol, Bangkok 10700, Thailand. Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Pathol & Lab Med, Room A-35,2500 Overlook Terrace, Madison, WI 53705 USA. EM dstcl00@pop.uky.edu; toberley@wisc.edu FU NCI NIH HHS [CA-94853] NR 44 TC 40 Z9 40 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 EI 1551-5044 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUN PY 2007 VL 55 IS 6 BP 629 EP 639 DI 10.1369/jhc.6A7146.2007 PG 11 WC Cell Biology SC Cell Biology GA 170CW UT WOS:000246640500010 PM 17312011 ER PT J AU Brown, S Kurtsikashvili, G Alonso-Echanove, J Ghadua, M Ahmeteli, L Bochoidze, T Shushtakashvili, M Eremin, S Tsertsvadze, E Imnadze, P O'Rourke, E AF Brown, S. Kurtsikashvili, G. Alonso-Echanove, J. Ghadua, M. Ahmeteli, L. Bochoidze, T. Shushtakashvili, M. Eremin, S. Tsertsvadze, E. Imnadze, P. O'Rourke, E. TI Prevalence and predictors of surgical site infection in Tbilisi, Republic of Georgia SO JOURNAL OF HOSPITAL INFECTION LA English DT Article DE surgical site infection; epidemiology; prophylaxis ID NOSOCOMIAL INFECTIONS; WOUND INFECTIONS; DEVELOPING-COUNTRY; ANTIBIOTIC-PROPHYLAXIS; SURVEILLANCE METHODS; HAIR-REMOVAL; CARE; PREVENTION; RATES; DEFINITIONS AB Surgical site infections (SSIs) are a serious problem worldwide. Little is known about the epidemiology of SSI in the former Soviet Union. In order to determine the prevalence and predictors of SSI in the Republic of Georgia, we undertook a multicentre observational study of SSIs in three urban hospitals in the capital., Tbilisi. Point prevalence studies (PPS) were performed every 3-5 weeks from September 2000 to January 2002 using the National Nosocomial Infections Surveillance (NNIS) System definitions. All patients who had undergone surgery and were present in participating departments at study hospitals on the day of PPS were included. Of 872 surgical procedures, 146 (16.7%) were complicated by SSI. The prevalence of SSI varied by procedure and risk category. On multivariate regression analysis, age, wound class, one hospital (B) and urological surgery were predictive of SSI. In a separate model., NNIS risk index was highly predictive of SSI. Antibiotic prophylaxis was rare (29.5% of operations), while postoperative antibiotic use was common. SSI is an important problem in the Republic of Georgia. Potential areas for intervention include antibiotic prophylaxis and shaving practices for skin preparation. (C) 2007 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Natl Ctr Dis Control, Tbilisi, Rep of Georgia. CDC, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. Tbilisi State Univ, Tbilisi, Rep of Georgia. Natl Ctr Surg, Tbilisi, Rep of Georgia. Mechnikov State Med Acad, St Petersburg, Russia. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA USA. RP Brown, S (reprint author), Univ Utah, Hlth Sci Ctr, Div Resp Crit Care & Occupat Pulm Med, Wintrobe 701,26 N 1900 E, Salt Lake City, UT 84132 USA. EM Samuel.Brown@hsc.utah.edu OI Eremin, Sergey/0000-0002-0486-3255 NR 35 TC 10 Z9 12 U1 3 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-6701 J9 J HOSP INFECT JI J. Hosp. Infect. PD JUN PY 2007 VL 66 IS 2 BP 160 EP 166 DI 10.1016/j.jhin.2007.03.007 PG 7 WC Infectious Diseases SC Infectious Diseases GA 185PX UT WOS:000247724000010 PM 17513010 ER PT J AU Wong, J Obst, R Correia-Neves, M Losyev, G Mathis, D Benoist, C AF Wong, Jamie Obst, Reinhard Correia-Neves, Margarida Losyev, Grigoriy Mathis, Diane Benoist, Christophe TI Adaptation of TCR repertoires to self-peptides in regulatory and nonregulatory CD4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; SINGLE MHC/PEPTIDE LIGAND; NEGATIVE SELECTION; CLONAL DELETION; ANTIGEN PRESENTATION; IN-VIVO; MICE; EXPRESSION; TOLERANCE; INDUCTION AB Currently, it is not understood how the specificity of the TCR guides CD4(+) T cells into the conventional lineage (Tconv) vs directing them to become regulatory (Treg) cells defined by the Foxp3 transcription factor. To address this question, we made use of the "Limited" (LTD) mouse, which has a restricted TCR repertoire with a fixed TCR beta chain and a TCR alpha chain minilocus. The TCR repertoires of Tconv and Treg cells were equally broad, were distinct, yet overlapped significantly, representing a less strict partition than previously seen between CD4 and CD8 T cells. As a group, the CDR3 alpha motifs showed a significant trend to higher positive charge in Treg than in Tconv cells. The Tconv and Treg repertoires were both reshaped between thymus and periphery. Reducing the array of peptides presented by MHC class II molecules by introducing the H2-DMo/o mutation into the LTD mouse led to parallel shifts in the repertoires of Tconv and Treg cells. In both cases, the CDR3a elements were entirely different and strikingly shortened, relative to normal LTD mice. These peculiar sequences conferred reactivity to wild-type MHC class II complexes and were excluded from the normal repertoire, even among Treg cells, indicating that some forms of self-reactivity are incompatible with selection into the Treg lineage. In conclusion, the Treg repertoire is broad, with distinct composition and characteristics, yet significantly overlapping and sharing structural constraints with the repertoire of conventional CD4(+) T cells. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr,Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu RI Correia-Neves, Margarida/C-9122-2009 OI Correia-Neves, Margarida/0000-0002-2202-5431 FU NIAID NIH HHS [R01 AI51530] NR 56 TC 112 Z9 114 U1 2 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2007 VL 178 IS 11 BP 7032 EP 7041 PG 10 WC Immunology SC Immunology GA 173TV UT WOS:000246896300044 PM 17513752 ER PT J AU Vyas, JM Kim, YM Artavanis-Tsakonas, K Love, JC Van der Veen, AG Ploegh, HL AF Vyas, Jatin M. Kim, You-Me Artavanis-Tsakonas, Katerina Love, J. Christopher Van der Veen, Annemarthe G. Ploegh, Hidde L. TI Tubulation of class II MHC compartments is microtubule dependent and involves multiple endolysosomal membrane proteins in primary dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; IMMUNOLOGICAL SYNAPSE; INVARIANT CHAIN; TETRASPAN MICRODOMAINS; MULTIVESICULAR BODIES; ANTIGEN PRESENTATION; CUTTING EDGE; MATURATION; TRANSPORT; LYSOSOMES AB Immature dendritic cells (DCs) capture exogenous Ags in the periphery for eventual processing in endolysosomes. Upon maturation by TLR agonists, DCs deliver peptide-loaded class II MHC molecules from these compartments to the cell surface via long tubular structures (endolysosomal tubules). The nature and rules that govern the movement of these DC compartments are unknown. In this study, we demonstrate that the tubules contain multiple proteins including the class II MHC molecules and LAMP1, a lysosomal resident protein, as well as CD63 and CD82, members of the tetraspanin family. Endolysosomal tubules can be stained with acidotropic dyes, indicating that they are extensions of lysosomes. However, the proper trafficking of class II MHC molecules themselves is not necessary for endolysosomal tubule formation. DCs lacking MyD88 can also form endolysosomal tubules, demonstrating that MyD88-dependent TLR activation is not necessary for the formation of this compartment. Endolysosomal tubules in DCs exhibit dynamic and saltatory movement, including bidirectional travel. Measured velocities are consistent with motor-based movement along microtubules. Indeed, nocodazole causes the collapse of endolysosomal tubules. In addition to its association with microtubules, endolysosomal tubules follow the plus ends of microtubules as visualized in primary DCs expressing end binding protein 1 (EB1)-enhanced GFP. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. CBR, Inst Biomed Res, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Vyas, JM (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM jvyas@partners.org RI Kim, You-Me/I-5553-2013; Vyas, Jatin/Q-1627-2016 OI Kim, You-Me/0000-0001-8780-704X; Vyas, Jatin/0000-0002-9985-9565 FU NCI NIH HHS [F32 CA105862, 1F32CA105862-01]; NIAID NIH HHS [5K08AI057999, 5R01AI034893-13, K08 AI057999, K08 AI057999-04, R01 AI034893] NR 58 TC 60 Z9 60 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2007 VL 178 IS 11 BP 7199 EP 7210 PG 12 WC Immunology SC Immunology GA 173TV UT WOS:000246896300061 PM 17513769 ER PT J AU Aujesky, D Perrier, A Roy, PM Stone, RA Cornuz, J Meyer, G Obrosky, DS Fine, MJ AF Aujesky, D. Perrier, A. Roy, P.-M. Stone, R. A. Cornuz, J. Meyer, G. Obrosky, D. S. Fine, M. J. TI Validation of a clinical prognostic model to identify low-risk patients with pulmonary embolism SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE mortality; prognostic model; pulmonary embolism; validation ID MOLECULAR-WEIGHT HEPARIN; RIGHT-VENTRICULAR DYSFUNCTION; HELICAL COMPUTED-TOMOGRAPHY; OUTPATIENT TREATMENT; CONTROLLED-TRIALS; PREDICTION RULE; MANAGEMENT; METAANALYSIS; GUIDELINES; THROMBOSIS AB Objective. To validate the Pulmonary Embolism Severity Index (PESI), a clinical prognostic model which identifies low-risk patients with pulmonary embolism (PE). Design. Validation study using prospectively collected data. Setting. A total of 119 European hospitals. Subjects. A total of 899 patients diagnosed with PE. Intervention. The PESI uses 11 clinical factors to stratify patients with PE into five classes (I-V) of increasing risk of mortality. We calculated the PESI risk class for each patient and the proportion of patients classified as low-risk (classes I and II). The outcomes were overall and PE-specific mortality for low-risk patients at 3 months after presentation. We calculated the sensitivity, specificity and predictive values to predict overall and PE-specific mortality and the discriminatory power using the area under the receiver operating characteristic curve. Results. Overall and PE-specific mortality was 6.5% (58/899) and 2.3% (21/899) respectively. Forty-seven per cent of patients (426/899) were classified as low-risk. Low-risk patients had an overall mortality of only 1.2% (5/426) and a PE-specific mortality of 0.7% (3/426). The sensitivity was 91 [95% confidence interval (CI): 81-97%] and the negative predictive value was 99% (95% CI: 97-100%) for overall mortality. The sensitivity was 86% (95% CI: 64-97%) and the negative predictive value was 99% (95% CI: 98-100%) for PE-specific mortality. The areas under the receiver operating characteristic curve for overall and PE-specific mortality were 0.80 (95% CI: 0.75-0.86) and 0.77 (95% CI: 0.68-0.86) respectively. Conclusions. This validation study confirms that the PESI reliably identifies low-risk patients with PE who are potential candidates for less costly outpatient treatment. C1 Univ Lausanne, Univ Outpatient Clin, Div Gen Internal Med, CH-1015 Lausanne, Switzerland. Univ Lausanne, Clin Epidemiol Ctr, CH-1015 Lausanne, Switzerland. Univ Geneva, Div Gen Internal Med, CH-1211 Geneva, Switzerland. Univ Angers, Dept Emergency Med, Angers, France. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA. VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Hop Europeen Georges Pompidou, Dept Resp & Crit Care Med, Paris, France. Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. RP Aujesky, D (reprint author), CHU Vaudois, Serv Med Interne, BH 10-622, CH-1011 Lausanne, Switzerland. EM drahomir.aujesky@chuv.ch RI Perrier, Arnaud/M-2263-2014 FU NIAID NIH HHS [K24AI01769] NR 31 TC 69 Z9 70 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JUN PY 2007 VL 261 IS 6 BP 597 EP 604 DI 10.1111/j.1365-2796.2007.01785.x PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 172KO UT WOS:000246803400008 PM 17547715 ER PT J AU Ho, I Heist, EK Aryana, A Mela, T d'Avila, A Ruskin, J Mansour, M AF Ho, Ivan Heist, E. Kevin Aryana, Arash Mela, Theofanie d'Avila, Andre Ruskin, Jeremy Mansour, Moussa TI Compression of the left atrium by the thoracic aorta in patients undergoing pulmonary vein isolation procedure for atrial fibrillation SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; catheter ablation; MRI; pulmonary vein stenosis; compression ID MAGNETIC-RESONANCE ANGIOGRAPHY; GUIDE CATHETER ABLATION; COMPUTED-TOMOGRAPHY; OSTIAL ABLATION; INTEGRATION; ANATOMY; ANEURYSM; IMAGES AB Introduction With the increasing use of pre-procedural imaging techniques such as magnetic resonance imaging (MRI) and their integration with electroanatomic mapping systems in catheter ablation for atrial fibrillation (AF), atypical anatomy of the pulmonary veins (PV), left atrium (LA) and their relationship to the thoracic aorta is increasingly recognized. Objective To characterize atypical LA-PV anatomies revealed by pre-procedural MRI and their impact on the safety and efficacy of AF ablation procedures. Materials and methods We reported four patients who underwent AF ablation in our electrophysiology laboratory within the last year who had atypical LA-PV anatomy due to aorta compression recognized by pre-procedural three-dimensional (3D) MRI and anatomic segmentation. Twelve matched control cases without aorta compression were selected for comparison of LA-PV measurements. Results All four patients in this study had a normal-sized descending thoracic aorta that compressed the left atrium, and all patients had evidence of left inferior PV narrowing secondary to external compression. Two patients also had anterior LA compression leading to posteriorly displaced interatrial septum. Isolation was not achieved in some PVs due to anatomic restraints, concern regarding risks of aortic injury and worsening pulmonary vein stenosis. There were no immediate or short-term complications. Conclusions Extrinsic compression by the descending aorta on the LA and PV leading to LA compression and/or preexisting PV stenosis is uncommon but has potentially important implications on the overall safety and efficacy of AF ablation procedures. Pre-procedural imaging plays an important role in assessing such anatomic variations and planning of the procedures in order to minimize the risk of PV stenosis and aortic injury. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,Gray 109, Boston, MA 02114 USA. EM mmansour@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 20 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD JUN PY 2007 VL 19 IS 1 BP 29 EP 36 DI 10.1007/s10840-007-9134-9 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 194YV UT WOS:000248380600004 PM 17610054 ER PT J AU Chren, MM Sahay, AP Bertenthal, DS Sen, S Landefeld, CS AF Chren, Mary-Margaret Sahay, Anju P. Bertenthal, Daniel S. Sen, Saunak Landefeld, C. Seth TI Quality-of-life outcomes of treatments for cutaneous basal cell carcinoma and squamous cell carcinoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MOHS MICROGRAPHIC SURGERY; NONMELANOMA SKIN-CANCER; TREATMENT MODALITIES; SURGICAL EXCISION; FACE; QUESTIONNAIRE; MEDICARE AB Quality of life is an important treatment outcome for conditions that are rarely fatal, such as cutaneous basal cell carcinoma and squamous cell carcinoma (typically called nonmelanoma skin cancer (NMSC)). The purpose of this study was to compare quality-of-life outcomes of treatments for NMSC. We performed a prospective cohort study of 633 consecutive patients with NMSC diagnosed in 1999 and 2000 and followed for 2 years after treatment at a university-based private practice or a Veterans Affairs clinic. The main outcome was tumor-related quality of life 1 to 2 years after therapy, measured with the 16-item version of Skindex, a validated measure. Skindex scores vary from 0 (best) to 100 (worst) in three domains: Symptoms, Emotions, and Function. Treatments were electrodessication and curettage (ED&C) in 21%, surgical excision in 40%, and Mohs surgery in 39%. Five hundred and eight patients (80%) responded after treatment. Patients treated with excision or Mohs surgery improved in all quality-of-life domains, but quality of life did not improve after ED&C. There was no difference in the amount of improvement after excision or Mohs surgery. For example, mean Skindex Symptom scores improved 9.7 (95% Cl: 6.9, 12.5) after excision, 10.2 (7.4, 12.9) after Mohs surgery, and 3.4 (-0.9, 7.6) after ED&C. We conclude that, for NMSC, quality-of-life outcomes were similar after excision and Mohs surgery, and both therapies had better outcomes than ED&C. C1 Univ Calif San Francisco, San Francisco VAMC, Dermatol Serv, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Vet Affairs, San Francisco, CA 94121 USA. Vet Affairs Med Ctr, Hlth Serv Res Enhancement Award Program, REAP, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Geriatr & Extended Care Serv, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. RP Chren, MM (reprint author), Univ Calif San Francisco, San Francisco VAMC, Dermatol Serv, 151R,4150 Clement St, San Francisco, CA 94121 USA. EM chrenm@derm.ucsf.edu FU NIAMS NIH HHS [K02 AR 02203-01] NR 29 TC 46 Z9 46 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 2007 VL 127 IS 6 BP 1351 EP 1357 DI 10.1038/sj.jid.5700740 PG 7 WC Dermatology SC Dermatology GA 169UT UT WOS:000246618300013 PM 17301830 ER PT J AU Moller-Kristensen, M Hamblin, MR Thiel, S Jensenius, JC Takahashi, K AF Moller-Kristensen, Mette Hamblin, Michael R. Thiel, Steffen Jensenius, Jens Chr. Takahashi, Kazue TI Burn injury reveals altered phenotype in mannan-binding lectin-deficient mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CHEMOATTRACTANT PROTEIN-1 MCP-1; ACUTE-PHASE RESPONSE; GROWTH-FACTOR I; THERMAL-INJURY; MATRIX METALLOPROTEINASES; COMPLEMENT PATHWAY; ENDOTHELIAL-CELLS; SERINE-PROTEASE; DIFFERENTIAL EXPRESSION; STAPHYLOCOCCUS-AUREUS AB Burn injury destroys skin, the second largest innate immune organ in the body, and triggers chaotic immune and inflammatory responses. The pattern recognition molecule, mannan-binding lectin (MBL), plays an important role in the first-line host defense against infectious agents. MBL initiates the lectin complement pathway and acts as an opsonin. Recent studies suggest that MBL also modulates inflammatory responses. We report that local responses after burn in MBL null mice differ from those found in wild-type (WT) mice in the following important biological markers: spontaneous eschar separation, thinned epidermis and dermis, upregulation of soluble factors including cytokines, chemokines, cell adhesion molecules, a growth factorbinding protein, and matrix metal loprotei nases. Mice lacking C1q, C4, or C3 did not show the lack of eschar separation seen in MBL null-burn phenotype. These findings implicate MBL as an important molecule in the maintenance of the homeostatic balance. C1 Harvard Univ, Sch Med, Lab Dev Immunol, Dept Pediat, Boston, MA 02115 USA. Univ Aarhus, Dept Med Microbiol & Immunol, Aarhus C, Denmark. Harvard Univ, Sch Med, Wellman Ctr Photomed, Dept Dermatol,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Takahashi, K (reprint author), 55 Fruit St,GRJ1402, Boston, MA 02114 USA. EM ktakahashi1@partners.org OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01 AI050875-05A1] NR 73 TC 20 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 2007 VL 127 IS 6 BP 1524 EP 1531 DI 10.1038/sj.jid.5700748 PG 8 WC Dermatology SC Dermatology GA 169UT UT WOS:000246618300035 PM 17363917 ER PT J AU Andersson, KB Finsen, AV Sjaastad, I Wang, Y Chen, J Molkentin, JD Chien, KR Sejersted, OM Christensen, G AF Andersson, Kristin B. Finsen, Alexandra V. Sjaastad, Ivar Wang, Yibin Chen, Ju Molkentin, Jeffery D. Chien, Kenneth R. Sejersted, Ole M. Christensen, Geir TI Heart function in adult cardiac Serca2(null) mice SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 19th World Congress of the International-Society-for-Heart-Research CY JUN 22-25, 2007 CL Bologna, ITALY SP Int Soc Heart Res DE calcium handling; sarcoplasmatic reticulum; cardiac function C1 Univ Oslo, N-0316 Oslo, Norway. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUN PY 2007 VL 42 SU 1 BP S106 EP S106 DI 10.1016/j.yjmcc.2007.03.237 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 184UV UT WOS:000247669000291 ER PT J AU Lessell, S Kim, JW Hatton, MP Stemmer-Rachamimov, A Thiagalingham, S Rubin, PAD AF Lessell, Simmons Kim, Jonathan W. Hatton, Mark P. Stemmer-Rachamimov, Anat Thiagalingham, Sureka Rubin, Peter A. D. TI Clinical without histopathological manifestations of inflammation in a patient with primary intraorbital optic nerve sheath meningioma SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article AB A 28-year-old mart with a biopsy-proven benign intraorbital optic nerve sheath meningioma developed recurrent clinical manifestations of ipsilateral retrobulbar inflammation 9 years after undergoing postoperative radiation therapy. Debulking of the tumor 11 years after the original surgery again revealed no pathologic signs of inflammation. Whether growth of tumor, surgery, radiation, or edema triggered the inflammatory manifestations is unclear. Our case affirms that primary optic nerve meningiomas may rarely cause episodic manifestations resembling those of idiopathic orbital inflammation that resolve with corticosteroid treatment. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. RP Lessell, S (reprint author), 243 Charles St, Boston, MA 02114 USA. EM simmons_lessell@meei.harvard.edu NR 5 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD JUN PY 2007 VL 27 IS 2 BP 104 EP 106 DI 10.1097/WNO.0b013e318064e495 PG 3 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 175NV UT WOS:000247021200005 PM 17548993 ER PT J AU Herrmann, P Druckrey-Fiskaan, C Bigl, M Cotman, SL Schliebs, R AF Herrmann, P. Druckrey-Fiskaan, C. Bigl, M. Cotman, S. L. Schliebs, R. TI Developmental impairments of select neurotransmitter systems in brains of CLN3-ki mice, an animal model of juvenile neuronal lipofuscinosis SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 17th European-Society-for-Neurochemistry Meeting/3rd Conference on Advances in Molecular Mechanisms of Neurological Disorder CY MAY 19-22, 2007 CL Salamanca, SPAIN SP European Soc Neurochem C1 Univ Leipzig, Paul Flechsig Inst Brain Res, Dept Neurochem, D-7010 Leipzig, Germany. Univ Leipzig, Fac Med, Inst Biochem, Dept Mol Biol, D-7010 Leipzig, Germany. Massachusetts Gen Hosp, Ctr Human Genet Res, Simches Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2007 VL 101 SU 1 BP 67 EP 68 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 160ZT UT WOS:000245984800189 ER PT J AU Denny, CA Alroy, J Pawlyk, BS Sandberg, MA d'Azzo, A Seyfried, TN AF Denny, Christine A. Alroy, Joseph Pawlyk, Basil S. Sandberg, Michael A. d'Azzo, Alessandra Seyfried, Thomas N. TI Neurochemical, morphological, and neurophysiological abnormalities in retinas of Sandhoff and GM1 gangliosidosis mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE electroretinograms; GA1; GA2; GD3; GM1; GM2; Sandhoff Disease; visual evoked potentials ID DISEASE GM2-GANGLIOSIDOSIS TYPE-2; THIN-LAYER CHROMATOGRAPHY; ACID BETA-GALACTOSIDASE; MUTANT MICE; MOUSE MODELS; BRAIN-STEM; TAY-SACHS; CEREBELLAR; DEGENERATION; GD3 AB Retinal abnormalities are well documented in patients with ganglioside storage diseases. The total content and distribution of retinal glycosphingolipids was studied for the first time in control mice and in Sandhoff disease (SD) and GM1 gangliosidosis mice. Light and electron microscopy of the SD and the GM1 retinas revealed storage in ganglion cells. Similar to previous findings in rat retina, GD3 was the major ganglioside in mouse retina, while GM2 and GM1 were minor species. Total ganglioside content was 44% and 40% higher in the SD and the GM1 retinas, respectively, than in the control retinas. Furthermore, GM2 and GM1 content were 11-fold and 51-fold higher in the SD and the GM1 retinas than in the control retinas, respectively. High concentrations of asialo-GM2 and asialo-GM1 were found in the SD and the GM1 retinas, respectively, but were undetectable in the control retinas. The GSL abnormalities in the SD and the GM1 retinas reflect significant reductions in beta-hexosaminidase and beta-galactosidase enzyme activities, respectively. Although electroretinograms appeared normal in the SD and the GM1 mice, visual evoked potentials were subnormal in both mutants, indicating visual impairments. Our findings present a model system for assessing retinal pathobiology and therapies for the gangliosidoses. C1 Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. Tufts Univ, Dept Pathol, Sch Med, Boston, MA 02111 USA. Tufts Univ, Dept Pathol, Sch Vet Med, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. St Jude Childrens Hosp, Dept Genet, Memphis, TN 38105 USA. RP Seyfried, TN (reprint author), Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. EM thomas.seyfried@bc.edu RI Denny, Christine Ann/I-5235-2015; OI Denny, Christine Ann/0000-0002-6926-2020; Seyfried, Thomas/0000-0003-1491-3989 FU NEI NIH HHS [EY016350]; NICHD NIH HHS [HD39722]; NIDDK NIH HHS [R01-DK52025] NR 41 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2007 VL 101 IS 5 BP 1294 EP 1302 DI 10.1111/j.1471-4159.2007.04525.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 166GF UT WOS:000246365600014 PM 17442056 ER PT J AU Bohnen, NI Kaufer, DI Hendrickson, R Constantine, GM Mathis, CA Moore, RY AF Bohnen, N. I. Kaufer, D. I. Hendrickson, R. Constantine, G. M. Mathis, C. A. Moore, R. Y. TI Cortical cholinergic denervation is associated with depressive symptoms in Parkinson's disease and parkinsonian dementia SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID ALZHEIMER AB Aim: To investigate the relationship between ratings of depressive symptoms and in vivo cortical acetylcholinesterase (AChE) activity in subjects with Parkinson's disease (PD) and parkinsonian dementia (PDem). Methods: Subjects (with PD, n = 18, including subjects with PDem, n = 6, and normal controls, n = 10) underwent [C-11] methyl-4-piperidinyl propionate AChE positron emission tomography imaging and clinical assessment including the Cornell Scale for Depression in Dementia (CSDD). Results: Subjects with PD and PDem had higher scores on the CSDD compared with normal controls: 7.3 (5.4) and 2.8 (2.6), respectively (F = 6.9, p = 0.01). Pooled analysis demonstrated a significant inverse correlation between cortical AChE activity and CSDD scores: R = 20.5, p = 0.007. This correlation remained significant after controlling for Mini-Mental State Examination scores. Conclusion: Depressive symptomatology is associated with cortical cholinergic denervation in PD that tends to be more prominent when dementia is present. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Math & Stat, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Bohnen, NI (reprint author), Univ Michigan, Med Ctr, Dept Radiol, Div Nucl Med,Univ Hosp, B1 G505,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM nbohnen@umich.edu RI Mathis, Chester/A-8607-2009 FU NIA NIH HHS [AG-05133] NR 18 TC 48 Z9 49 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUN PY 2007 VL 78 IS 6 BP 641 EP 643 DI 10.1136/jnnp.2006.100073 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 169LO UT WOS:000246593900024 PM 17507447 ER PT J AU Behn, CGD Brown, EN Scammell, TE Kopell, NJ AF Behn, Cecilia G. Diniz Brown, Emery N. Scammell, Thomas E. Kopell, Nancy J. TI Mathematical model of network dynamics governing mouse sleep-wake Behavior SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VENTROLATERAL PREOPTIC NUCLEUS; HISTAMINERGIC TUBEROMAMMILLARY NEURONS; LOCUS COERULEUS NEURONS; DORSAL RAPHE NEURONS; REM-SLEEP; GALANINERGIC NEURONS; CHOLINERGIC NUCLEI; PARADOXICAL SLEEP; WAKING CYCLE; ADENOSINE AB Recent work in experimental neurophysiology has identified distinct neuronal populations in the rodent brain stem and hypothalamus that selectively promote wake and sleep. Mutual inhibition between these cell groups has suggested the conceptual model of a sleep-wake switch that controls transitions between wake and sleep while minimizing time spent in intermediate states. By combining wake- and sleep-active populations with populations governing transitions between different stages of sleep, a "sleep-wake network" of neuronal populations may be defined. To better understand the dynamics inherent in this network, we created a model sleep-wake network composed of coupled relaxation oscillation equations. Mathematical analysis of the deterministic model provides insight into the dynamics underlying state transitions and predicts mechanisms for each transition type. With the addition of noise, the simulated sleep-wake behavior generated by the model reproduces many qualitative and quantitative features of mouse sleep wake behavior. In particular, the existence of simulated brief awakenings is a unique feature of the model. In addition to capturing the experimentally observed qualitative difference between brief and sustained wake bouts, the model suggests distinct network mechanisms for the two types of wakefulness. Because circadian and other factors alter the fine architecture of sleep-wake behavior, this model provides a novel framework to explore dynamical principles that may underlie normal and pathologic sleep-wake physiology. C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Boston Univ, Ctr BioDynam, Dept Math, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. RP Behn, CGD (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cbehn@bidmc.harvard.edu RI Diniz Behn, Cecilia/L-1643-2013 FU NHLBI NIH HHS [P50 HL060292, HL-60292, P50 HL060292-090005]; NIMH NIH HHS [MH-62589, R01 MH062589, R01 MH062589-05]; PHS HHS [DAO-15644] NR 62 TC 51 Z9 51 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 2007 VL 97 IS 6 BP 3828 EP 3840 DI 10.1152/jn.01184.2006 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 188RY UT WOS:000247938200002 PM 17409167 ER PT J AU Susarla, SM Kaban, LB Donoff, RB Dodson, TB AF Susarla, Srinivas M. Kaban, Leonard B. Donoff, R. Bruce Dodson, Thomas B. TI Does early repair of lingual nerve injuries improve functional sensory recovery? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID PATIENT SATISFACTION; MANAGEMENT AB Purpose: This study evaluated the relationship between timing of lingual nerve repair and functional sensory recovery. Materials and Methods: Using a retrospective cohort study design, the investigators enrolled a sample of subjects who had lingual nerve repair. The predictor variable was time between injury and repair, categorized as early (< 90 days after injury) or late (> 90 days after injury). The outcome variable was the time to functional sensory recovery (FSR), measured in days. Other variables were categorized as demographic, anatomic, and operative. Uni- and multivariate Cox proportional hazards models were used to evaluate the association between the timing of the repair and time to FSR. Results: The study sample was composed of 64 subjects who had lingual nerve repair between January 1998 and January 2005. The mean time between injury and repair was 153.2 (31-1606) days; 21.9% of subjects had early repair. The mean age was 28.4 +/- 8.0 years, 62.5% of subjects were female; 77% of the injured nerves were repaired by direct suture, and 23% had surgical exploration with decompression/ neurolysis. In bivariate analyses, early repair, method of repair, and neuroma were statistically or near-statistically associated with time to FSR (P <= .12). In a multiple Cox proportional hazards model, early repair was associated with time to FSR (P = .02). Ninety-three percent of subjects in the early repair group achieved FSR within 1 year, compared with 62.9% in the late group (P =.05). Conclusions: Early repair of lingual nerve injuries results in FSR more frequently and earlier than late repair. (c) 2007 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Ctr Appl Clin Invest, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Ctr Appl Clin Invest, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM tbdodson@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 NR 16 TC 25 Z9 25 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2007 VL 65 IS 6 BP 1070 EP 1076 DI 10.1016/j.joms.2006.10.010 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 174HF UT WOS:000246932100003 PM 17517288 ER PT J AU Lazarski, MP Susarla, SM Bennett, NL Seldin, EB AF Lazarski, Michael P. Susarla, Srinivas M. Bennett, Nancy L. Seldin, Edward B. TI How do feedback and instructions affect the performance of a simulated surgical task? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID VIRTUAL-REALITY-SIMULATOR; VERTICAL RAMUS OSTEOTOMY; SKILLS; SURGERY; REPAIR AB Purpose: This study was conducted to objectively evaluate the effect of feedback and instructional material on the acquisition of surgical psychomotor skills for a model system based on mandibular fracture repair. Materials and Methods: This study was a prospective cohort study comprised of students in the preclinical years of dental or medical education. The students were divided into 4 groups and exposed to different levels of feedback/written instructions (including none) in the testing environment. Each subject was given a pair of aluminum bars, representing a fractured human mandible, and a standardized set of tools, including a fixed length of stainless steel wire to fix the bars together. The strength of fixation was measured, using a calibrated testing apparatus, as the amount of load that the fixed sample could tolerate to the point of failure. All subjects completed 5 successive trials under the same conditions. Descriptive statistics were recorded to provide comparisons between groups. Bivariate statistics were computed to compare the different study groups; multiple-comparison testing was used to evaluate differences among the groups. A P value <= 05 was considered statistically significant. Results: The sample was comprised of 61 students, divided into 4 groups. The students who received neither instructions nor feedback had the lowest average performance scores. Those who received both feedback and instructions had the highest average performance scores. The students who received instructions only fared better than those who received feedback only, but only immediately after receiving instructions. Differences between the groups tended to dissipate after a few trials. Conclusions: Written instructions and performance feedback can enhance the acquisition of psychomotor skifls related to the performance of a complex task. (c) 2007 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Res & Educ Fund, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Continuing Educ, Boston, MA USA. RP Seldin, EB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Res & Educ Fund, 55 Fruit St,Warren 201, Boston, MA 02114 USA. EM eseldin@partners.org OI Susarla, Srinivas/0000-0003-0155-8260 NR 13 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2007 VL 65 IS 6 BP 1155 EP 1161 DI 10.1016/j.joms.2006.11.021 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 174HF UT WOS:000246932100015 PM 17517300 ER PT J AU Ferrell, B Connor, SR Cordes, A Dahlin, CM Fine, PG Hutton, N Leenay, M Lentz, J Person, JL Meier, DE Zuroski, K AF Ferrell, Betty Connor, Stephen R. Cordes, Anne Dahlin, Constance M. Fine, Perry G. Hutton, Nancy Leenay, Mark Lentz, Judy Person, Judi Lund Meier, Diane E. Zuroski, Ken CA Natl Consensus Project Quality Pal TI The national agenda for quality palliative care: The National Consensus Project and the National Quality Forum SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE palliative care AB The release in 2007 of the National Quality Forum (NQF) preferred practices is a significant advance in the field of palliative care. These NQF, preferred practices build on the clinical practice guidelines for palliative care developed by the National Consensus Project (NCP). The NQF is dedicated to improving the quality of American health care, and their focus on palliative care recognizes its g-rowing place within the broader scope of health care. This article reviews the work of both the NCP and NQF and presents the domains and preferred practices that should guide quality improvement efforts in hospice and palliative care. C1 City Hope Natl Med Ctr, Duarte, CA 91010 USA. Natl Hospice & Palliat Care Org, Alexandria, VA USA. Amer Acad Hospice & Palliat Med, Glenview, IL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Johns Hopkins Childrens Ctr, Baltimore, MD USA. Univ Minnesota, Sch Med, Dept Family Med & Community Hlth, Minneapolis, MN USA. Hospice & Palliat Nurses Assoc, Pittsburgh, PA USA. Mt Sinai Sch Med, Ctr Adv Palliat Care, Lilian & Benjamin Hertzberg Palliat Care Inst, Dept Geriatr Med, New York, NY USA. Natl Consesus Project, Pittsburgh, PA USA. RP Ferrell, B (reprint author), City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM bferrell@coh.org OI Connor, Stephen/0000-0003-0332-2067 NR 2 TC 74 Z9 75 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUN PY 2007 VL 33 IS 6 BP 737 EP 744 DI 10.1016/j.jpainsymman.2007.02.024 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 176XX UT WOS:000247119300012 PM 17531914 ER PT J AU Kunisaki, SM Armant, M Kao, GS Stevenson, K Kim, H Fauza, DO AF Kunisaki, Shaun M. Armant, Myriam Kao, Grace S. Stevenson, Kristen Kim, Haesook Fauza, Dario O. TI Tissue engineering from human mesenchymal amniocytes: a prelude to clinical trials SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the American-Academy-of-Pediatrics CY OCT 07-10, 2006 CL Atlanta, GA SP Amer Acad Pediat DE mesenchymal stem cells; fetal cells; amniocytes; amniotic fluid; tissue engineering; cell therapy; human serum; fetal bovine serum ID AMNIOTIC-FLUID CELLS; STEM-CELLS; OSTEOGENESIS IMPERFECTA; CULTURE; REPAIR; TRANSPLANTATION; RECONSTRUCTION; ENGRAFTMENT; RECOVERY; PATIENT AB Purpose: The surgical treatment of congenital anomalies using tissues engineered from amniotic fluid-derived mesenchymal cells has been validated experimentally. As a prerequisite for testing the clinical feasibility of this therapeutic concept, this study was aimed to expand human mesenchymal amniocytes in the absence of animal products. Methods: Human mesenchymal cells were isolated from amniotic fluid samples (n = 12) obtained at 20 to 37 weeks' gestation. Their phenotypic profiles and cell proliferation rates were compared during expansion under 2 different media, containing either fetal bovine serum or allogeneic human AB serum. Statistical analyses were by the 2-sided Wilcoxon signed rank test and linear regression (P <.05). Results: Mesenchymal cells could be isolated and expanded at any gestational age. There was a greater than 9-fold logarithmic expansion of mesenchymal cells, with no significant differences in the overall proliferation rates based on serum type (P =.94), or gestational age (P =.14). At any passage, cells expanded for Lip to 50 days remained positive for markers consistent with a multipotent mesenchymal progenitor lineage, regardless of the medium used. Conclusions: Human mesenchymal amniocytes retain their progenitor phenotype and can be dependably expanded ex vivo in the absence of animal serum. Clinical trials of amniotic fluid-based tissue engineering are feasible within preferred regulatory guidelines. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Adv Fetal Care Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Ctr Human Cell Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Fauza, DO (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA 02115 USA. EM dario.fauza@childrens.harvard.edu FU NHLBI NIH HHS [U24 HL074355, U24 HL074355-01A1]; NIDDK NIH HHS [DK065406-02] NR 42 TC 56 Z9 58 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUN PY 2007 VL 42 IS 6 BP 974 EP 980 DI 10.1016/j.jpedsurg.2007.01.031 PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 182XC UT WOS:000247536300011 PM 17560205 ER PT J AU Lin, AE Silberbach, M AF Lin, Angela E. Silberbach, Michael TI Focus on the heart and aorta in Turner syndrome SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID GROWTH-HORMONE TREATMENT; MARFAN-SYNDROME; DISSECTION; DIMENSIONS; ANEURYSM; GIRLS C1 MassGen Hosp Children, Genet Unit, Boston, MA USA. Oregon Hlth & Sci Univ, Doernbecher Mem Hosp Children, Div Pediat Cardiol, Portland, OR 97201 USA. RP Lin, AE (reprint author), MassGen Hosp Children, Genet Unit, Boston, MA USA. EM silberbm@ohsu.edu NR 14 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2007 VL 150 IS 6 BP 572 EP 574 DI 10.1016/j.jpeds.2007.03.038 PG 3 WC Pediatrics SC Pediatrics GA 174KB UT WOS:000246939700004 PM 17517233 ER PT J AU Colombo, AV da Silva, CM Haffajee, A Colombo, APV AF Colombo, A. V. da Silva, C. M. Haffajee, A. Colombo, A. P. V. TI Identification of intracellular oral species within human crevicular epithelial cells from subjects with chronic periodontitis by fluorescence in situ hybridization SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE bacterial invasion; confocal microscopy; fluorescence in situ hybridization; gingival epithelial cells ID PORPHYROMONAS-GINGIVALIS INVASION; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; BUCCAL CELLS; BACTERIA; MICROORGANISMS; ASSOCIATION; PENETRATION; TREPONEMES; PATHOGENS; SURFACES AB Interactions between oral bacteria and gingival epithelial cells play an important role in the pathogenesis of periodontal diseases. This study used in situ hybridization with 16 rRNA probes and confocal microscopy to detect the periodontal pathogens Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Tannerella forsythia, and Treponema denticola within epithelial cells from periodontal pockets, gingival crevice, and buccal mucosa collected from subjects with chronic periodontitis (n = 14) and good periodontal health (n = 8). Each green fluorescent species-specific and universal probe was hybridized with all 58 epithelial samples from the 22 patients. The samples were observed by confocal microscopy to confirm the intracellular localization of oral species of bacteria. The mean frequency of detection and number of intracellular bacteria per epithelial cell were computed for each sample. The frequency of cells with internalized bacteria was higher in samples from the gingival crevice than in samples from the oral mucosa. Epithelial cells from all subjects harbored intracellular bacteria; however, patients with periodontitis presented significantly higher counts of bacteria per cell than periodontally healthy individuals (p < 0.05). Periodontal pathogens showed a trend to be detected in higher numbers in epithelial cells from periodontitis patients. In particular, T. forsythia and T. denticola were significantly more prevalent in periodontal pocket cells than healthy sulci and buccal cell samples in the periodontitis group (p < 0.05). Those findings indicate that crevicular and buccal cells present internalized bacteria, regardless of periodontal status. However, higher bacterial loads are detected in cells from subjects with periodontitis. C1 Univ Fed Rio de Janeiro, Inst Microbiol, Dept Med Microbiol, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Sch Dent, Dept Periodontol, Rio De Janeiro, Brazil. Forsyth Inst, Boston, MA USA. RP Colombo, APV (reprint author), R Gal Dionisio,60 Apt 604,Humaita, BR-22271050 Rio De Janeiro, Brazil. EM anapaulacolombo@yahoo.com RI Silva-Boghossian, Carina M./G-9440-2012 OI Silva-Boghossian, Carina M./0000-0002-4500-4350 NR 27 TC 50 Z9 52 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD JUN PY 2007 VL 42 IS 3 BP 236 EP 243 DI 10.1111/j.1600-0765.2006.00938.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 160LX UT WOS:000245943800006 PM 17451543 ER PT J AU Morasco, BJ Gfeller, JD Elder, KA AF Morasco, Benjamin J. Gfeller, Jeffrey D. Elder, Katherine A. TI The utility of the NEO-PI-R validity scales to detect response distortion: A comparison with the MMPI-2 SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID PERSONALITY-INVENTORY; SOCIAL DESIRABILITY; PSYCHOPATHOLOGY; METAANALYSIS; DISORDER; RATINGS; STYLE AB In this psychometric study, we compared the recently developed Validity Scales from the Revised NEO Personality Inventory (NEO PI-R; Costa & McCrae, 1992b) with the MMPI-2 (Butcher, Dahstrom, Graham, Tellegen, & Kaemmer, 1989) Validity Scales. We collected data from clients (n = 74) who completed comprehensive psychological evaluations at a university-based outpatient mental health clinic. Correlations between the Validity Scales of the NEO-PI-R and MMPI-2 were significant and in the expected directions. The relationships provide support for convergent and discriminant validity of the NEO-PI-R Validity Scales. The percent agreement of invalid responding on the two measures was high, although the diagnostic agreement was modest (kappa=.22-33). Finally, clients who responded in an invalid manner on the NEO-PI-R Validity Scales produced significantly different clinical profiles on the NEO-PI-R and MMPI-2 than clients with valid protocols. These results provide additional support for the clinical utility of the NEO-PI-R Validity Scales as indicators of response bias. C1 Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. St Louis Univ, Dept Psychiat, St Louis, MO 63103 USA. Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd P3MHDC, Portland, OR 97239 USA. EM benjamin.morasco@va.gov NR 37 TC 5 Z9 5 U1 2 U2 8 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD JUN PY 2007 VL 88 IS 3 BP 276 EP 283 PG 8 WC Psychology, Clinical; Psychology, Social SC Psychology GA 176XZ UT WOS:000247119500003 PM 17518549 ER PT J AU Simon, WA Herrmann, M Klein, T Shin, JM Huber, R Senn-Bilfinger, J Postius, S AF Simon, W. A. Herrmann, M. Klein, T. Shin, J. M. Huber, R. Senn-Bilfinger, J. Postius, S. TI Soraprazan: Setting new standards in inhibition of gastric acid secretion SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; PROTON PUMP INHIBITORS; K+-COMPETITIVE INHIBITOR; H,K-ATPASE; PANTOPRAZOLE; SCH-28080; MEMBRANES; BINDING; MUCOSA; ION AB After treatment of millions of patients suffering from gastroesophageal reflux disease (GERD) and other acid-related ailments with proton pump inhibitors, there are still unmet medical needs such as rapid and reliable pain relief, especially for nocturnal acid breakthrough. In this work, we introduce and characterize the biochemistry and pharmacology of the potassium-competitive acid blocker (P-CAB) soraprazan, a novel, reversible, and fast-acting inhibitor of gastric H,K-ATPase. Inhibitory and binding properties of soraprazan were analyzed together with its mode of action, its selectivity, and its in vivo potency. This P-CAB has an IC50 of 0.1 mu M if measured with ion leaky vesicles and of 0.19 mu M in isolated gastric glands. With a K-i of 6.4 nM, a K-d of 26.4 nM, and a B-max of 2.89 nmol/mg, this compound is a highly potent and reversible inhibitor of the H,K-ATPase. Soraprazan shows immediate inhibition of acid secretion in various in vitro models and in vivo and was found to be more than 2000-fold selective for H,K-ATPase over Na,K- and Ca-ATPases. Soraprazan is superior to esomeprazole in terms of onset of action and the extent and duration of pH elevation in vivo in the dog. Rapid and consistent inhibition of acid secretion by soraprazan renders the P-CABs a promising group of compounds for therapy of GERD. C1 ALTANA Pharma AG, Dept Biochem Gastroenterol, D-78467 Constance, Germany. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Herrmann, M (reprint author), ALTANA Pharma AG, Dept Biochem Gastroenterol, Ryk Gulden Str 2, D-78467 Constance, Germany. EM michael.herrmann@altanapharma.com NR 41 TC 33 Z9 35 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2007 VL 321 IS 3 BP 866 EP 874 DI 10.1124/jpet.107.120428 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 167LJ UT WOS:000246452900006 PM 17369284 ER PT J AU Rusch, D Musset, B Wulf, H Schuster, A Raines, DE AF Ruesch, Dirk Musset, Boris Wulf, Hinnerk Schuster, Anika Raines, Douglas E. TI Subunit-dependent modulation of the 5-hydroxytryptamine type 3 receptor open-close equilibrium by n-alcohols SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 14-18, 2006 CL Chicago, IL SP Amer Soc Anesthesiologists ID MEDIATED ION CURRENT; NICOTINIC ACETYLCHOLINE-RECEPTOR; NCB-20 NEUROBLASTOMA-CELLS; 5-HT3 RECEPTORS; ETHANOL POTENTIATION; RAT; ONDANSETRON; ANESTHETICS; EXPRESSION; NEURONS AB 5-Hydroxytryptamine (5-HT, serotonin) type 3 (5-HT3) receptors belong to the alcohol-sensitive superfamily of Cys-loop ligand-gated ion channels, and they are thought to play an important role in alcoholism. Alcohols with small molecular volumes increase the amplitude of currents evoked by low 5-HT concentrations and shift the 5-HT concentration-response curve for 5-HT3 receptor activation leftward, indicative of increased receptor sensitivity to agonist. This action is significantly smaller when currents are mediated by heteromeric 5-HT3AB receptors compared with homomeric 5-HT3A receptors. In this study, we used the highly inefficacious 5-HT3 receptor agonist dopamine to determine whether this difference between 5-HT3A and 5-HT3AB receptors reflects differential alcohol modulation of agonist binding affinity or channel gating efficacy. Human recombinant 5-HT3A and 5-HT3AB receptors were expressed in Xenopus oocytes, and currents were measured in the absence and presence of alcohols using the two-electrode voltage-clamp technique. Modulation by alcohols of peak currents elicited by maximally activating concentrations of dopamine was alcohol concentration-dependent. Potentiation by smaller alcohols was consistently significantly greater in 5-HT3A than in 5-HT3AB receptors, whereas inhibition by larger alcohols was not. A representative small ( butanol) and large ( octanol) alcohol failed to alter the EC50 value for channel activation by dopamine. We conclude that the presence of the 5-HT3B subunit in 5-HT3AB receptors significantly reduces the enhancement of gating efficacy by small alcohols without altering the inhibitory actions of large alcohols. C1 Univ Hosp Giessen Marburg GmbH, Dept Anesthesia & Crit Care, D-35033 Marburg, Germany. Univ Marburg, Div Neuroendocrinol & Neurodynam, Inst Physiol & Pathophysiol, Marburg, Germany. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Rusch, D (reprint author), Univ Hosp Giessen Marburg GmbH, Dept Anesthesia & Crit Care, Marburg Campus,Baldingerstr, D-35033 Marburg, Germany. EM ruesch@staff.uni-marburg.de RI Musset, Boris/J-2520-2013 OI Musset, Boris/0000-0001-8242-8817 FU NIGMS NIH HHS [P01-GM58448] NR 36 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2007 VL 321 IS 3 BP 1069 EP 1074 DI 10.1124/jpet.106.118752 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 167LJ UT WOS:000246452900029 PM 17360702 ER PT J AU Meredith, CW Jaffe, C Yanasak, E Cherrier, M Saxon, AJ AF Meredith, Charles W. Jaffe, Craig Yanasak, Elisia Cherrier, Monique Saxon, Andrew J. TI An open-label pilot study of risperidone in the treatment of methamphetamine dependence SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE amphetamine; methamphetamine; neuropsychology; risperidone; stimulant; treatment ID BRIEF SYMPTOM INVENTORY; DOPAMINE TRANSPORTER; ABSTINENT METHAMPHETAMINE; INDUCED REINSTATEMENT; COCAINE DEPENDENCE; STIMULANT ABUSE; D-AMPHETAMINE; DRUG-SEEKING; STRESS; TRIAL AB Psychopharmacological treatments for methamphetamine (MA) dependence have questionable efficacy. Open-label risperidone was evaluated in veterans seeking MA dependence treatment. Participants (N = 11) received four weeks of risperidone. They provided weekly self-reports of substance use, urine drug screens, and adverse effects. Neuropsychological assessments and psychiatric symptomatology (Brief Symptom Inventory; BSI) were measured at baseline and follow-up. The eight completers had an average risperidone dose of 3.6mg/day and decreased days of MA use during the trial from a mean of 13.0 (SD = 6.5) in the 30 days prior to starting risperidone to a mean of 0.125 (SD = 0.4; t = 5.7, p =.001). When measured over time, fine motor function (Grooved Peg Board Dominant Hand) was the only neuropsychological domain to improve significantly. No other domain changed significantly from baseline to follow-up among study completers. BSI data were converted to demographically corrected T-scores utilizing appropriate normative data (mean = 50, SD = 10). BSI somatization T-scores declined from a mean of 59.0 (SD = 8.4) to 51.8 (SD = 8.3; t = 2.7, p <.05), and positive symptom distress declined from a mean of 52.8 (SD = 8.0) to 41.7 (SD = 8.6; t = 3.0, p <.05), Risperidone was well tolerated and associated with decreased MA use. C1 VA Puget Sound Hlth Care Syst, Med Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Addict Psychiat Residency Program, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Addict Patient Care Line, Seattle, WA USA. RP Meredith, CW (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. EM cwmeredi@u.washington.edu NR 44 TC 17 Z9 19 U1 2 U2 4 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 USA SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JUN PY 2007 VL 39 IS 2 BP 167 EP 172 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 191OF UT WOS:000248140000007 PM 17703711 ER PT J AU Keuthen, NJ Flessner, CA Woods, DW Franklin, ME Stein, DJ Cashin, SE AF Keuthen, Nancy J. Flessner, Christopher A. Woods, Douglas W. Franklin, Martin E. Stein, Dan J. Cashin, Susan E. CA Trichotillomania Learning Ctr Sci TI Factor analysis of the Massachusetts General Hospital Hairpulling Scale SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE factor analysis; Hairpulling; self-report scale; trichotillomania ID BEHAVIORAL-THERAPY; TRICHOTILLOMANIA; IMPACT AB Objective: We explored the factor structure of the Massachusetts General Hospital Hairpulling Scale (MGH-HPS), a self-report measure for trichotillomania (TTM). Methods: Self-reported hairpullers who responded to an Internet-based survey (N=990) completed the MGH-HPS, demographic items, and other survey instruments. Principal axis exploratory factor analysis with Promax rotation of scores was conducted. Results: A two-factor solution was revealed, with "Severity" and "Resistance and Control" as separate factors. Conclusion: The MGH-HPS consists of two separate factors. Factor scores can be utilized to track naturalistic TTM symptom changes, improve patient characterization and treatment matching, and clarify the timing and mechanism of action for different treatment modalities. (C) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Trichotillomania Clin & Res Unit, Boston, MA 02114 USA. Univ Wisconsin, Milwaukee, WI 53201 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Cape Town, ZA-7925 Cape Town, South Africa. Mt Sinai Sch Med, New York, NY USA. RP Keuthen, NJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Trichotillomania Clin & Res Unit, Simches Res Bldg,Floor 2,185 Cambridge St, Boston, MA 02114 USA. EM nkeuthen@partners.org 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 9 TC 25 Z9 25 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUN PY 2007 VL 62 IS 6 BP 707 EP 709 DI 10.1016/j.jpsychores.2006.12.003 PG 3 WC Psychiatry SC Psychiatry GA 178PU UT WOS:000247233400014 PM 17540230 ER PT J AU Schumacher, HR Taylor, W Joseph-Ridge, N Perez-Ruiz, F Chen, LX Schlesinger, N Khanna, D Furst, DE Becker, MA Dalbeth, N Edwards, NL AF Schumacher, H. Ralph Taylor, William Joseph-Ridge, Nancy Perez-Ruiz, Fernando Chen, Lan X. Schlesinger, Naomi Khanna, Dinesh Furst, Daniel E. Becker, Michael A. Dalbeth, Nicola Edwards, N. Lawrence TI Outcome evaluations in gout SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 8th International Consensus Conference on Outcome Measures in Rheumatology Clinical Trails (OMERACT 8) CY MAY 10-14, 2006 CL St Julians Bay, MALTA DE gout; outcomes; OMERACT; uric acid ID RHEUMATOID-ARTHRITIS; CLINICAL-TRIALS; FACT TRIAL; ALLOPURINOL; FEBUXOSTAT; REDUCTION AB Methods to measure outcomes in gout still require consensus and validation. This Special Interest Group was assembled to identify domains of interest and is now evaluating a series of outcomes for features of acute gouty arthritis and chronic gout. To accomplish this, working groups have been formed and domains identified. Delphi methodology has been used to address gouty flares as an outcome of greatest interest. Studies addressing other outcome measures were reported at the OMERACT 8 meeting and validation has begun on some outcomes. There has been progress on developing a definition of a flare, and validating reproducibility of some chrome gout outcome measures in some domains, such as tophus size and patient perceptions. Use of these outcomes as well as a health-related quality of life measure are being studied in clinical trials. Pain on a Likert scale appears to be a valid outcome in acute gout. Final validation of these outcomes has not yet been achieved. In summary, the unique problems of evaluating outcomes in gout are finally being addressed. While no measures are available for use yet, an agenda has been developed. C1 VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Vet Affairs Med Ctr, Sch Med, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), VA Med Ctr, 151K,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu RI PEREZ-RUIZ, FERNANDO/E-4844-2012; OI Perez-Ruiz, Fernando/0000-0002-5268-1894 NR 17 TC 21 Z9 21 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 2007 VL 34 IS 6 BP 1381 EP 1385 PG 5 WC Rheumatology SC Rheumatology GA 176WW UT WOS:000247116600029 PM 17552064 ER PT J AU Baucom, B Eldridge, K Jones, J Sevier, M Clements, M Markman, H Stanley, S Sayers, SL Sher, T Christensen, A AF Baucom, Brian Eldridge, Kathleen Jones, Janice Sevier, Mia Clements, Mari Markman, Howard Stanley, Scott Sayers, Steven L. Sher, Tamara Christensen, Andrew TI Relative contributions of relationship distress and depression to communication patterns in couples SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY LA English DT Article ID MARITAL INTERACTION; SELF-REPORT; SEQUENTIAL INTERACTIONS; CONFLICT; WOMEN; BEHAVIOR; THERAPY; CONSISTENCY; ADJUSTMENT; OTHERS AB Researchers have long been interested in the relationship between marital distress and depression. Empirical findings from investigations into the relative contributions of marital distress and depression to marital communication have been inconsistent, and some communication behaviors, such as the demand/withdraw interaction pattern, have yet to be examined. The ability of depression to predict major types of communication (positive communication, negative communication, problem-solving, and demand/withdraw) was analyzed after controlling for the shared variance between marital distress and depression. Across two studies of couples beginning therapy and one study of couples beginning an enhancement program, results failed to provide support for a unique contribution of depression to couples' communication behaviors. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Denver, Denver, CO 80208 USA. Univ Penn, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. IIT, Chicago, IL 60616 USA. RP Baucom, B (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA. EM bbaucom@ucla.edu FU NICHD NIH HHS [R01 HD047564, R01 HD048780, R01 HD048780-02, R01 HD053314] NR 57 TC 6 Z9 6 U1 5 U2 8 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0736-7236 J9 J SOC CLIN PSYCHOL JI J. Soc. Clin. Psychol. PD JUN PY 2007 VL 26 IS 6 BP 689 EP 707 DI 10.1521/jscp.2007.26.6.689 PG 19 WC Psychology, Clinical; Psychology, Social SC Psychology GA 181AI UT WOS:000247408700003 PM 19343103 ER PT J AU Wehner, DT Ahlfors, SP Mody, M AF Wehner, Daniel T. Ahlfors, Seppo P. Mody, Maria TI The influence of semantic processing on phonological decisions-in children and adults: A magnetoencephalography (MEG) study SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE adults; children; magnetoencephalography; phonology; reading; semantics ID EVENT-RELATED POTENTIALS; INFERIOR PREFRONTAL CORTEX; LINGUISTICALLY DIVERSE LEARNERS; VISUAL WORD RECOGNITION; SURFACE-BASED ANALYSIS; MEDIAL TEMPORAL-LOBE; BRAIN POTENTIALS; CONTEXTUAL FACILITATION; FUNCTIONAL MRI; TIME-COURSE AB Purpose: To examine the behavioral effects and neural activation patterns associated with implicit semantic processing influences on phonological judgments during reading in children and adults. Method: Whole-head magnetoencephalography (MEG) recordings were obtained from 2 groups, children (9-13 years) and adults, performing a homophone judgment task. The stimuli consisted of pairs of sequentially presented written words that were either homophones, synonym foils, or unrelated control words. Results: The difference in the time taken to respond to synonym pairs relative to control pairs of stimuli, called the semantic interference effect (SIE), was, on average, 24 ms for adults and 86 ms for children. Source analysis of the MEG data using minimum-norm estimation (MNE) yielded less activation in the adults for the synonym condition compared with the control condition in right anterior temporal and inferior frontal cortex 300-500 ms after the onset of the 2nd word in a pair, suggestive of semantic priming as well as inhibition of the SIE. A similar priming effect was observed for the children in left-anterior temporal cortex. Conclusion: The observed group differences in the magnitude of the SIE and brain activation patterns may reflect developmental differences in the effects of semantic information on phonological decisions during word processing. C1 MIT, Massachusetts Gen Hosp, HMS, Athinoula A Martinos Ctr, Charlestown, MA USA. Harvard Univ, MIT, Div Hlth Sci & Technol Speech & Hearing Biosci, Cambridge, MA USA. Harvard Univ, MIT, Technol Program, Cambridge, MA USA. RP Mody, M (reprint author), MIT, Massachusetts Gen Hosp, HMS, Athinoula A Martinos Ctr, Charlestown, MA USA. EM mania@nmr.mgh.harvard.edu RI Ahlfors, Seppo/P-3644-2016 FU NCRR NIH HHS [P41RR14075]; NIDCD NIH HHS [DC-00159, DC00038] NR 98 TC 12 Z9 13 U1 3 U2 5 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD JUN PY 2007 VL 50 IS 3 BP 716 EP 731 DI 10.1044/1092-4388(2007/050) PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 177NM UT WOS:000247159800013 PM 17538111 ER PT J AU Heinzerling, KG Kral, AH Flynn, NM Anderson, RL Scott, A Gilbert, ML Asch, SM Bluthenthal, RN AF Heinzerling, Keith G. Kral, Alex H. Flynn, Neil M. Anderson, Rachel L. Scott, Andrea Gilbert, Mary L. Asch, Steven M. Bluthenthal, Ricky N. TI Human immunodeficiency virus and hepatitis C virus testing services at syringe exchange programs: Availability and outcomes SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE HIV testing; hepatitis C virus; syringe exchange programs; injection drug use ID INJECTION-DRUG USERS; HIV RISK; SEROCONVERSION; INFECTION; PREVALENCE; STRATEGIES; CLIENTS; CITIES; NEEDLE; COHORT AB We described the availability and outcomes of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) testing services at syringe exchange programs throughout California, using interviews with 24 syringe exchange Program directors and 560 syringe exchange clients. Both HIV and HCV testing services were available in 62% of programs, 21% had HIV testing only, and 17% had neither. Programs administered by health care/social service providers were more likely than independent syringe exchange programs to have HIV and HCV testing services available. Among clients of programs with testing available, clients of illegal programs were significantly less likely than clients of legal programs to have used syringe exchange HIN and HCV testing services. The availability of HIV and HCV testing services at syringe exchange programs varies, and the use of existing testing services by clients is not universal. Efforts to increase both the availability of HIV and HCV testing services at syringe exchange programs and the use of existing testing services are needed. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Integrated Subst Abuse Program, Los Angeles, CA 90095 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RTI Int, San Francisco, CA USA. Univ Calif San Francisco, Dept Family & Community Med, San Francisco, CA 94143 USA. Univ Calif Davis, Dept Internal Med, Div Infect Dis, Sacramento, CA 95817 USA. RAND Corp, Hlth Program, Santa Monica, CA USA. RAND Corp, Drug Policy Res Ctr, Santa Monica, CA USA. Calif State Univ Dominguez Hills, Urban Community Res Ctr, Dominiguez Hills, CA USA. RP Heinzerling, KG (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, 10880 Wilshire Blvd,Suite 540,Box 957087, Los Angeles, CA 90095 USA. EM heinzk@ucla.edu OI Bluthenthal, Ricky/0000-0003-3491-1702 FU NIDA NIH HHS [R01 DA14210]; PHS HHS [R06/CCR918667] NR 23 TC 4 Z9 4 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUN PY 2007 VL 32 IS 4 BP 423 EP 429 DI 10.1016/j.jsat.2006.11.002 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 169EP UT WOS:000246575800012 PM 17481466 ER PT J AU Khuri, SF Henderson, WG Daley, J Jonasson, O Jones, RS Campbell, DA Fink, AS Mentzer, RM Steeger, JE AF Khuri, Shukri F. Henderson, William G. Daley, Jennifer Jonasson, Olga Jones, R. Scott Campbell, Darrell A., Jr. Fink, Aaron S. Mentzer, Robert M., Jr. Steeger, Janet E. CA Principal Site Investigators TI The Patient Safety in Surgery Study: Background, study design, and patient populations SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID AFFAIRS SURGICAL RISK; QUALITY; CARE; ADJUSTMENT; PROGRAM AB Background: The purpose of this article is to describe the background, design, and patient populations of the Patient Safety in Surgery Study, as a preliminary to the articles in this journal that will report the results of the Study. Study Design: The Patient Safety in Surgery Study was a prospective cohort study. Trained nurses collected preoperative risk factors, operative variables, and 30-day postoperative mortality and morbidity outcomes in patients undergoing major general and vascular operations at 128 Veterans Affairs (VA) medical centers and 14 selected university medical centers between October 1, 2001 and September 30, 2004. An Internet-based data collection system was used to input data from the different private medical centers. Semiannual feedback of observed to expected mortality and morbidity ratios was provided to the participating medical centers. Results: During the 3-year study, total accrual in general surgery was 145,618 patients, including 68.5% from the VA and 31.5% from the private sector. Accrual in vascular surgery totaled 39,225 patients, including 77.8% from the VA and 22.2% from the private sector. VA patients were older and included a larger proportion of male patients and African Americans and Hispanics. The VA population included more inguinal, umbilical, and ventral hernia repairs, although the private-sector population included more thyroid and parathyroid, appendectomy, and operations for breast cancer. Preoperative comorbidities were similar in the two populations, but the rates of comorbidities were higher in the VA. American Society of Anesthesiologists classification tended to be higher in the VA. Conclusions: The National Surgical Quality Improvement Program methodology was successfully implemented in the 14 university medical centers. The data from the study provided the basis for the articles in this issue of the journal of the American College of Surgeons. C1 VA Boston Healthcare Syst, Surg Serv 112, West Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Tenet Healthcare Corp, Dallas, TX USA. Univ Illinois Hosp, Dept Surg, Chicago, IL USA. Amer Coll Surg, Chicago, IL USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Atlanta VA Med Ctr, Dept Surg, Decatur, GA USA. Emory Univ, Dept Surg, Atlanta, GA 30322 USA. Wayne State Univ, Sch Med, Detroit, MI USA. QCMetrix Inc, Waltham, MA USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM shukri.khuri@va.gov NR 25 TC 222 Z9 222 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1089 EP 1102 DI 10.1016/j.jamcollsurg.2007.03.028 PG 14 WC Surgery SC Surgery GA 177KT UT WOS:000247152700002 PM 17544068 ER PT J AU Henderson, WG Khuri, SF Mosca, C Fink, AS Hutter, MM Neumayer, LA AF Henderson, William G. Khuri, Shukri F. Mosca, Cecilia Fink, Aaron S. Hutter, Matthew M. Neumayer, Leigh A. TI Comparison of risk-adjusted 30-day postoperative mortality and morbidity in department of Veterans Affairs hospitals and selected university medical centers: General surgical operations in men SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; CARE; SURGERY; TRANSPLANTATION; SURVIVAL; VA AB Background: We used data from the Patient Safety in Surgery Study to compare patient populations, operative characteristics, and unadjusted and risk-adjusted 30-day postoperative mortality and morbidity between the Veterans Affairs (VA)(n=94,098) and private (n=18,399) sectors for general surgery operations in men. Study Design: This is a prospective cohort study. Trained nurses collected preoperative risk factors, operative variables, and 30-day postoperative mortality and morbidity outcomes in male patients undergoing major general surgery operations at 128 VA medical centers and 14 university medical centers from October 1, 2001, to September 30, 2004. Multiple logistic regression analysis was used to identify preoperative predictors of postoperative mortality and morbidity. An indicator variable for VA versus private-sector medical center was added to the model to determine if risk-adjusted outcomes were significantly different in the two systems. Results: The unadjusted 30-day mortality rate was higher in the VA compared with the private sector (2.62% versus 2.03%, p=0.0002); unadjusted morbidity rate was lower in the VA compared with the private sector (12.24% versus 13.99%, p<0.0001). After risk adjustment, odds ratio for mortality for the VA versus private sector was 1.23 (95% CI, 1.08-1.41). For morbidity after risk adjustment, the indicator variable for health-care system just missed statistical significance (p=0.0585). Thirty-day postoperative mortality was comparable in the VA and private sector for very common operations but was higher in the VA for less common, more complex operations. Conclusions: In general surgery operations in men, the VA appeared to have a higher risk-adjusted mortality rate compared with the private sector, but differences in mortality ascertainment in the two sectors might account for some of this effect. The higher mortality in the VA could be the result of higher mortality in the less common, more complex operations. There is a trend toward lower risk-adjusted morbidity in the VA compared with the private sector. C1 Vet Affairs Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. Atlanta VA Med Ctr, Dept Surg, Atlanta, GA USA. Emory Univ, Dept Surg, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. George E Whalen Salt Lake City VA Healthcare Syst, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. RP Henderson, WG (reprint author), Univ Colorado, Hlth Outcomes Program, MS F443-12477 E 19th Ave,POB 6508, Aurora, CO 80045 USA. EM william.henderson@uchsc.edu NR 20 TC 50 Z9 50 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1103 EP 1114 DI 10.1016/j.jamcollsurg.2007.02.068 PG 12 WC Surgery SC Surgery GA 177KT UT WOS:000247152700003 PM 17544069 ER PT J AU Hutter, MM Lancaster, RT Henderson, WG Khuri, SF Mosca, C Johnson, RG Abbott, WM Cambria, RP AF Hutter, Matthew M. Lancaster, Robert T. Henderson, William G. Khuri, Shukri F. Mosca, Cecilia Johnson, Robert G. Abbott, William M. Cambria, Richard P. TI Comparison of risk-adjusted 30-day postoperative mortality and morbidity in Department of Veterans Affairs hospitals and selected university medical centers: Vascular surgical operations in men SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; AORTIC-ANEURYSM REPAIR; CAROTID-ENDARTERECTOMY; CARE; OUTCOMES; SURGERY; VA; TRANSPLANTATION; SURVIVAL; BYPASS AB Background: In response to a Congressional mandate to compare risk-adjusted surgical outcomes from Department of Veterans Affairs (VA) hospitals with those from private-sector hospitals, the National Surgical Quality Improvement Program was initiated in the VA system and then was developed in a select group of university medical centers in the private sector. This article analyzes risk-adjusted outcomes after vascular surgical operations in men performed at VA hospitals as compared with private-sector hospitals. Study Design: This is a prospective cohort study of a sample of vascular surgical operations in men performed at 128 VA medical centers as compared with 14 university medical centers from October 1, 2001 to September 30, 2004. Patient and operative characteristics, and both unadjusted and risk-adjusted 30-day postoperative morbidity and mortality outcomes were compared. Results: Data from 30,058 vascular operations in men at VA hospitals were compared with 5,174 cases performed at private-sector hospitals. The unadjusted 30-day mortality rate was notably lower in the VA system as compared with the private-sector group (3.4% versus 4.2%, p=0.004). After risk-adjustment, there was no marked difference in mortality between the two hospital types. The unadjusted 30-day morbidity rate was also considerably lower in the VA hospitals as compared with the private sector (17.3% versus 22.3%, p<0.0001). After risk-adjustment, morbidity in the VA system remained considerably lower than in the private sector, with an odds ratio of 0.84 (95% CI, 0.78 to 0.92). Conclusions: In vascular surgical operations in men, the VA hospitals demonstrated a lower risk-adjusted 30-day morbidity rate than the private-sector group. There is no marked difference in adjusted mortality rates between the two types of institutions. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. St Louis Univ, Dept Surg, Div Cardiothorac Surg, St Louis, MO 63103 USA. John Cochran VA Med Ctr, St Louis, MO USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang ACC 335, Boston, MA 02114 USA. EM mhutter@partners.org NR 24 TC 31 Z9 31 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1115 EP 1126 DI 10.1016/j.jamcollsurg.2007.02.066 PG 12 WC Surgery SC Surgery GA 177KT UT WOS:000247152700004 PM 17544070 ER PT J AU Fink, AS Hutter, MM Campbell, DC Henderson, WG Mosca, C Khuri, SF AF Fink, Aaron S. Hutter, Matthew M. Campbell, Darrell C., Jr. Henderson, William G. Mosca, Cecilia Khuri, Shukri F. TI Comparison of risk-adjusted 30-day postoperative mortality and morbidity in Department of Veterans Affairs hospitals and selected university medical centers: General surgical operations in women SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY; CARE; SURGERY; TRANSPLANTATION; SURVIVAL; OUTCOMES; PROGRAM; BYPASS AB Background: In 1985, Congress mandated that the Department of Veterans Affairs (VA) compare its risk-adjusted surgical results with those in the private sector. The National Surgical Quality Improvement Program was developed as a result, in the VA system, and subsequently trialed in 14 university medical centers in the private sector. This report examines the results of the comparison between patient characteristics and outcomes of female general surgical patients in the two health care environments. Study Design: Preoperative patient characteristics and laboratory variables, operative variables, and unadjusted postoperative outcomes were compared between VA and the private sector populations. In addition, stepwise logistic regression models were developed for 30-day postoperative mortality and morbidity. Finally, the effect of being treated in a VA or private sector hospital was assessed by adding an indicator variable to the models and testing it for statistical significance. Results: Data from 5,157 female general surgical VA patients who underwent eligible procedures were compared with those from 27,467 patients in the private sector. Unadjusted 30-day mortality was virtually identical in the two groups (1.3%). The unadjusted morbidity rate was slightly, but notably, higher in the private sector (10.9%) as compared with that observed in the VA (8.5%, p<0.0001). Predictive models were generated for mortality and morbidity combining both groups; top variables in these models were similar to those described previously in the National Surgical Quality Improvement Program. The indicator variable for system of care (VA versus private sector) was not statistically significant in the mortality model, but substantially favored the VA in the morbidity model (odds ratio=0.80, 95% CI=0.71, 0.90). Conclusions: The data demonstrate that in female general surgical patients, risk-adjusted mortality rates are comparable in the VA and the private sector, but risk-adjusted morbidity is higher in the private sector. Rates of urinary tract infections in the two populations may account for much of the latter difference. C1 Vet Adm Med Ctr, Surg Serv 112, Atlanta, GA 30033 USA. Emory Univ, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Fink, AS (reprint author), Vet Adm Med Ctr, Surg Serv 112, 1670 Clairmont Rd, Atlanta, GA 30033 USA. NR 19 TC 35 Z9 35 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1127 EP 1136 DI 10.1016/j.jamcollsurg.2007.02.060 PG 10 WC Surgery SC Surgery GA 177KT UT WOS:000247152700005 PM 17544071 ER PT J AU Johnson, RG Wittgen, CM Hutter, MM Henderson, WG Mosca, C Khuri, SF AF Johnson, Robert G. Wittgen, Catherine M. Hutter, Matthew M. Henderson, William G. Mosca, Cecilia Khuri, Shukri F. TI Comparison of risk-adjusted 30-day postoperative mortality and morbidity in Department of Veterans Affairs hospitals and selected university medical centers: Vascular surgical operations in women SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; PERIPHERAL ARTERIAL-DISEASE; AORTIC-ANEURYSM REPAIR; SURGERY; CARE; OUTCOMES; MEN; VA AB Background: Women with peripheral vascular disease requiring vascular operations are less well studied than their male counterparts. The surgical outcomes of female vascular patients in the Department of Veterans Affairs (VA) and private sector hospitals have not previously been compared, and their preoperative risk profile, postoperative morbidity, and mortality need to be better elucidated. Study Design: Patients undergoing vascular operations at 14 private sector and 128 VA hospitals, from October 2001 through September 2004, had their preoperative characteristics, operative data, and 30-day postoperative morbidity and mortality compared, as part of the Patient Safety in Surgery (PSS) Study. Logistic regression analysis was performed to develop predictive models for morbidity and mortality, which allowed for a comparison of risk-adjusted outcomes between the two hospital groups. Results: There were 458 vascular surgical operations performed in women in the VA, and 3,535 vascular operations were performed in women in the private sector. Eighteen of 45 preoperative comorbidities and laboratory variables differed considerably between the institutions, and 16 of 18 were adverse among the private sector patients. The unadjusted 30-day mortality rate was higher in the private sector compared with the VA (5.2% versus 2.4%, p=0.008); the unadjusted morbidity rate was higher in the private sector compared with the VA sector (23.4% versus 13.3%, p<0.0001). After risk adjustment, there was no marked difference between the VA and the private sector in mortality (p=0.12), but the difference in morbidity rates remained pronounced, with an odds ratio of 0.60 for VA versus private sector (95% CI=0.44, 0.81). Conclusions: Compared with their VA counterparts, women undergoing vascular operations at private sector hospitals had a higher incidence of preoperative comorbidities; after risk adjustment, mortality did not differ substantially. Despite risk adjustment, the incidence of postoperative morbidity in the VA patients was considerably lower, suggesting unidentified differences in the hospital populations, their processes of care, or both. C1 St Louis Univ, Dept Surg, St Louis, MO 63110 USA. John Cochran VA Med Ctr, St Louis, MO USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Dept Vet Affairs, Univ Colorado Hlth Outcomes Program, Aurora, CO USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. VA Boston Healthcare Syst, Surg Serv, West Roxbury, MA USA. RP Johnson, RG (reprint author), St Louis Univ, Dept Surg, 3635 Vista & Grand Blvd, St Louis, MO 63110 USA. FU AHRQ HHS [5U18HS011913] NR 26 TC 21 Z9 21 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1137 EP 1146 DI 10.1016/j.jamcollsurg.2007.02.059 PG 10 WC Surgery SC Surgery GA 177KT UT WOS:000247152700006 PM 17544072 ER PT J AU Main, DS Cavender, TA Nowels, CT Henderson, WG Fink, AS Khuri, SF AF Main, Deborah S. Cavender, Tia A. Nowels, Carolyn T. Henderson, William G. Fink, Aaron S. Khuri, Shukri F. TI Relationship of processes and structures of care in general surgery to postoperative outcomes: A qualitative analysis SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID OF-VETERANS-AFFAIRS; SURGICAL CARE; HOSPITALS; COORDINATION; IMPROVEMENT; SERVICES; PROGRAM AB Background: With increased focus on improving surgical care quality, understanding structures and processes that influence surgical care is timely and important, as is more precise specification of these through improved measurement. Study Design: We conducted a qualitative study to help design a quantitative survey of structures and processes of surgical care. We audiotaped 44 face-to-face interviews with surgical care leaders and other diverse members of the surgical care team from 6 hospitals (two Veterans Affairs, four private sector). Qualitative interviews were transcribed and analyzed to identify common structures and processes mentioned by interviewees to include on a quantitative survey and to develop a rich description of salient themes on indicators of effective surgical care services and surgical care teams. Results: Qualitative analyses of transcripts resulted in detailed descriptions of structures and processes of surgical care services that affected surgical care team performance-and how particular structures led to effective and ineffective processes that impacted quality and outcomes of surgical care. Communication and care coordination were most frequently mentioned as essential to effective surgical care services and teams. Informants also described other influences on surgical quality and outcomes, such as staffing, the role of residents, and team composition and continuity. Conclusions: Surgical care team members reinforced the importance of understanding surgical care processes and structures to improve both quality and outcomes of surgical care. The analysis of interviews helped the study team identify potential measures of structures and processes to include in our quantitative survey. C1 UCDHSC, Colorado Hlth Outcomes Program, Aurora, CO 80045 USA. Metro Hlth Hosp, Grand Rapids, MI USA. Emory Univ, Atlanta Vet Affairs Med Ctr, Atlanta, GA 30322 USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Main, DS (reprint author), UCDHSC, Colorado Hlth Outcomes Program, Mail Stop F-443,POB 6508, Aurora, CO 80045 USA. EM debbi.main@uchsc.edu NR 23 TC 19 Z9 19 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1147 EP 1156 DI 10.1016/j.jamcollsurg.2007.03.013 PG 10 WC Surgery SC Surgery GA 177KT UT WOS:000247152700007 PM 17544073 ER PT J AU Main, DS Henderson, WG Pratte, K Cavender, TA Schiftner, TL Kinney, A Stoner, T Steiner, JF Fink, AS Khuri, SF AF Main, Deborah S. Henderson, William G. Pratte, Katherine Cavender, Tia A. Schiftner, Tracy L. Kinney, Anne Stoner, Tamara Steiner, John F. Fink, Aaron S. Khuri, Shukri F. TI Relationship of processes and structures of care in general surgery to postoperative outcomes: A descriptive analysis SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; OF-VETERANS-AFFAIRS; SURGICAL SERVICES; CLINICAL-OUTCOMES; HOSPITALS; COORDINATION; PATTERNS AB Background: The systematic collection of quantitative data on structures and processes from surgical services participating in the National Surgical Quality Improvement Program (NSQIP) has not been a focus to date. Efficient collection of useful measures of structures and processes may improve understanding of surgical outcomes and strategies for improving the quality of surgical care, as NSQIP continues to expand. The purpose of this article was to describe results of a quantitative survey designed to measure surgical care structures and processes within NSQIP sites. Study Design: A cross-sectional survey was mailed to 123 Department of Veteran Affairs (VA) and 14 private sector sites participating in the Agency for Healthcare Research and Quality (AHRQ)-funded Patient Safety in Surgery (PSS) Study. The survey included questions about organizational structures and processes of preoperative, intraoperative, and postoperative general surgical care services. For this study, we included only data from 90 VA sites that returned a survey (73% response rate). We used descriptive statistics and examined the bivariate association of structures and processes items or scales with risk-adjusted observed-to-expected (O/E) ratios of surgical morbidity and mortality. Results: Examination of frequency or means and standard deviations of items and scales revealed substantial variation in the structures and processes of surgical care services in participating VA sites, with correlation analyses demonstrating that, of 35 process and structure variables, there was a statistically significant relationship with the hospital's observed-to-expected ratio for 14 variables for morbidity, but only 4 variables for mortality. Conclusions: This descriptive analysis provides support for the potential importance of measuring organizational structures and processes of care in addition to risk-adjusted morbidity and mortality. C1 UCDHSC, Colorado Hlth Outcomes Program, Aurora, CO 80045 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Metro Hlth Hosp, Grand Rapids, MI USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. Emory Univ, Dept Surg, Atlanta Vet Affairs Med Ctr, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst,Dept Surg, Boston, MA USA. RP Main, DS (reprint author), UCDHSC, Colorado Hlth Outcomes Program, Mail Stop F-443,POB 6508, Aurora, CO 80045 USA. EM debbi.main@uchsc.edu NR 17 TC 23 Z9 23 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1157 EP 1165 DI 10.1016/j.jamcollsurg.2007.03.019 PG 9 WC Surgery SC Surgery GA 177KT UT WOS:000247152700008 PM 17544074 ER PT J AU Schifftner, TL Grunwald, GK Henderson, WG Main, D Khuri, SF AF Schifftner, Tracy L. Grunwald, Gary K. Henderson, William G. Main, Debbi Khuri, Shukri F. TI Relationship of processes and structures of care in general surgery to postoperative outcomes: A hierarchical analysis SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID LONG-TERM SURVIVAL; HOSPITAL CHARACTERISTICS; NONTEACHING HOSPITALS; VETERANS-AFFAIRS; RISK-ADJUSTMENT; SURGICAL SERVICES; MORTALITY-RATES; QUALITY; COMPLICATIONS; COORDINATION AB Background: The majority of studies relating processes and structures of surgical care to outcomes focus on mortality alone, even though morbidity outcomes are frequent, costly, and can have an adverse effect on a patient's short- and longterm survival and quality of life. The purpose of this study was to identify the important processes and structures of surgical care that relate to 30-day, risk-adjusted postoperative morbidity in general surgery. Study Design: Department of Veterans Affairs general surgery patients operated on in the period October 1, 2003 to September 30, 2004 at medical centers that participated in the Patient Safety in Surgery (PSS) Study and responded to a process anal structure of care survey were included in this study. The patient's risk information was combined with key process and structure variables in a hierarchical maximum likelihood analysis to predict 30-day postoperative morbidity. Results: A number of hospital-level processes and structures of care were identified that predicted 30-day postoperative morbidity. The dominant factor was university affiliation. Affiliated hospitals showed an increase in risk of morbidity even after adjustment for patient risk. Conclusions: Risk-adjusted morbidity is higher in Veterans Affairs hospitals that are affiliated with university medical centers. These findings mandate additional study to identify the exact factors responsible for this increased morbidity. C1 Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. Univ Colorado, Denver Hlth Sci Ctr, Aurora, CO USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Schifftner, TL (reprint author), VA Natl Surg Qual Improvement Program, POB 6508,Mail Stop F-443, Aurora, CO 80045 USA. NR 29 TC 16 Z9 16 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1166 EP 1177 DI 10.1016/j.jamcollsurg.2007.03.023 PG 12 WC Surgery SC Surgery GA 177KT UT WOS:000247152700009 PM 17544075 ER PT J AU Neumayer, L Hosokawa, P Itani, K El-Tamer, M Henderson, WG Khuri, SF AF Neumayer, Leigh Hosokawa, Patrick Itani, Kamal El-Tamer, Mahmoud Henderson, William G. Khuri, Shukri F. TI Multivariable predictors of postoperative surgical site infection after general and vascular surgery: Results from the Patient Safety in Surgery Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID RISK ADJUSTMENT; QUALITY; CARE AB Background: Surgical site infection (SSI) is a potentially preventable complication. We developed and tested a model to predict patients at high risk for surgical site infection. Study Design: Data from the Patient Safety in Surgery Study/National Surgical Quality Improvement Program from a 3-year period were used to develop and test a predictive model of SSI using logistic regression analyses. Results: From October 2001 through September 2004, 7,035 of 163,624 (4.30%) patients undergoing vascular and general surgical procedures at 14 academic and 128 Department of Veterans Affairs (VA) medical centers experienced SSI. Fourteen variables independently associated with increased risk of SSI included patient factors (age greater than 40 years, diabetes, dyspnea, use of steroids, alcoholism, smoking, recent radiotherapy, and American Society of Anesthesiologists class 2 or higher), preoperative laboratory values (albumin <3.5 mg/dL, total bilirubin >1.0 mg/dL), and operative characteristics (emergency, complexity [work relative value units >= 10], type of procedure, and wound classification). The SSI risk score is more accurate than the National Nosocomial Infection Surveillance score in predicting SSI (c-indices 0.70, 0.62, respectively). Conclusions: We developed and tested an accurate prediction score for SSI. Clinicians can use this score to predict their patient's risk of an SSI and implement appropriate prevention strategies. C1 Univ Utah, Dept Surg, Salt Lake City, UT 84132 USA. George E Whalen Salt Lake City VA Hlth Care Syst, Dept Surg, Salt Lake City, UT USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Boston VA Healthcare Syst, West Roxbury, MA USA. Boston Univ, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Columbia Univ, Dept Surg, New York Presbyterian Hosp, New York, NY USA. RP Neumayer, L (reprint author), Univ Utah, Dept Surg, 50 N Med Dr, Salt Lake City, UT 84132 USA. NR 8 TC 157 Z9 160 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1178 EP 1187 DI 10.1016/j.jamcollsurg.2007.03.022 PG 10 WC Surgery SC Surgery GA 177KT UT WOS:000247152700010 PM 17544076 ER PT J AU Johnson, RG Arozullah, AM Neumayer, L Henderson, WG Hosokawa, P Khuri, SF AF Johnson, Robert G. Arozullah, Ahsan M. Neumayer, Leigh Henderson, William G. Hosokawa, Patrick Khuri, Shukri F. TI Multivariable predictors of postoperative respiratory failure after general and vascular surgery: Results from the Patient Safety in Surgery Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID MULTIFACTORIAL RISK INDEX; AFFAIRS SURGICAL RISK; COLLEGE-OF-PHYSICIANS; NONCARDIOTHORACIC SURGERY; PULMONARY COMPLICATIONS; QUALITY; ADJUSTMENT; CARE; DETERMINANTS; BYPASS AB Background: Postoperative respiratory failure (RF) is associated with an increase in hospital morbidity, mortality, cost, and late mortality. We developed and tested a model to predict the risk of postoperative RF in patients undergoing major vascular and general surgical operations. This model is an extension of an earlier model that was derived and tested exclusively from a population of male patients from the Veterans Affairs National Surgical Quality Improvement Program. Methods: Patients undergoing vascular and general surgical procedures at 14 academic and 128 Veterans Affairs Medical Centers from October 2001 through September 2004 were used to develop and test a predictive model of postoperative RF using logistic regression analyses. RF was defined as postoperative mechanical ventilation for longer than 48 hours or unanticipated reintubation. Results: Of 180,359 patients, 5,389 (3.0%) experienced postoperative RE Twenty-eight variables were found to be independently associated with RE Current procedural terminology group, patients with a higher American Society of Anesthesiologists classification, emergency operations, more complex operation (work relative value units), preoperative sepsis, and elevated creatinine were more likely to experience RE Older patients, male patients, smokers, and those with a history of congestive heart failure or COPD, or both, were also predisposed. The model's discrimination (c-statistic) was excellent, with no decrement from development (0.856) to validation (0.863) samples. Conclusions: This model updates a previously validated one and is more broadly applicable. Its use to predict postoperative RF risk enables the study of preventative measures or preoperative risk adjustment and intervention to improve outcomes. C1 St Louis Univ, Dept Surg, St Louis, MO 63110 USA. John Cochran VA Med Ctr, St Louis, MO USA. Univ Illinois, Gen Internal Med Sect, Chicago, IL USA. Jesse Brown VA Med Ctr, Chicago, IL USA. George E Whalen Salt Lake City VA Healthcare Syst, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. Dept Vet Affairs, Univ Colorado Hlth Outcomes Program, Aurora, CO USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Johnson, RG (reprint author), St Louis Univ, Dept Surg, 3635 Vista & Grand Blvd, St Louis, MO 63110 USA. EM johnsorg@slu.edu NR 16 TC 117 Z9 120 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1188 EP 1198 DI 10.1016/j.jamcollsurg.2007.02.070 PG 11 WC Surgery SC Surgery GA 177KT UT WOS:000247152700011 PM 17544077 ER PT J AU Rogers, SO Kilaru, RK Hosokawa, P Henderson, WG Zinner, MJ Khuri, SF AF Rogers, Selwyn O., Jr. Kilaru, Ravi K. Hosokawa, Patrick Henderson, William G. Zinner, Michael J. Khuri, Shukri F. TI Multivariable predictors of postoperative venous thromboembolic events after general and vascular surgery: Results from the Patient Safety in Surgery Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID MULTIFACTORIAL RISK INDEX; AFFAIRS SURGICAL RISK; HOSPITALIZED-PATIENTS; PULMONARY-EMBOLISM; ADJUSTMENT; THROMBOSIS; MORTALITY; QUALITY; CARE; PREVENTION AB Background: Venous thromboembolism (VTE) is a potentially preventable postoperative complication. Accurate risk prediction is an essential first step toward limiting serious, and sometimes fatal, postoperative VTE. We sought to develop and test a model to predict patients at high risk for postoperative VTE. Study Design: Data from the Patient Safety in Surgery (PSS) Study were used to develop and test a predictive model of VTE using multiple logistic regression analyses. Results: VTE occurred in 1,162 of 183,069 (0.63%) patients undergoing vascular and general surgical procedures. The 30-day mortality in patients who suffered a VTE was 11.19%. Fifteen variables independently associated with increased risk of VTE included patient factors (female gender, higher American Society of Anesthesiologists class, ventilator dependence, preoperative dyspnea, disseminated cancer, chemotherapy within 30 days, and >4 U packed red blood cell transfusion in the 72 hours before operation), preoperative laboratory values (albumin <3.5 mg/dL, bilirubin >1.0 mg/dL, sodium >145 mmol/L, and hematocrit <38%), and operative characteristics (type of surgical procedure, emergency operation, work relative value units, and infected/contaminated wounds). These variables were used to develop a predictive model for postoperative VTE (c-index=0.7647) and a risk score that can be used in the preoperative assessment of patients undergoing major operations. Conclusions: Venous thromboembolic events after noncardiac operations are relatively infrequent but highly lethal. Important multivariable risk factors for VTE in this setting were identified in the large PSS database. The risk-prediction scoring system, developed by using the logistic regression odds ratios, helps to identify patients at risk for postoperative VTE and to institute appropriate perioperative prophylactic measures. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. Danbury Hosp, Div Cardiol, Danbury, CT USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. Univ Colorado Hlth Outcomes Program, Aurora, CO USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rogers, SO (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM srogers@partners.org NR 24 TC 83 Z9 86 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1211 EP 1221 DI 10.1016/j.jamcollsurg.2007.02.072 PG 11 WC Surgery SC Surgery GA 177KT UT WOS:000247152700013 PM 17544079 ER PT J AU Hall, BL Hirbe, M Yan, Y Khuri, SF Henderson, WG Hamilton, BH AF Hall, Bruce Lee Hirbe, Mitzi Yan, Yan Khuri, Shukri F. Henderson, William G. Hamilton, Barton H. TI Thyroid and parathyroid operations in Veterans Affairs and selected university medical centers: Results of the Patient Safety in Surgery Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID LOCAL-ANESTHESIA; RISK ADJUSTMENT; SURGICAL CARE; GENERAL-ANESTHESIA; NECK EXPLORATION; QUALITY AB Background: There is increasing interest in surgical outcomes. The Patient Safety in Surgery (PSS) Study database was examined about thyroid and parathyroid procedures to determine risk factors for adverse outcomes and outcomes rates. Relative outcomes performance for the Veterans Affairs (VA) and private-sector populations was compared after risk adjustment. Study Design: Preoperative, operative, and postoperative data were analyzed for 7,082 patients: 2,814 VA patients and 4,268 private sector patients. Prevalence of risk or process factors was described. Occurrence rates and unadjusted odds ratios (OR) for adverse outcomes were calculated. Stepwise multiple logistic regressions were performed to model the impact of various factors on outcomes and to calculate the adjusted OR for any adverse event for the VA population compared with the private sector. Results: Overall mortality rate was 0.35% and 0.60% in the VA and 0.19% in the private sector. Overall rate of any adverse outcomes was 2.90% and 4.48% in the VA and 1.97% in the private sector. Adjusted OR for thyroid versus parathyroid operation was 0.94 (95% CI, 0.67-1.31). Adjusted OR for operation in the VA versus private sector was 1.25 (95% CI, 0.87-1.78). Conclusions: Overall rates of mortality and any morbidity were low and consistent with previous reports. Based on adjusted OR, there was no significant difference in outcomes for thyroid versus parathyroid operation. Similarly, there was no apparent significant difference in surgical outcomes between the VA and private-sector groups after risk adjustment. C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, John M Olin Sch Business, St Louis, MO 63130 USA. Washington Univ, Ctr Hlth Policy, St Louis, MO 63130 USA. Washington Univ, Dept Surg, Div Urol Surg, St Louis, MO 63130 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Colorado Hlth Outcomes Program, Aurora, CO USA. RP Hall, BL (reprint author), Washington Univ, Sch Med, Dept Surg, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. EM hallb@wustl.edu RI Hamilton, Barton/P-5187-2015 NR 18 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1222 EP 1234 DI 10.1016/j.jamcollsurg.2007.02.073 PG 13 WC Surgery SC Surgery GA 177KT UT WOS:000247152700014 PM 17544080 ER PT J AU Neumayer, L Schifftner, TL Henderson, WG Khuri, SF El-Tamer, M AF Neumayer, Leigh Schifftner, Tracy L. Henderson, William G. Khuri, Shukri F. El-Tamer, Mahmoud TI Breast cancer surgery in Veterans Affairs and selected university medical centers: Results of the Patient Safety in Surgery Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID RISK ADJUSTMENT; SURGICAL CARE; QUALITY; MORBIDITY AB Background: Breast cancer is a common diagnosis. We compare perioperative characteristics and outcomes between male and female patients undergoing treatment for breast cancer and between hospital systems (Department of Veterans Affairs [VA] and private sector [PS]) as part of the Patient Safety in Surgery (PSS) Study. Study Design: We performed an analysis of a prospectively collected clinical database. Data collected from 128 VA hospitals and 14 PS academic medical centers as part of the Patient Safety in Surgery Study for fiscal years 2002 through 2004 were used. Analysis included calculation of crude and adjusted odds ratios for morbidity. Results: A total of 3,823 patients were included. Female VA patients at baseline had higher rates of smoking, steroid use, COPD, acute renal failure, dialysis, weight loss >10%, preoperative chemotherapy, and abnormal laboratory values than female PS patients did. Male patients were older than the female patients in both hospital systems. Mortality rates were very low and similar among groups. All VA patients in this study had substantially longer lengths of stay than the patients in the PS. The unadjusted overall complication rate was 5.21%; the VA female patients experienced an unadjusted complication rate twice that of the PS female patients. When adjusted for confounding variables and differences in preoperative comorbidities, the odds ratio comparing VA with PS females was no longer markedly different (1.404; 95% CI, 0.894, 2.204). Conclusions: VA patients with breast cancer have higher incidences of most comorbidities than patients in the PS. Differences in complication rates females disappear when adjustment is made for the higher rates of comorbidities in the VA patients. C1 George E Whalen Salt Lake City VA Hlth Care Syst, Dept Surg, Salt Lake City, UT 84132 USA. Univ Utah, Salt Lake City, UT 84132 USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. Univ Colorado Hlth Outcomes Program, Aurora, CO USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Columbia Univ, New York Presbyterian Hosp, New York, NY USA. RP Neumayer, L (reprint author), George E Whalen Salt Lake City VA Hlth Care Syst, Dept Surg, 50 N Med Dr, Salt Lake City, UT 84132 USA. NR 6 TC 30 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1235 EP 1241 DI 10.1016/j.jamcollsurg.2007.03.018 PG 7 WC Surgery SC Surgery GA 177KT UT WOS:000247152700015 PM 17544081 ER PT J AU Lancaster, RT Tanabe, KK Schifftner, TL Warshaw, AL Henderson, WG Khuri, SF Hutter, MM AF Lancaster, Robert T. Tanabe, Kenneth K. Schifftner, Tracy L. Warshaw, Andrew L. Henderson, William G. Khuri, Shukri F. Hutter, Matthew M. TI Liver resection in Veterans Affairs and selected university medical centers: Results of the Patient Safety in Surgery Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID SURGICAL CARE; RISK ADJUSTMENT; QUALITY; PROGRAM AB Background: A congressional mandate, which led to the formation of the National Surgical Quality Improvement Program, is now being fulfilled with the publication of general and vascular surgical outcomes comparisons between Veterans Affairs (VA) and university medical centers. A series of National Surgical Quality Improvement Program articles evaluate the effect of hospital type (VA versus university hospitals) on procedure-specific outcomes. This article focuses on liver resections. Study Design: This is a prospective cohort study of a sample of patients undergoing liver resections at 128 VA medical centers compared with 14 university medical centers from October 1, 2001, to September 30, 2004. Preoperative and intraoperative characteristics were evaluated to identify possible variables related to morbidity and mortality and possible confounders of the hospital effect. These variables were then used to identify the effect that the hospital setting might have on surgical outcomes after liver resections. Results: Data from 237 liver resections at VA hospitals were compared with 783 procedures performed at university hospitals. The unadjusted 30-day morbidity rate tended to be higher in the VA (university 22.6% versus VA 27.9%; p=0.10). After risk adjustment, results were equivalent (odds ratio=0.94; p=0.77). Unadjusted 30-day mortality rate was significantly higher in VA hospitals (6.8% versus 2.6%; p=0.002). After risk adjustment, there was no longer a significant difference in mortality between the two hospital systems (odds ratio=1.62; p=0.33). Conclusions: For liver resections, the National Surgical Quality Improvement Program and Patient Safety in Surgery Study data suggest that there is no significant difference in risk-adjusted morbidity or mortality rates between VA and the university medical centers. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. Dept Vet Affairs, Natl Surg Qual Improvement Program Off Patient Ca, Aurora, CO USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang ACC 460, Boston, MA 02114 USA. EM mhutter@partners.org NR 19 TC 11 Z9 11 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1242 EP 1251 DI 10.1016/j.jamcollsurg.2007.02.069 PG 10 WC Surgery SC Surgery GA 177KT UT WOS:000247152700016 PM 17544082 ER PT J AU Glasgow, RE Jackson, HH Neumayer, L Schifftner, TL Khuri, SF Henderson, WG Mulvihill, SJ AF Glasgow, Robert E. Jackson, Heidi H. Neumayer, Leigh Schifftner, Tracy L. Khuri, Shukri F. Henderson, William G. Mulvihill, Sean J. TI Pancreatic resection in Veterans Affairs and selected university medical centers: Results of the Patient Safety in Surgery Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID EXTENDED RETROPERITONEAL LYMPHADENECTOMY; HOSPITAL VOLUME; OPERATIVE MORTALITY; UNITED-STATES; CONSECUTIVE PANCREATICODUODENECTOMIES; PERIAMPULLARY ADENOCARCINOMA; CONTROLLED TRIAL; SURGICAL CARE; CANCER; RISK AB Background: Pancreatectomy is a high-risk, technically demanding operation associated with substantial perioperative morbidity and mortality. This study aims to describe the 30-day morbidity and mortality for pancreatectomy and to compare outcomes between private-sector and Veterans Affairs hospitals using multiinstitutional data. Study Design: This is a retrospective review of patients who underwent pancreatic resection for neoplasia at private-sector (PS) and Veterans Affairs (VA) hospitals participating in the National Surgical Quality Improvement Program Patient Safety in Surgery Study in fiscal years 2002 to 2004. The variables reviewed were demographics, preoperative medical conditions, intraoperative variables, and outcomes. Using logistic regression to control for differences in patient comorbidities, 30-day mortality and morbidity rates between PS and VA hospitals were compared. Results: A total of 1,069 patients underwent pancreatectomy for neoplasia at 97 participating hospitals. Six hundred ninety-two patients were treated at PS hospitals and 377 at VA hospitals. The average number of patients treated at each hospital was 11.0, with a range of 1 to 83 during the 3-year study period. There were 842 patients who underwent pancreaticoduodenectomy (CPT 4815x) and 227 who underwent distal/subtotal pancreatectomy (CPT 4814x). Significant differences were observed between PS patients and VA patients with regard to comorbidities and patient demographics. The 30-day unadjusted morbidity rate was 33.8% overall, 42.2% at VA hospitals versus 29.1% at PS hospitals (p<0.0001). Unadjusted and adjusted odds ratio (OR) for postoperative morbidity comparing VA with PS hospitals was 1.781 (95% CI, 1.369-2.318) and 1.581 (95% CI, 1.064-2.307). The 30-day unadjusted operative mortality rate was 3.8% overall, 6.4% at VA hospitals and 2.5% at PS hospitals (p=0.0015). Unadjusted and adjusted OR for postoperative mortality was 2.909 (95% CI, 1.525-5.549) and 2.533 (95% CI, 1.020-6.290), respectively. Similar outcomes were observed when looking at pancreaticoduodenectomy (CPT 4815x) when analyzed independent of other types of pancreatic resections. Conclusion: Pancreatectomies are high-risk operations with substantial perioperative morbidity and mortality. Risk-adjusted outcomes for patients treated at PS hospitals were found to be superior to those for patients treated at VA hospitals in the study. C1 Univ Utah, Dept Surg, Salt Lake City, UT 84112 USA. George E Whalen Salt Lake City VA Hlth Care Syst, Salt Lake City, UT USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Colorado Hlth Outcomes Program, Aurora, CO USA. RP Glasgow, RE (reprint author), Univ Utah, Dept Surg, 30 North,1900 East, Salt Lake City, UT 84112 USA. EM robert.glasgow@hsc.utah.edu NR 30 TC 41 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1252 EP 1260 DI 10.1016/j.jamcollsurg.2007.03.015 PG 9 WC Surgery SC Surgery GA 177KT UT WOS:000247152700017 PM 17544083 ER PT J AU Turrentine, FE Henderson, WG Khuri, SF Schifftner, TL Inabnet, WB El-Tamer, M Northup, CJ Simpson, VB Neumayer, L Hanks, JB AF Turrentine, Florence E. Henderson, William G. Khuri, Shukri F. Schifftner, Tracy L. Inabnet, William B., III El-Tamer, Mahmoud Northup, C. Joseph Simpson, Virginia B. Neumayer, Leigh Hanks, John B. TI Adrenalectomy in Veterans Affairs and selected university medical centers: Results of the Patient Safety in Surgery Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; PRIVATE-SECTOR HOSPITALS; SURGICAL CARE; LAPAROSCOPIC ADRENALECTOMY; RISK ADJUSTMENT; UNITED-STATES; POSTOPERATIVE MORTALITY; VOLUME; EXPERIENCE; VA AB Background: Data from the Patient Safety in Surgery Study were used to compare preoperative risk factors, intraoperative variables, and surgical outcomes of adrenalectomy procedures performed in 81 Veterans Affairs (VA) hospitals with those performed in 14 private-sector (PS) hospitals. Study Design: This study is a retrospective review of prospectively collected data on all patients undergoing adrenalectomy in the VA and PS for fiscal years 2002 through 2004. Bivariate analysis compared VA and PS preoperative risk factors, intraoperative variables, and 30-day morbidity and mortality. Regression risk-adjustment analysis was used to compare 30-day postoperative morbidity in the VA and PS. Results: During the 3 years studied, 178 VA patients and 371 PS patients underwent adrenalectomy procedures with a median per site of 2 (range 1-9) and 21 (range 8-70) procedures per VA and PS hospital, respectively. The VA patients had considerably more comorbidities than PS patients. The unadjusted 30-day morbidity rate was significantly higher in VA (16.29%) than PS (6.74%) hospitals (p=0.0003); after controlling for the higher rate of comorbidities, the adjusted odds ratio for morbidity in the VA versus the PS hospitals was no longer significant (odds ratio=1.328; 95% CI, 0.488-3.613). Unadjusted mortality rate was VA 2.81%, PS 0.27%, p=0.0074. The low event rate overall precluded risk adjustment for mortality. Conclusions: The VA adrenalectomy population has more preoperative risk factors and substantially higher unadjusted 30-day postoperative morbidity and mortality rates than the PS population. After risk adjustment, there is no significant difference in morbidity between the VA and the PS. A larger study population is needed to compare risk-adjusted mortality between the VA and PS. C1 Univ Virginia, Dept Surg, Charlottesville, VA 22908 USA. Univ Colorado Hlth Outcomes Program, Aurora, CO USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dept Vet Affairs, Natl Surg Qual Improvement Program, Off Patient Care Serv, Aurora, CO USA. Columbia Univ, New York Presbyterian Hosp, New York, NY USA. George E Wahlen Salt Lake City VA Hlth Care Syst, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. RP Hanks, JB (reprint author), Univ Virginia, Dept Surg, POB 800709, Charlottesville, VA 22908 USA. EM jbh@virginia.edu RI Turrentine, Florence/F-6937-2015 OI Turrentine, Florence/0000-0002-0313-2813 NR 33 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1273 EP 1283 DI 10.1016/j.jamcollsurg.2007.03.014 PG 11 WC Surgery SC Surgery GA 177KT UT WOS:000247152700019 PM 17544085 ER PT J AU Virani, S Michaelson, JS Hutter, MM Lancaster, RT Warshaw, AL Henderson, WG Khuri, SF Tanabe, KK AF Virani, Sophia Michaelson, James S. Hutter, Matthew M. Lancaster, Robert T. Warshaw, Andrew L. Henderson, William G. Khuri, Shukri F. Tanabe, Kenneth K. TI Morbidity and mortality after liver resection: Results of the Patient Safety in Surgery Study SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID AFFAIRS SURGICAL RISK; HEPATOCELLULAR-CARCINOMA; HEPATIC RESECTION; HEPATECTOMY; ADJUSTMENT; DATABASE; OUTCOMES; QUALITY; CARE AB Background: Liver resection is performed with increasing frequency. Nearly all of the published information on operative mortality and morbidity rates associated with liver resection is derived from studies that rely on retrospective data collection from single centers. The goal of this study is to use audited multiinstitutional data from the private sector of the Patient Safety in Surgery Study to characterize complications after liver resection and to identify variables that are associated with 30-day morbidity and mortality. Study Design: Prospectively collected data on liver resection patients from 14 hospitals were collected using National Surgical Quality Improvement Program's methodology. Rates of occurrence of 21 defined postoperative complications were measured. Bivariate analyses and stepwise logistic regression were used to identify factors associated with 30-day morbidity and mortality. Results: At least one complication occurred in 22.6% of patients within 30 days. Stepwise logistic regression identified several preoperative factors associated with morbidity, including serum albumin, SGOT >40, previous cardiac operation, operative work relative value unit, and history of severe COPD. Mortality within 30 days was observed in 2.6% of patients. Factors associated with mortality were found to be male gender, American Society of Anesthesiologists class 3 or higher, presence of ascites, dyspnea, and severe COPD. Only 0.7% of patients without any complications died, compared with 9.0% of patients with at least 1 complication (p<0.0001). Conclusions: Prospective, standardized, audited, multiinstitutional data were analyzed to identify several preoperative and intraoperative factors associated with morbidity and mortality after liver resection. These factors should be considered during patient selection and perioperative management. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Colorado Hlth Outcomes Program, Aurora, CO USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Dept Surg, Yawkey 7-924,55 Fruit St, Boston, MA 02114 USA. NR 13 TC 95 Z9 100 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1284 EP 1292 DI 10.1016/j.jamcollsurg.2007.02.067 PG 9 WC Surgery SC Surgery GA 177KT UT WOS:000247152700020 PM 17544086 ER PT J AU Rowell, KS Turrentine, FE Hutter, MM Khuri, SF Henderson, WG AF Rowell, Katherine S. Turrentine, Florence E. Hutter, Matthew M. Khuri, Shukri F. Henderson, William G. TI Use of National Surgical Quality Improvement Program data as a catalyst for quality improvement SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID OF-VETERANS-AFFAIRS; RISK ADJUSTMENT; CARE; CATHETER; OUTCOMES; INFECTIONS; MORTALITY; TRIAL; COMPLICATIONS; MORBIDITY AB Background: Semiannually, the National Surgical Quality Improvement Program (NSQIP) provides its participating sites with observed-to-expected (O/E) ratios for 30-day postoperative mortality and morbidity At each reporting period, there is typically a small group of hospitals with statistically significantly high O/E ratios, meaning that their patients have experienced more adverse events than would be expected on the basis of the population characteristics. An important issue is to determine which actions a surgical service should take in the presence of a high O/E ratio. Study Design: This article reviews case studies of how some of the Department of Veterans Affairs and private-sector NSQIP participating sites used the clinically rich NSQIP database for local quality improvement efforts. Data on postoperative adverse events before and after these local quality improvement efforts are presented. Results: After local quality improvement efforts, wound complication rates were reduced at the Salt Lake City Veterans Affairs medical center by 47%, surgical site infections in patients undergoing intraabdominal surgery were reduced at the University of Virginia by 36%, and urinary tract infections in vascular patients were reduced at the Massachusetts General Hospital by 74%. At some sites participating in the NSQIP, notably the Massachusetts General Hospital and the University of Virginia, the NSQIP has served as the basis for surgical service-wide outcomes research and quality improvement programs. Conclusions: The NSQIP not only provides participating sites with risk-adjusted surgical mortality and morbidity outcomes semiannually, but the clinically rich NSQIP database can also serve as a catalyst for local quality improvement programs to significantly reduce postoperative adverse event rates. C1 QCMetrix Inc, Waltham, MA 02451 USA. Univ Virginia, Dept Surg, Charlottesville, VA USA. Massachusetts Gen Hosp, Dept Surg, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. VA Boston Healthcare Syst, West Roxbury, MA USA. Univ Colorado Hlth Outcomes Program, Aurora, CO USA. RP Rowell, KS (reprint author), QCMetrix Inc, 400-1 Totten Pond Rd, Waltham, MA 02451 USA. RI Turrentine, Florence/F-6937-2015 OI Turrentine, Florence/0000-0002-0313-2813 NR 24 TC 125 Z9 125 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2007 VL 204 IS 6 BP 1293 EP 1300 DI 10.1016/j.jamcollsurg.2007.03.024 PG 8 WC Surgery SC Surgery GA 177KT UT WOS:000247152700021 PM 17544087 ER PT J AU Soncini, JA Maserejian, NN Trachtenberg, F Tavares, M Hayes, C AF Soncini, Jennifer Ann Maserejian, Nancy Nairi Trachtenberg, Felicia Tavares, Mary Hayes, Catherine TI The. longevity of amalgam versus compomer/composite restorations in posterior primary and permanent teeth - Findings from the new England children's amalgam trial SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE dental amalgam; resin-based composites; compomers dentition; primary; dentition; permanent; clinical trial ID RANDOMIZED CLINICAL-TRIAL; MODIFIED COMPOSITE RESINS; CLASS-II RESTORATIONS; DENTAL AMALGAM; PRIMARY MOLARS; GLASS-IONOMER; REPLACEMENT; PLACEMENT; COMPOMER; REPAIR AB Background. Limited information is available from randomized clinical trials comparing the longevity of amalgam and resin-based compomer/composite resorations. The authors compared replacement rates of these types of restorations in posterior teeth during the five-year follow-up of the New England Children's Amalgam Trial. Methods. The authors randomized children aged 6 to 10 years who had two or more posterior occlusal carious lesions into groups that received amalgam (n = 267) or composer (primary teeth)/composite (permanent teeth) (n = 267) restorations and followed them up semiannually. They compared the longevity of restorations placed on all posterior surfaces using random effects survival analysis. Results. The average +/- standard deviation follow-up was 2.8 +/- 1.4 years for primary toothe restorations and 3.4 +/- 1.9 years for permanent tooth restorations. In primary teeth, the replacement rate was 5.8 percent of compomers versus 4.0 percent of amalgams (P = .10), with 3.0 percent versus 0.5 percent (P = .002), respectively, due to recurrent caries. In permanent teeth, the replacement rate was 14.9 percent of composites versus 10.8 percent of amalgams (P = .45), and the repair rate was 2.8 percent of composites versus 0.4 percent of amalgams (P = .02). Conclusion. Although the overall difference in longevity was not statistically significant, compomer was replaced significantly mopre frequently owing to recurrent caries, and composite restorations required seven times as many repairs as did amalgam restorations. C1 New England Res Inst, Watertown, MA 02472 USA. Boston Univ, Sch Dent Med, Dept Pediat Dent, Boston, MA 02215 USA. Forsyth Inst, Boston, MA USA. Tufts Univ, Sch Dent Med, Dept Publ Hlth & Community Serv, Medford, MA 02155 USA. RP Maserejian, NN (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM nmaserejian@neriscience.com FU NIDCR NIH HHS [U01 DE11886] NR 45 TC 111 Z9 113 U1 1 U2 22 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUN PY 2007 VL 138 IS 6 BP 763 EP 772 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 178PJ UT WOS:000247232300017 PM 17545265 ER PT J AU Diem, SJ Blackwell, TL Stone, KL Yaffe, K Cauley, JA Whooley, MA Ensrud, KE AF Diem, Susan J. Blackwell, Terri L. Stone, Katie L. Yaffe, Kristine Cauley, Jane A. Whooley, Mary A. Ensrud, Kristine E. CA Study Osteoporotic Fractures TI Depressive symptoms and rates of bone loss at the hip in older women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res DE depression; bone mineral density; osteoporosis ID MINERAL DENSITY; MAJOR DEPRESSION; LOSS INCREASE; RISK-FACTORS; AGE; OSTEOPOROSIS; SEROTONIN; COMMUNITY; FRACTURE; MEN AB Objectives: To ascertain whether depressive symptoms are associated with increased rates of bone loss at the hip. Design: Population-based prospective cohort study. Setting: Four clinical centers in the United States. Participants: Four thousand one hundred seventy-seven community-dwelling women, aged 69 and older, enrolled in the Study of Osteoporotic Fractures. Measurements: Depressive symptoms were assessed using the Geriatric Depression Scale (GDS). Subjects were categorized as depressed if their GDS score was 6 or greater at the fourth examination. Bone mineral density (BMD) at the hip was measured using dual-energy x-ray absorptiometry at the fourth and sixth examinations (average 4.4 years between examinations). Use of antidepressant medications was assessed by interview and verified from medication containers at the fourth and sixth examinations of the Study of Osteoporotic Fractures. A computerized dictionary was used to categorize type of medication. Results: In age-adjusted models, mean total hip BMD decreased 0.69%/year in 3,977 women with a GDS score of less than 6, compared with 0.96%/year in 200 women with a GDS score of 6 or greater (P <.01). Results were not substantially altered when adjusted for potential confounders and when users of antidepressants were excluded from the analysis. Conclusion: Depression, as defined by a GDS score of 6 or greater, was associated with an increased rate of bone loss at the hip in this cohort of older women. Clinicians should be aware of a possible increased rate of bone loss in older, depressed women. C1 Univ Minnesota, Epidemiol Clin Res Ctr, Dept Med, Div Epidemiol & Community Hlth, Minneapolis, MN 55415 USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA. RP Diem, SJ (reprint author), Univ Minnesota, Epidemiol Clin Res Ctr, Dept Med, Div Epidemiol & Community Hlth, 1100 Washington Ave S,Suite 201, Minneapolis, MN 55415 USA. EM sdiem@umn.edu RI Diem, Susan/B-6479-2013; Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [AG05407, AG08415, AG05394]; NIAMS NIH HHS [AR35582, AR35583, AR35584] NR 44 TC 42 Z9 43 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2007 VL 55 IS 6 BP 824 EP 831 DI 10.1111/j.1532-5415.2007.01194.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 172HI UT WOS:000246794400003 PM 17537081 ER PT J AU Sun, BC Hoffman, JR Mangione, CM Mower, WR AF Sun, Benjamin C. Hoffman, Jerome R. Mangione, Carol M. Mower, William R. TI Older age predicts short-term, serious events after syncope SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE syncope; prognosis; risk predictors ID RISK STRATIFICATION; UNEXPLAINED SYNCOPE; EMERGENCY; SCORE AB Objectives: To assess the relationship between age and 14-day serious events after an emergency department (ED) visit for syncope. Design: One-year prospective cohort study. Setting: Single academic ED. Participants: Adult patients with an ED complaint of syncope or near-syncope. Measurements: Treating physicians prospectively recorded the presence or absence of potential risk factors for serious clinical events. Patients were contacted by telephone at 14 days for a structured interview. A three-physician panel reviewed ED charts, hospital records, and telephone interview forms to identify predefined events. The primary outcome included any 14-day predefined event. A secondary outcome included any 14-day predefined event that was first diagnosed after the initial ED visit. Age was analyzed in 20-year intervals. Multivariate logistic regression controlled for baseline demographic, comorbidity, and electrocardiogram data. Results: Of 592 eligible patients, 477 (81%) provided informed consent. Follow-up was successfully obtained for 463 (97%) patients. The age range was 18 to 96, and 47% of patients were aged 60 and older. There were 80 (17%) patients who had a 14-day event, including 18 (4%) with a delayed diagnosis. Compared with patients aged 18 to 39, the adjusted odds ratio (OR) of a serious outcome was 2.7 (95% confidence interval (CI)=0.9-8.4) for patient aged 40 to 59, 3.8 (95% CI=1.3-12) for patients aged 60 to 79, and 3.8 (95% CI=1.2-12) for patients aged 80 and older. Conclusion: Age of 60 and older is strongly associated with short-term serious events after an ED visit for syncope. C1 W Los Angeles Vet Affairs Med Ctr, Off 3214A, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Emergency Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Sun, BC (reprint author), W Los Angeles Vet Affairs Med Ctr, Off 3214A, Dept Med, Mail Stop 111,Bldg 500,Wing 3E,11301 Wilshire Blv, Los Angeles, CA 90073 USA. EM bsun@post.harvard.edu FU NIA NIH HHS [K12 AG001004, AG02004] NR 15 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 2007 VL 55 IS 6 BP 907 EP 912 DI 10.1111/j.1532-5415.2007.01188.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 172HI UT WOS:000246794400014 PM 17537092 ER PT J AU Flaherty, JH Rudolph, J Shay, K Kamholz, B Boockvar, KS Shaughnessy, M Shapiro, R Stein, J Weir, C Edes, T AF Flaherty, Joseph H. Rudolph, James Shay, Ken Kamholz, Barbara Boockvar, Kenneth S. Shaughnessy, Marianne Shapiro, Rita Stein, Joan Weir, Charlene Edes, Thomas TI Delirium is a serious and under recognized problem: Why assessment of mental status should be the sixth vital sign SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Editorial Material ID POOR FUNCTIONAL RECOVERY; RISK-FACTORS; PROGNOSTIC-SIGNIFICANCE; MEDICAL INPATIENTS; OLDER PERSONS; HIP FRACTURE; CARE; SEVERITY; SYMPTOMS; OUTCOMES C1 St Louis Univ, Sch Med, Div Geriatr, St Louis, MO 63104 USA. St Louis VA Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO USA. Harvard Univ, Ctr Geriatr Res Educ & Clin, VA Boston Hlth Care Syst, Div Aging,Brigham & Womens Hosp,Dept Med, Boston, MA USA. VA Med Ctr, Off Geriatr & Extended Care, Ann Arbor, MI USA. Univ Michigan, VA Ann Arbor Hlth Syst, Ann Arbor, MI 48109 USA. James J Peter VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. Baltimore VA Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. VA Chicago Hlth Care Syst, Chicago, IL USA. VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. Salt Lake City VA Med Ctr, Ctr Geriatr Res Educ & Clin, Salt Lake City, UT USA. US Dept Vet Affairs, Off Geriatr & Extended Care, Washington, DC USA. RP Flaherty, JH (reprint author), St Louis Univ, Sch Med, Div Geriatr, 1402 S Grand Blvd,Room M238, St Louis, MO 63104 USA. EM Flaherty@slu.edu OI Boockvar, Kenneth/0000-0003-1165-5558 NR 39 TC 76 Z9 77 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JUN PY 2007 VL 8 IS 5 BP 273 EP 275 DI 10.1016/j.jamda.2007.03.006 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 186UO UT WOS:000247804000001 PM 17570303 ER PT J AU Beeri, R Streckenbach, SC Isselbacher, EM Akins, CW Vlahakes, GJ Adams, MS Levine, RA AF Beeri, Ronen Streckenbach, Scott C. Isselbacher, Eric M. Akins, Cary W. Vlahakes, Gus J. Adams, Mark S. Levine, Robert A. TI The crossed swords sign: Insights into the dilemma of repair in bileaflet mitral valve prolapse SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID MULTIPLANE TRANSESOPHAGEAL ECHOCARDIOGRAPHY; DEGENERATIVE DISEASE; POSTERIOR LEAFLET; JET DIRECTION; REGURGITATION; DOPPLER; REPLACEMENT; GUIDELINES; SURGERY; CHORDAE AB Background: The need for bileaflet repair in bileaflet mitral. valve prolapse (MVP) remains controversial. Will anterior leaflet prolapse resolve with posterior leaflet repair or should both leaflets be addressed? Single-leaflet MVP produces oppositely directed mitral regurgitant jets. Some patients show two crossed jets oppositely directed from the coaptation zone. We hypothesized that these indicate bileaflet lesions requiring complex repair. Methods: Echocardiograms and surgical reports of 52 consecutive patients with MVP undergoing surgery were reviewed. Results: First, all 14 patients with two oppositely directed jets had prolapse of more than one leaflet. Each jet was related to discrete leaflet distortions causing malcoaptation. Six underwent valve replacement. Seven had both leaflets repaired. One had posterior leaflet repair and annuloplasty, with persistent mitral regurgitation requiring valve replacement. Second, 36 of 38 patients with single jets had single-leaflet MVP. One underwent replacement; all others did well with single-leaflet repair. Two patients with bileaflet MVP but only one jet did well with single-leaflet repair or annuloplasty. Conclusion: This crossed swords sign is an important clue to bileaflet mechanism of mitral regurgitation in MVP, associated with complex repair procedures. Thus, it provides a clue in the dilemma of bileaflet versus single-leaflet repair. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Anesthesia, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Surg Unit, Boston, MA 02114 USA. RP Levine, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Anesthesia, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM rlevine@partners.org RI Beeri, Ronen/A-4035-2009 OI Beeri, Ronen/0000-0002-8014-0702 NR 32 TC 1 Z9 1 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD JUN PY 2007 VL 20 IS 6 BP 698 EP 702 DI 10.1016/j.echo.2006.11.030 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176NB UT WOS:000247090900003 PM 17543739 ER PT J AU Balkovetz, DF AF Balkovetz, Daniel F. TI Opening pandora's box in the tight junction SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID MEMBRANE-PROTEINS; EXPRESSION; CYCLOSPORINE; CELLS; CLAUDIN-2 C1 Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. Univ Alabama, Dept Med, Birmingham, AL 35233 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35233 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35233 USA. RP Balkovetz, DF (reprint author), 668 LHRB,1530 3rd Ave S, Birmingham, AL 35294 USA. NR 13 TC 3 Z9 4 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2007 VL 18 IS 6 BP 1624 EP 1625 DI 10.1681/ASN.2007040403 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 174OV UT WOS:000246952700002 PM 17513323 ER PT J AU Johansen, KL AF Johansen, Kirsten L. TI Exercise in the end-stage renal disease population SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID QUALITY-OF-LIFE; MAINTENANCE HEMODIALYSIS-PATIENTS; RANDOMIZED CONTROLLED-TRIAL; DIALYSIS PATIENTS; REVERSE EPIDEMIOLOGY; PHYSICAL PERFORMANCE; PERITONEAL-DIALYSIS; SKELETAL-MUSCLE; CARDIOVASCULAR COMPLICATIONS; REHABILITATION PROGRAMS AB Many of the known benefits of exercise in the general population are of particular relevance to the ESRD population. In addition, the poor physical functioning that is experienced by patients who are on dialysis is potentially addressable through exercise interventions. The study of exercise in the ESRD population dates back almost 30 yr, and numerous interventions, including aerobic training, resistance exercise training, and combined training programs, have reported beneficial effects. Recently, interventions during hemodialysis sessions have become more popular and have been shown to be safe. The risks of exercise in this population have not been rigorously studied, but there have been no reports of serious injury as a result of participation in an exercise training program. It is time that we incorporate exercise into the routine care of patients who are on dialysis, but identification of an optimal training regimen or regimens, according to patient characteristics or needs, is still needed to facilitate implementation of exercise programs. C1 San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu NR 90 TC 109 Z9 116 U1 3 U2 9 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2007 VL 18 IS 6 BP 1845 EP 1854 DI 10.1681/ASN.2007010009 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 174OV UT WOS:000246952700028 PM 17442789 ER PT J AU Kumbhani, DJ Healey, NA Thatte, HS Nawas, S Crittenden, MD Birjiniuk, V Treanor, PR Khuri, SF AF Kumbhani, Dharam J. Healey, Nancy A. Thatte, Hemant S. Nawas, Sammy Crittenden, Michael D. Birjiniuk, Vladimir Treanor, Patrick R. Khuri, Shukri F. TI Patients with diabetes mellitus undergoing cardiac surgery are at greater risk for developing intraoperative myocardial acidosis SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc ID LONG-TERM SURVIVAL; BYPASS; PH; ISCHEMIA; PCO2; DOG AB Objective: In patients undergoing cardiac surgery, intraoperative myocardial acidosis, which quantifies regional myocardial ischemia, has been shown to increase the risk of adverse postoperative outcomes. In this study, we sought to determine the course of intraoperative myocardial acidosis and its impact on postoperative survival in patients with diabetes mellitus undergoing cardiac surgery. Methods: Intraoperative myocardial tissue pH(37C) was continuously measured in the anterior and posterior left ventricular walls in 264 patients undergoing cardiac surgery; 74 (28.0%) of the patients had diabetes (insulin-dependent diabetes: 54%; non-insulin dependent diabetes: 46%). The shortest time required to reach intraoperative myocardial tissue pH < 6.34 during aortic occlusion and > 6.73 during reperfusion were compared in 3 patient groups: insulin-dependent, non-insulin dependent, and nondiabetic. These pH thresholds have been demonstrated to be associated with adverse postoperative long-term survival. Results: The median times to reach intraoperative myocardial tissue pH(37C) < 6.34 during aortic occlusion were 14, 23, and 36 minutes in the insulin-dependent, non-insulin dependent, and non-diabetic groups, respectively (P =.003). The time taken to reach intraoperative myocardial tissue pH(37C) > 6.73 during reperfusion was similar between the 3 groups. After adjusting for relevant pre- and intraoperative parameters, the risk of developing intraoperative myocardial tissue pH < 6.34 during aortic occlusion was 73% higher in patients with insulin-dependent diabetes mellitus (P = .022) but the same in with patients with non-insulin dependent diabetes mellitus (P = .98) when compared with patients without diabetes. Patients with insulin-dependent diabetes mellitus also had nearly threefold decrease in long-term survival compared with that of patients without diabetes (P = .0007). Conclusions: Patients with insulin-dependent diabetes mellitus undergoing cardiac surgery are at a greater risk of developing intraoperative myocardial acidosis/ischemia and of decreased survival postoperatively compared with patients without diabetes. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Surg Serv, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM shukri.khuri@med.va.gov NR 29 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 2007 VL 133 IS 6 BP 1566 EP 1572 DI 10.1016/j.jtcvs.2006.11.047 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 175HS UT WOS:000247005300033 PM 17532958 ER PT J AU Verheugt, FWA Montalescot, G Sabatine, MS Soulat, L Lambert, Y Lapostolle, F Adgey, J Cannon, CP AF Verheugt, Freek W. A. Montalescot, Gilles Sabatine, Marc S. Soulat, Louis Lambert, Yves Lapostolle, Frederic Adgey, Jennifer Cannon, Christopher P. TI Prehospital fibrinolysis with dual antiplatelet therapy in ST-elevation acute myocardial infarction: a substudy of the randomized double blind CLARITY-TIMI 28 trial SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; MOLECULAR-WEIGHT HEPARIN; UNFRACTIONATED HEPARIN; PRIMARY ANGIOPLASTY; CORONARY THROMBOLYSIS; IIB/IIIA INHIBITION; SEGMENT ELEVATION; ASPIRIN; ENOXAPARIN; REOCCLUSION AB Background Fibrinolytic therapy for acute ST-elevation myocardial infarction (STEMI) is frequently limited by delays in administration and by incomplete reperfusion or reocclusion of the infarct-related artery. Intensified prehospital management of STEMI may shorten time to treatment and improve outcomes. Methods We carried out a prospective substudy in 11 ambulance systems in 216 of the 3,491 patients with STEMI who were enrolled in the CLARITY-TIMI 28 trial. They were randomized in the ambulance to clopidogrel (n = 109) or placebo (n = 107) along with fibrinolysis, aspirin, and heparin. The primary endpoint was the composite of an occluded infarct-related artery (TIMI flow grade 0 or 1), or death or recurrent myocardial infarction before angiography. Results All patients received a fibrin-specific lytic and the baseline characteristics in both groups were comparable. The incidence of the primary endpoint was 16.5% in the clopidogrel-treated and 27.1% in the placebo patients (adj OR 0.62, 95% CI 0.31-1.21, p = 0.16), an effect that was consistent with the effects seen in the in-hospital patients in the main CLARITY-TIMI 28 trial. Prehospital clopidogrel therapy reduced the incidence of an occluded infarct-related artery on the predischarge angiogram (11.8% vs. 22.3%, adj OR 0.52, 95% CI 0.24-1.13, p = 0.10). The 30-day incidence of cardiovascular death, recurrent MI or recurrent myocardial ischemia requiring urgent revascularization was 12.8% vs. 14.0% (adj OR 1.07, 95% CI 0.48-2.39, p = 0.87). Early TIMI major bleeding occurred in no clopidogrel patients compared with two placebo patients (1.9%). Conclusions Addition of clopidogrel to medical reperfusion of STEMI with fibrinolysis, heparin, and aspirin before reaching the hospital is feasible in medically equipped ambulances without an apparent increase in bleeding. Furthermore, prehospital clopidogrel tended to show better early coronary patency compared to placebo, a result consistent with that observed in patients randomized in-hospital in the CLARITY-TIMI 28 trial. C1 Univ Med Ctr St Radoud, Heartctr, Dept Cardiol, NL-6525 Nijmegen, Netherlands. Hop La Pitie Salpetriere, Inst Cardiol, Paris, France. Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. SAMU 36, Chateauroux, France. SAMU 78, Versailles, France. SAMU 93, Bobigny, France. Royal Victoria Hosp, Belfast BT12 6BA, Antrim, North Ireland. RP Verheugt, FWA (reprint author), Univ Med Ctr St Radoud, Heartctr, Dept Cardiol, 670 Cardiol,10 Geert Grootepl Zuid, NL-6525 Nijmegen, Netherlands. EM f.verheugt@cardio.umcn.nl RI Verheugt, F.W.A./H-8105-2014 NR 23 TC 20 Z9 23 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JUN PY 2007 VL 23 IS 3 BP 173 EP 179 DI 10.1007/s11239-006-9047-y PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 154HH UT WOS:000245497000002 PM 17160548 ER PT J AU Dunn, NJ Rehm, LP Schillaci, J Souchek, J Mehta, P Ashton, CM Yanasak, E Hamilton, JD AF Dunn, Nancy Jo Rehm, Lynn P. Schillaci, Jeanne Souchek, Julianne Mehta, Paras Ashton, Carol M. Yanasak, Elisia Hamilton, Joseph D. TI A randomized trial of self-management and psychoeducational group therapies for comorbid chronic posttraumatic stress disorder and depressive disorder SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-for-Psychotherapy-Research CY JUN 25, 2002 CL Santa Barbara, CA SP Soc Psychotherapy Res ID COLLABORATIVE RESEARCH-PROGRAM; COGNITIVE THERAPY; RATING SCALE; CLINICIAN; VETERANS AB The authors randomized 101 male veterans with chronic combat-related posttraumatic stress disorder (PTSD) and depressive disorder to an evidence-based depression treatment (self-management therapy; n = 51) or active-control therapy (n = 50). Main outcome measures for efficacy, using intention-to-treat analyses, were subjective and objective PTSD and depression scales at pretest, posttest, and 3-, 6-, and 12-month follow-up. Other measures included treatment compliance, satisfaction, treatment-targeted constructs, functioning, service utilization, and costs. Self-management therapy modestly greater improvement on depression symptoms at treatment completion disappeared on follow-up. No other differences on symptoms or functioning appeared, although psychiatric outpatient utilization and overall outpatient costs were lower with self-management therapy. Despite success in other depressed populations, self-management therapy produced no clinically significant effect in depression with chronic PTSD. C1 Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. Ctr Qual Care & Utilizat Studies, Houston, TX USA. Vet Affairs S Cent Mental Illness Res Educ & Clin, MIRECC, Houston, TX USA. Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Univ Houston, Dept Psychol, Houston, TX USA. VeriCare, San Diego, CA USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Vet Affairs Puget Sound Hlth Care Syst, Tacoma, WA USA. RP Dunn, NJ (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,Mental Hlth Care Line 116MHCL-, Houston, TX 77030 USA. EM ndunn@bcm.tmc.edu RI Mehta, Paras/G-3180-2010 OI Mehta, Paras/0000-0002-7378-3179 NR 36 TC 29 Z9 30 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2007 VL 20 IS 3 BP 221 EP 237 DI 10.1002/jts.20214 PG 17 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 186RF UT WOS:000247795100001 PM 17598141 ER PT J AU Simpson, TL Kaysen, D Bowen, S MacPherson, LM Chawla, N Blume, A Marlatt, GA Larimer, M AF Simpson, T. L. Kaysen, D. Bowen, S. MacPherson, L. M. Chawla, N. Blume, A. Marlatt, G. A. Larimer, M. TI PTSD symptoms, substance use, and Vipassana meditation among incarcerated individuals SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; EXPERIENTIAL AVOIDANCE; ALCOHOL DEPENDENCE; ABUSE; WOMEN; THERAPY; COMORBIDITY; RECIDIVISM; PREVALENCE; REDUCTION AB The present study evaluated whether Posttraumatic Stress Disorder (PTSD) symptom severity was associated with participation and treatment outcomes comparing a Vipassana meditation course to treatment a; usual in an incarcerated sample. This study utilizes secondary data. The original study demonstrated that Vipassana meditation is associated with reductions in substance use. The present study found that PTSD symptom severity did not differ significantly between those who did and did not volunteer to take the course. Participation in the Vipassana course was associated with significantly greater reductions in substance use than treatment as usual, regardless of PTSD symptom severity levels. These results suggest that Vipassana meditation is worthy of further study for those with comorbid P TSD and substance use problems. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ N Carolina, Dept Psychol, Charlotte, NC 28223 USA. RP Simpson, TL (reprint author), 1660 S Columbian Way ATC-116-S, Seattle, WA 98108 USA. EM tracey.simpson@va.gov FU NIAAA NIH HHS [1 R21 AA13054-01] NR 51 TC 38 Z9 41 U1 2 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2007 VL 20 IS 3 BP 239 EP 249 DI 10.1002/jts.20209 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 186RF UT WOS:000247795100002 PM 17597132 ER PT J AU Neria, Y Gross, R Litz, B Maguen, S Insel, B Seirmarco, G Rosenfeld, H Suh, EJ Kishon, R Cook, J Marshall, RD AF Neria, Yuval Gross, Raz Litz, Brett Maguen, Shira Insel, Beverly Seirmarco, Gretchen Rosenfeld, Helena Suh, Eun Jung Kishon, Ronit Cook, Joan Marshall, Randall D. TI Prevalence and psychological correlates of complicated grief among bereaved adults 2.5-3.5 years after September 11th attacks SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; NEW-YORK-CITY; TRAUMATIC GRIEF; TERRORIST ATTACKS; PTSD CHECKLIST; TELEVISION IMAGES; CIVILIAN VERSION; PRIMARY-CARE; VALIDATION; DEPRESSION AB A Web-based survey of adults who experienced loss during the September 11, 2001, terrorist attacks was conducted to examine the prevalence and correlates of complicated grief (CG) 2.5-3.5 years after the attacks. Forty-three percent of a study group of 704 bereaved adults across the United States screened positive for CG. In multivariate analyses, CG was associated with female gender, loss of a child death of deceased at the World Trade Center, and live exposure to coverage of the attacks on television. Posttraumatic stress disorder, major depression, anxiety, suicidal ideation, and increase in post-9/11 smoking were common among participants with CG. A majority of the participants with CG reported receiving grief counseling and psychiatric medication after 9/11. Clinical and policy implications are discussed. C1 New York State Psychiat Inst & Hosp, Unit 69, New York, NY 10032 USA. Columbia Univ, Med Ctr, Dept Psychiat, New York, NY USA. Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY USA. VA BHS, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Neria, Y (reprint author), New York State Psychiat Inst & Hosp, Unit 69, 1051 Riverside Dr, New York, NY 10032 USA. EM ny126@columbia.edu NR 72 TC 81 Z9 83 U1 8 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JUN PY 2007 VL 20 IS 3 BP 251 EP 262 DI 10.1002/jts.20223 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 186RF UT WOS:000247795100003 PM 17597124 ER PT J AU Pontari, MA Joyce, GF Wise, M McNaughton-Collins, M AF Pontari, Michel A. Joyce, Geoffrey F. Wise, Matthew McNaughton-Collins, Mary CA Urologic Dis Amer Project TI Prostatitis SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatitis; health care costs; prevalence; cost and cost analysis ID MEN; PREVALENCE; SYMPTOMS; CLASSIFICATION; DEFINITION; COMMUNITY; DISEASES; PAIN AB Purpose: We quantified the burden of prostatitis in the United States by identifying trends in the use of health care resources and estimating the economic impact of the disease. Materials and Methods: The analytical methods used to generate these results were described previously. Results: The rate of national inpatient hospitalizations for a diagnosis of prostatitis decreased by 21% between 1994 and 2000. Hospitalization rates were 2 to 2.5 times higher for Medicare beneficiaries with a 42% decrease between 1992 and 2001. Combined physician outpatient and hospital outpatient visits revealed an age adjusted, annualized visit rate for prostatitis of 1,798/100,000 population. More than 6% of visits with a primary diagnosis of prostatitis had a concomitant diagnosis of benign prostatic hyperplasia. The most common medications associated with any visits for prostatitis were quinolones (annualized rate 319/100,000 population) and the rate remained about the same even after visits for infectious prostatitis were removed from the data. The cost of prostatitis was about $84 million annually, exclusive of pharmaceutical spending. Of 897 privately insured men with a medical claim for prostatitis in 2002, 14% missed some work because of the condition. Conclusions: Overall spending in the United States for the diagnosis and management of prostatitis, exclusive of pharmaceutical spending, totaled $84 million in 2000 and it appears to be increasing with time. Given the extensive gaps in our understanding of the diagnosis of and treatment for prostatitis, many of these expenditures may represent a waste of resources. C1 Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RAND Hlth, Santa Monica, CA USA. Temple Univ, Sch Med, Dept Urol, Philadelphia, PA 19122 USA. RP McNaughton-Collins, M (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM mmenaughtoncollins@partners.org FU NIDDK NIH HHS [N01 DK 12460] NR 17 TC 20 Z9 21 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2007 VL 177 IS 6 BP 2050 EP 2057 DI 10.1016/j.juro.2007.01.128 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 170BJ UT WOS:000246635800012 PM 17509285 ER PT J AU Garzotto, M AF Garzotto, Mark TI Determining D sing intervals for luteinizing hormone releasing hormone agonists based on serum testosterone levels: A prospective study - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Urol, Portland, OR 97201 USA. RP Garzotto, M (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Urol, Portland, OR 97201 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2007 VL 177 IS 6 BP 2135 EP 2135 DI 10.1016/j.juro.2007.01.261 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 170BJ UT WOS:000246635800026 ER PT J AU Oh, WK AF Oh, William K. TI A prospective, open label, randomized phase II trial of weekly docetaxel versus weekly vinorelbine as first line chemotherapy in patients with androgen independent prostate cancer - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Oh, WK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2007 VL 177 IS 6 BP 2145 EP 2145 DI 10.1016/j.juro.2007.01.265 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 170BJ UT WOS:000246635800030 ER PT J AU Pomerantz, M Manola, J Taplin, ME Bubley, G Inman, M Lowell, J Beard, C Kantoff, PW Oh, WK AF Pomerantz, Mark Manola, Judith Taplin, Mary-Ellen Bubley, Glenn Inman, Margaret Lowell, Jennifer Beard, Clair Kantoff, Philip W. Oh, William K. TI Phase II study of low dose and high dose conjugated estrogen for androgen independent prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; estrogens; estrogens; conjugated (USP) ID DIETHYLSTILBESTROL DIPHOSPHATE; TRIAL; CASTRATION AB Purpose: Although estrogens have known antitumor activity in androgen independent prostate cancer, the best studied agent, diethylstilbestrol, is no longer commercially available in the United States. We tested 2 doses of the conjugated estrogen Premarin (R) in patients with androgen independent prostate cancer to determine the efficacy and safety of this widely available medication. Materials and Methods: A total of 45 patients with progressive androgen independent prostate cancer were randomly assigned to receive Premarin 1.25 mg once (17) or 3 times (28) daily. Warfarin 1 mg daily was administered to all patients to minimize risk of thromboembolism. Low dose prophylactic breast irradiation was administered to most patients. Results: Of the patients receiving high dose Premarin 25% achieved a 50% or greater reduction in prostate specific antigen. No patients treated with low dose Premarin reached a 50% reduction in prostate specific antigen. After 3 months of treatment, 11 patients (39.3%) on the high dose arm and 6 patients (35.3%) on the low dose arm showed no signs of progression. Three patients (6.7%) had a thromboembolic event. No significant gynecomastia was noted. A significant difference in dehydroepiandrosterone sulfate levels was detected between those who did and did not respond to Premarin (p = 0.03). Conclusions: High dose Premarin resulted in prostate specific antigen decreases of 50% or greater in 25% of patients with androgen independent prostate cancer. More than a third of patients receiving high or low dose Premarin maintained stable disease for at least 3 months. With concurrent warfarin 1 mg treatment, 6.7% experienced thromboembolic complications. Premarin 1.25 mg 3 times daily is a reasonable therapeutic option for patients with androgen independent disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Oh, WK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St,Dana Bldg 1230, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 16 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2007 VL 177 IS 6 BP 2146 EP 2150 DI 10.1016/j.juro.2007.01.119 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 170BJ UT WOS:000246635800031 PM 17509304 ER PT J AU Powell, RJ Sidawy, AN Watkins, MT AF Powell, Richard J. Sidawy, Anton N. Watkins, Michael T. TI Current topics in clinical and basic vascular research - Preface SO JOURNAL OF VASCULAR SURGERY LA English DT Editorial Material C1 Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Lebanon, NH 03756 USA. Vet Adm Med Ctr, Washington, DC 20422 USA. Harvard Univ, Massachusetts Gen Hosp, Div Vasc Surg, Cambridge, MA 02138 USA. RP Powell, RJ (reprint author), Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Richard.J.Powell@Hitchcock.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2007 VL 45 SU A BP 1A EP 1A DI 10.1016/j.jvs.2007.02.059 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 175IR UT WOS:000247007800001 ER PT J AU Atkins, MD Kwolek, CJ LaMuraglia, GM Brewster, DC Chung, TK Cambria, RP AF Atkins, Marvin D. Kwolek, Christopher J. LaMuraglia, Glenn M. Brewster, David C. Chung, Thomas K. Cambria, Richard P. TI Surgical revascularization versus endovascular therapy for chronic mesenteric ischemia: A comparative experience SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 01-04, 2006 CL Philadelphia, PA SP Soc Vasc Surg ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; INTESTINAL ISCHEMIA; LATE OUTCOMES; FOLLOW-UP; ARTERY; DISEASE; MANAGEMENT; STENOSES; BYPASS; RISK AB Introduction: Endovascular therapy (percutaneous transluminal angioplasty [PTA] with stenting) has been increasingly applied in patients with chronic mesenteric ischemia (CMI) to avoid morbidities associated with open repair (OR). The purpose of this study was to compare outcomes of PTA/Stent vs OR in patients with symptomatic CMI. Methods: During the interval of January 1991 to December 2005, 80 consecutive patients presenting with symptomatic CMI underwent elective revascularization. Patients with acute mesenteric ischemia or those with mesenteric revascularization performed as part of complex aneurysm repair were excluded. PTA/Stent (with stenting in 87%) was the initial procedure in 31 patients (42 vessels). OR was performed in 49 patients (88 vessels) and consisted of bypass grafting in 31 (63%), transaortic endarterectomy in 7 (14%), patch angioplasty in 4 (8%), or combined in 7 (15%). Mean follow-up was 15 months in the PTA/Stent group and 42 months in the OR cohort. Study end points included perioperative morbidity, mortality, late survival (Kaplan-Meier), and symptomatic and radiographic recurrence. Results: Baseline comorbidities, with the exception of heart disease (P = .025) and serum albumin < 3.5 g/dL (P = .025), were similar between PTA/Stent and OR patients. The PTA/Stent group had fewer vessels revascularized. (1.5 vs 1.8 vessels, P = .001). Hospital length of stay was less for the PTA/Stent group (5.6 vs 16.7 days, P = .001). No difference was noted in in-hospital major morbidity (4/31 vs 2/49, P = .23) or mortality (1/31 vs 1/49, P = .74). Actuarial survival at 2 years was similar between the groups (88% PTA/Stent vs 74% OF, P = .28). There was no difference in the incidence of symptomatic (7/31 [23%] vs 11/49 [22%], P = .98) or radiographic recurrence (10/31 [32%] vs 18/49 [37%], P =.40) between the two groups. Radiographic primary patency (58% vs 90%, P = .001) and primary assisted patency (65% vs 96%, P < .001) at 1 year were lower in the PTA/Stent group compared with OR. Five (16%) of 31 PTA/Stent patients compared with 11 (22%) of 49 OR patients required a second intervention on at least one index vessel at any time (P = .49). Conclusions: Symptomatic recurrence requiring reintervention is common (overall 16/80 [20%]) after open and endovascular treatment for CMI. PTA/Stent was associated with decreased primary patency, primary assisted patency, and the need for earlier reintervention. In-hospital mortality or major morbidity were similar in patients undergoing PTA/Stent and OR. These findings suggest that OR and PTA/Stent should be applied selectively in CMI patients in accordance with individual patient anatomic and comorbidity considerations. C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg Gen Surg Sci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Cambria, RP (reprint author), WACC 458,15 Parkman St, Boston, MA 02114 USA. EM rcambria@partners.org OI Chung, Thomas/0000-0001-6148-1184 NR 28 TC 88 Z9 96 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2007 VL 45 IS 6 BP 1162 EP 1171 DI 10.1016/j.jvs.2007.01.067 PG 10 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 174GZ UT WOS:000246931500013 PM 17467950 ER PT J AU Dey, B Pancera, M Svehla, K Shu, Y Xiang, SH Vainshtein, J Li, YX Sodroski, J Kwong, PD Mascola, JR Wyatt, R AF Dey, Barna Pancera, Marie Svehla, Krisha Shu, Yuuei Xiang, Shi-Hua Vainshtein, Jeffrey Li, Yuxing Sodroski, Joseph Kwong, Peter D. Mascola, John R. Wyatt, Richard TI Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: Antigenicity, biophysics, and immunogenicity SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; HIV-1 ENVELOPE GLYCOPROTEINS; CD4 BINDING-SITE; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES; PRIMARY ISOLATE; RECEPTOR; EPITOPE; INFECTION; GP41 AB The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations in several gp120 envelope glycoprotein contexts. The gp120 glycoproteins with the T257S-plus-S375W double mutation (T257S+S375W) have a superior antigenic profile compared to the originally identified single S375W replacement in terms of enhanced recognition by the broadly neutralizing CD4 binding-site antibody b12. Isothermal titration calorimetry measuring the entropy of the gp120 interaction with CD4 indicated that the double mutant was also stabilized into the CD4-bound state, with increasing relative fixation between core, full-length monomeric, and full-length trimeric versions of gp120. A significant increase in gp120 affinity for CD4 was also observed for the cavity-filling mutants relative to wild-type gp120. The most conformationally constrained T257S+S375W trimeric gp120 proteins were selected for immunogenicity analysis in rabbits and displayed a trend of improvement relative to their wild-type counterparts in terms of eliciting neutralizing antibodies. Together, the results suggest that conformational stabilization may improve the ability of gp120 to elicit neutralizing antibodies. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wyatt, R (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 4512, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov FU Intramural NIH HHS NR 49 TC 83 Z9 84 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2007 VL 81 IS 11 BP 5579 EP 5593 DI 10.1128/JVI.02500-06 PG 15 WC Virology SC Virology GA 173II UT WOS:000246866300015 PM 17360741 ER PT J AU Velu, V Kannanganat, S Ibegbu, C Chennareddi, L Villinger, F Freeman, GJ Ahmed, R Amara, RR AF Velu, Vijayakumar Kannanganat, Sunil Ibegbu, Chris Chennareddi, Lakshmi Villinger, Francois Freeman, Gordon J. Ahmed, Rafi Amara, Rama Rao TI Elevated expression levels of inhibitory receptor programmed death 1 on simian immunodeficiency virus-specific CD8 T cells during chronic infection but not after vaccination SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS MACAQUES; ANTIRETROVIRAL THERAPY; VIRAL PERSISTENCE; IMMUNE-RESPONSES; 89.6P CHALLENGE; VIREMIA; CD4(+); PD-1; DNA; REPLICATION AB Here, we study the temporal expression of the inhibitory receptor programmed death 1 (PD-1) on simian immunodeficiency virus (SIV) Gag-specific T cells following pathogenic SIV infection or following vaccination with a DNA/modified vaccinia virus Ankara (DNA/MVA) vaccine and simian/human immunodeficiency virus (SHIV challenge in macaques. Following infection, the majority (>95%) of Gag-specific CD8 T cells expressed PD-1, and the level of PD-1 expression per cell increased over time. The level of PD-I expression in lymph nodes and rectal mucosal tissue, the major sites of virus replication, was higher compared to blood. In vitro blockade of PD-1 resulted in enhanced proliferation of SIV-specific CD8 as well as CD4 T cells. In contrast, following vaccination, the majority of peak effector Gag-specific CD8 T cells expressed low levels of PD-1, and these levels decreased further as the cells differentiated into memory cells. In addition, following SHIV challenge of these vaccinated macaques, the level of PD-1 expression on Gag-specific CD8 T cells correlated positively with plasma viremia. These results demonstrate that SIV-specific CD8 T cells express PD-1 after exposure to antigen but downregulate expression under conditions of antigen clearance and enhance expression under conditions of antigen persistence. They also demonstrate that the level of PD-1 expression per cell rather than the presence or absence of expression plays an important role in regulating CD8 T-cell dysfunction in pathogenic SIV infection. In addition, they demonstrate that similar to HIV infection, the PD-1:PD-1 ligand inhibitory pathway is operational in pathogenic SIV infection, and the macaque/SIV model would be ideal to test the safety and therapeutic benefit of blocking this pathway in vivo. C1 Emory Univ, Yerkes Natl Primate Res Ctr, Dept Immunol & Microbiol, Vaccine Res Ctr, Atlanta, GA 30329 USA. Emory Univ, Dept Pathol, Atlanta, GA 30329 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Amara, RR (reprint author), 954 Gatewood Rd NE, Atlanta, GA 30329 USA. EM rama@rmy.emory.edu OI Velu, Vijayakumar/0000-0003-4238-1924 FU NCRR NIH HHS [P51 RR000165, P51 RR00165]; NHLBI NIH HHS [R01 HL075833]; NIAID NIH HHS [AI56299, P01 AI049364, P01 AI056299, P01 AI49364, P30 AI050409, P30 AI50409, R01 AI057029, R01 AI57029] NR 41 TC 97 Z9 98 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2007 VL 81 IS 11 BP 5819 EP 5828 DI 10.1128/JVI.00024-07 PG 10 WC Virology SC Virology GA 173II UT WOS:000246866300036 PM 17376899 ER PT J AU Frater, AJ Brown, H Oxenius, A Guenthard, HF Hirschel, B Robinson, N Leslie, AJ Payne, R Crawford, H Prendergast, A Brander, C Kiepiela, P Walker, BD Goulder, PJR McLean, A Phillips, RE AF Frater, A. J. Brown, H. Oxenius, A. Guenthard, H. F. Hirschel, B. Robinson, N. Leslie, A. J. Payne, R. Crawford, H. Prendergast, A. Brander, C. Kiepiela, P. Walker, B. D. Goulder, P. J. R. McLean, A. Phillips, R. E. CA Swiss HIV Cohort Study TI Effective T-cell responses select human immunodeficiency virus mutants and slow disease progression SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPHOCYTE RESPONSES; VIROLOGICAL FAILURE; ESCAPE MUTATIONS; VIRAL ESCAPE; FITNESS COST; HLA; HIV; TYPE-1; INFECTION; AIDS AB The possession of some HLA class I molecules is associated with delayed progression to AIDS. The mechanism behind this beneficial effect is unclear. We tested the idea that cytotoxic T-cell responses restricted by advantageous HLA class I molecules impose stronger selection pressures than those restricted by other HLA class I alleles. As a measure of the selection pressure imposed by HLA class I alleles, we determined the extent of HLA class I-associated epitope variation in a cohort of European human immunodeficiency virus (HIV)-positive individuals (n = 84). We validated our findings in a second, distinct cohort of African patients (n = 516). We found that key HIV epitopes restricted by advantageous HLA molecules (1327, 1357, and B51 in European patients and B5703, B5801, and B8101 in African patients) were more frequently mutated in individuals bearing the restricting HLA than in those who lacked the restricting HLA class I molecule. HLA alleles associated with clinical benefit restricted certain epitopes for which the consensus peptides were frequently recognized by the immune response despite the circulating virus's being highly polymorphic. We found a significant inverse correlation between the HLA-associated hazard of disease progression and the mean HLA-associated prevalence of mutations within epitopes (P = 0.028; R-2 = 0.34). We conclude that beneficial HLA class I alleles impose strong selection at key epitopes. This is revealed by the frequent association between effective T-cell responses and circulating viral escape mutants and the rarity of these variants in patients who lack these favorable HLA class I molecules, suggesting a significant pressure to revert. C1 John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford, England. Univ Oxford, Oxford OX1 3SY, England. James Martin 21st Century Sch, Inst Emergent Infect Humans, Oxford OX1 3SY, England. Eidgenossische Tech Hochsch, Inst Microbiol, CH-8092 Zurich, Switzerland. Univ Hosp Zurich, Div Infect Dis, CH-8091 Zurich, Switzerland. Univ Hosp Zurich, Hosp Epiemiol, CH-8091 Zurich, Switzerland. Univ Hosp, Div Infect Dis, CH-1211 Geneva, Switzerland. Nuffield Dept Med, Dept Paediat, Oxford OX1 3SY, England. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogeness Programme, Durban, South Africa. Univ Oxford, Zool Dept, James Martin 21st Century Sch, Inst Emnergent Infect Humans, Oxford OX1 3PS, England. RP Phillips, RE (reprint author), Nuffield Dept Med, Peter Medawar Bldg Pathogen Res,South Parks Rd, Oxford OX1 3SY, England. EM Rodney.Phillips@ndm.ox.ac.uk RI gunthard, huldrych/F-1724-2011; SHCS, only/G-4080-2011; Infektiologie, USZ/A-6921-2011; SHCS, all/G-4072-2011; SHCS, ch/G-4077-2011; Oxenius, Annette/G-7794-2015; OI gunthard, huldrych/0000-0002-1142-6723; Frater, John/0000-0001-7163-7277; Brander, Christian/0000-0002-0548-5778 FU Medical Research Council [G0500384, G108/626]; Wellcome Trust NR 34 TC 73 Z9 73 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2007 VL 81 IS 12 BP 6742 EP 6751 DI 10.1128/JVI.00022-07 PG 10 WC Virology SC Virology GA 175BP UT WOS:000246987500056 PM 17409157 ER PT J AU Cheng, X Liu, YS Irimia, D Demirci, U Yang, LJ Zamir, L Rodriguez, WR Toner, M Bashir, R AF Cheng, Xuanhong Liu, Yi-shao Irimia, Daniel Demirci, Utkan Yang, Liju Zamir, Lee Rodriguez, William R. Toner, Mehmet Bashir, Rashid TI Cell detection and counting through cell lysate impedance spectroscopy in microfluidic devices SO LAB ON A CHIP LA English DT Article ID ON-A-CHIP; REGULATORY VOLUME DECREASE; BACTERIAL METABOLISM; COULTER-COUNTER; BLOOD; FLOW; MANIPULATION; MONONUCLEAR; LEUKOCYTES; BEHAVIOR AB Cell-based microfluidic devices have attracted interest for a wide range of applications. While optical cell counting and flow cytometry-type devices have been reported extensively, sensitive and efficient non-optical methods to detect and quantify cells attached over large surface areas within microdevices are generally lacking. We describe an electrical method for counting cells based on the measurement of changes in conductivity of the surrounding medium due to ions released from surface-immobilized cells within a microfluidic channel. Immobilized cells are lysed using a low conductivity, hypotonic media and the resulting change in impedance is measured using surface patterned electrodes to detect and quantify the number of cells. We found that the bulk solution conductance increases linearly with the number of isolated cells contributing to solution ion concentration. The method of cell lysate impedance spectroscopy is sensitive enough to detect 20 cells mu L-1, and offers a simple and efficient method for detecting and enumerating cells within microfluidic devices for many applications including measurement of CD4 cell counts in HIV patients in resource-limited settings. To our knowledge, this is the most sensitive approach using non-optical setups to enumerate immobilized cells. The microfluidic device, capable of isolating specific cell types from a complex bio-fluidic and quantifying cell number, can serve as a single use cartridge for a hand-held instrument to provide simple, fast and affordable cell counting in point-of-care settings. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Div Aids, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Purdue Univ, Weldon Sch Biomed Engn, Sch Elect Engn & Comp Sci, Birck Nanotechnol Ctr, W Lafayette, IN 47907 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Rodriguez, WR (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. EM wrodriguez@partners.org; mtoner@sbi.org; bashir@purdue.edu OI Irimia, Daniel/0000-0001-7347-2082 FU NIBIB NIH HHS [P41 EB002503] NR 45 TC 92 Z9 94 U1 3 U2 51 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PD JUN PY 2007 VL 7 IS 6 BP 746 EP 755 DI 10.1039/b705082h PG 10 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 183IL UT WOS:000247566400023 PM 17538717 ER PT J AU Komers, R Lindsley, JN Oyama, TT Cohen, DM Anderson, S AF Komers, Radko Lindsley, Jessie N. Oyama, Terry T. Cohen, David M. Anderson, Sharon TI Renal p38 MAP kinase activity in experimental diabetes SO LABORATORY INVESTIGATION LA English DT Article DE diabetic nephropathy; hyperglycemia; p38 mitogen-activated protein kinase; proteinuria; signaling ID ACTIVATED PROTEIN-KINASE; ANGIOTENSINOGEN GENE-EXPRESSION; PROXIMAL TUBULAR CELLS; SIGNAL-TRANSDUCTION PATHWAYS; HUMAN MESANGIAL CELLS; SMOOTH-MUSCLE-CELLS; HIGH GLUCOSE; INDEPENDENT ACTIVATION; ACTIN CYTOSKELETON; MESSENGER-RNA AB Renal cell activity of p38 mitogen-activated protein kinase (p38) is increased in the diabetic milieu. p38 mediates signals relevant for the development of diabetic nephropathy (DN). However, renal p38 in Type 1 diabetes in vivo, particularly in conditions reflecting the differences in metabolic control, and its activity in advanced stages of DN, has received less attention. We examined the p38 pathway in renal cortex of rats with streptozotocin diabetes (4 weeks) with poor (DS), moderate (DM), and intensive (DII) metabolic control, achieved by varying doses of insulin therapy. Renal p38 was also studied in 12-month diabetic rats with established nephropathy (DM12) and compared with age-matched controls. p38 activity (in vitro kinase assay and expression of phosphorylated (active) p38 (P-p38)) was increased in DM and DS rats, as compared with non-diabetic controls, and attenuated by intensive insulin treatment. In all groups, P-p38 was predominantly localized in macula densa cells. Diabetic rats also demonstrated P-p38 immunoreactivity in the distal tubule and glomeruli. Enhanced p38 activity in DS and DM rats was not associated with increases in expression of active mitogen-activated protein kinase 3/6, an activator of p38, but paralleled with increased expression of scaffolding protein transforming growth factor-beta-activated protein kinase 1-binding protein 1. Expression of mitogen-activated protein phosphatase-1 (MKP-1), one of the phosphatases involved in inactivation of mitogen-activated protein kinase signaling, was increased in all diabetic groups, irrespective of metabolic control. Renal p38 activation was also detectable in D12 rats with established albuminuria and glomerulosclerosis. In summary, renal cortical p38 activity was increased in diabetic rats at early and advanced stages of nephropathy, as compared with non-diabetic animals, and attenuated by improved metabolic control. p38 activation in diabetes is likely to occur via multiple pathways and cannot be explained by downregulation of MKP-1. C1 Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. Inst Clin & Expt Med, Ctr Diabet, Prague, Czech Republic. Portland VA Med Ctr, Med Serv, Portland, OR USA. RP Komers, R (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM komersr@ohsu.edu FU NIDDK NIH HHS [DK-52494, DK 063231] NR 40 TC 26 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 2007 VL 87 IS 6 BP 548 EP 558 DI 10.1038/labinvest.3700549 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 168ZA UT WOS:000246561300004 PM 17401436 ER PT J AU Scott, AR Gray, ST AF Scott, Andrew R. Gray, Stacey T. TI Oropharyngeal foreign body after attempted nasal intubation: A case of traumatic middle turbinectomy SO LARYNGOSCOPE LA English DT Article DE nasal intubation; turbinate AB A nasopharyngeal airway, or nasal trumpet, is an adjunctive airway device used to bypass upper airway obstruction at the level of the oral cavity or oropharynx. Although nasal trumpet placement on an awake patient may be uncomfortable, there are no reports of significant trauma from insertion. We present an unusual case of middle turbinate avulsion presenting as a foreign body in the oropharynx after several attempts at placement of a nasopharyngeal airway in an unconscious patient. We hope to raise awareness that nasal intubation in patients with altered consciousness can result in significant nasal trauma, especially after multiple attempts have failed. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Scott, AR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM andrew_scott@meei.harvard.edu NR 5 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 2007 VL 117 IS 6 BP 1094 EP 1095 DI 10.1097/MLG.0b013e318050ca2b PG 2 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 174ET UT WOS:000246925000027 PM 17545872 ER PT J AU Breitkreutz, I Lokhorst, HM Raab, MS van der Holt, B Cremer, FW Herrmann, D Glasmacher, A Schmidt-Wolf, IGH Blau, IW Martin, H Salwender, H Haenel, A Sonneveld, P Goldschmidt, H AF Breitkreutz, I. Lokhorst, H. M. Raab, M. S. van der Holt, B. Cremer, F. W. Herrmann, D. Glasmacher, A. Schmidt-Wolf, I. G. H. Blau, I. W. Martin, H. Salwender, H. Haenel, A. Sonneveld, P. Goldschmidt, H. TI Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield SO LEUKEMIA LA English DT Article DE multiple myeloma; thalidomide; initial therapy; peripheral blood stem cell collection; hematopoetic reconstitution; autologous blood stem cell transplantation ID COLONY-STIMULATING FACTOR; PLUS DEXAMETHASONE; COMBINATION THERAPY; SALVAGE THERAPY; AUTOLOGOUS PBSCT; RANDOMIZED-TRIAL; DRUG-RESISTANCE; TRANSPLANTATION; VAD; DOXORUBICIN AB In a phase III randomized, multicenter study, the Germanspeaking Myeloma-Multicenter Group (GMMG) and the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) group investigated the influence of thalidomide (Thal) on the outcome of peripheral blood stem cell (PBSC) collection in multiple myeloma (MM) before peripheral autologous blood stem cell transplantation (ABSCT). We analyzed the data of 398 myeloma patients after induction with Thal, doxorubicin and dexamethasone (TAD) in comparison with vincristine, doxorubicin and dexamethasone (VAD) followed by mobilization with cyclophosphamide, doxorubicin, dexamethasone (CAD) and PBSC collection. Within both the study groups, patients treated with TAD showed to collect significantly fewer CD34(+) cells compared with VAD (GMMG, TAD: median 9.8 x 10(6)/kg; range 2.0-33.6; VAD: median 10.9 x 10(6)/kg range 3.0-36.0; P = 0.02) (HOVON, TAD: median 7.4 x 10(6)/kg; range 2.0-33.0; VAD: median 9.4 x 10(6)/kg; range 0.0-48.7; P = 0.009). However, engraftment after peripheral autologous stem cell transplantation showed no difference between Thal and VAD groups. We conclude that Thal as a part of induction regimen is associated with better response rates (GMMG-HD3: CR/PR 79%, VAD: CR/PR 58%; HOVON-50: TAD: CR/PR 81%, VAD: CR/PR 61%), but significantly affects the yield of PBSC collection. Nevertheless, the number of total CD34(+) cells collected was sufficient for double autologous transplantation in 82% of the Thal patients, with at least 2.5 x 10(6)/kg CD34(+) cells. C1 Univ Heidelberg, Dept Internal Med 5, Heidelberg, Germany. Univ Utrecht, Med Ctr, Dept Hematol, Utrecht, Netherlands. Erasmus MC, Dr Daniel Den Hoed Canc Ctr, Dept Trials & Stat, HOVON Data Ctr, Rotterdam, Netherlands. Cytonet GmbH, Heidelberg, Germany. Univ Bonn, Dept Internal Med 1, D-5300 Bonn, Germany. Univ Berlin, CBF, Dept Internal Med 3, Berlin, Germany. Univ Frankfurt, Dept Internal Med, D-6000 Frankfurt, Germany. AKA, Dept Internal Med, Hamburg, Germany. Chemnitz GmbH, Dept Internal Med 3, Chemnitz, Germany. Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. RP Breitkreutz, I (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome LIpper Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM Iris_Breitkreutz@dfci.harvard.edu NR 34 TC 40 Z9 41 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 2007 VL 21 IS 6 BP 1294 EP 1299 DI 10.1038/sj.leu.2404661 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 172JD UT WOS:000246799300021 PM 17377586 ER PT J AU Mesa, RA Verstovsek, S Cervantes, F Barosi, G Reilly, JT Dupriez, B Levine, R Le Bousse-Kerdiles, MC Wadleigh, M Campbell, PJ Silver, RT Vannucchi, AM Deeg, HJ Gisslinger, H Thomas, D Odenike, O Solberg, LA Gotlib, J Hexner, E Nimer, SD Kantarjian, H Orazi, A Vardiman, JW Thiele, J Tefferi, A AF Mesa, Ruben A. Verstovsek, Srdan Cervantes, Francisco Barosi, Giovanni Reilly, John T. Dupriez, Brigitte Levine, Ross Le Bousse-Kerdiles, Marie-Caroline Wadleigh, Martha Campbell, Peter J. Silver, Richard T. Vannucchi, Alessandro M. Deeg, H. Joachim Gisslinger, Heinz Thomas, Deborah Odenike, Olatoyosi Solberg, Lawrence A. Gotlib, Jason Hexner, Elizabeth Nimer, Stephen D. Kantarjian, Hagop Orazi, Attilio Vardiman, James W. Thiele, Juergen Tefferi, Ayalew TI Primary myelofibrosis (PMF), post polycythernia vera myelotibrosis (post-PV MF), post essential thrombocythemia myelofibrosis (post-ET MF), blast phase PMF (PMF-BP): Consensus on terminology by the international working group for myelofibrosis research and treatment (IWG-MRT) SO LEUKEMIA RESEARCH LA English DT Editorial Material DE primary myelofibrosis; International Working Group for Myelofibrosis Research and Treatment; IWG-MRT; myeloproliferative disorders; myelofibrosis; myelotibrosis with myeloid metaplasia; chronic idiopathic myelofibrosis ID CHRONIC IDIOPATHIC MYELOFIBROSIS; AGNOGENIC MYELOID METAPLASIA; TYROSINE KINASE JAK2; MYELOPROLIFERATIVE DISORDERS; ACTIVATING MUTATION; PATHOGENESIS; SPLEEN; ANEMIA; CELLS; MICE AB The International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) is comprised of hematologists, hematopathologists, and laboratory scientists and its main goal is to provide a forum for scientific exchange and collaboration. During its first general meeting in April 2006, the IWG-MRT established uniform treatment response criteria for chronic idiopathic myelofibrosis (CIMF); also known as agnogenic myeloid metaplasia (AMM), myelofibrosis with myeloid metaplasia (MMM), and many other names in the hematologic literature. This document summarizes the proceedings from the second meeting of the IWG-MRT, in November 2006, where the group discussed and agreed to standardize the nomenclature referring to CIMF: (i) the term primary myelofibrosis (PMF) was chosen over several other designations including CIMF, AMM, and MMM, (ii) myelofibrosis that develops in the setting of either polycythemia vera (PV) or essential thrombocythemia (ET) will be referred to as post-PV MF and post-ET ME, respectively, and (iii) "leukemic" transformation will be recognized as blast phase disease (PMF-BP, post-PV/ET MF in blast phase). (c) 2007 Elsevier Ltd. All rights reserved. C1 Mayo Clin, Rochester, MN 55905 USA. MD Anderson Canc Ctr, Houston, TX USA. Inst Invest Biomed August Pi Sunyer, Barcelona, Spain. Policlin San Matteo, Ist Ric & Cura Carattere Sci, I-27100 Pavia, Italy. Royal Hallamshire Hosp, Sheffield S10 2JF, S Yorkshire, England. Brigham & Womens Hosp, Boston, MA 02115 USA. Hop Paul Brousse, INSERM, U602, Villejuif, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cambridge, Cambridge, England. Cornell Univ, Weill Med Coll, New York, NY USA. Univ Florence, Florence, Italy. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Med Univ Vienna, Vienna, Austria. Univ Chicago, Chicago, IL 60637 USA. Mayo Clin, Jacksonville, FL 32224 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Penn, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. Univ Cologne, Inst Pathol, D-5000 Cologne, Germany. RP Tefferi, A (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu FU Wellcome Trust [088340] NR 32 TC 143 Z9 150 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JUN PY 2007 VL 31 IS 6 BP 737 EP 740 DI 10.1016/j.leukres.2006.12.002 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 186FJ UT WOS:000247764200002 PM 17210175 ER PT J AU Matthews, AG Finkelstein, DM Betensky, RA AF Matthews, Abigail G. Finkelstein, Dianne M. Betensky, Rebecca A. TI Multivariate logistic regression for familial aggregation in age at disease onset SO LIFETIME DATA ANALYSIS LA English DT Article DE familial association; age at onset; Cancer Genetics Network ID BIVARIATE SURVIVAL-DATA; LIKELIHOOD RATIO TESTS; FAILURE TIME DATA; BREAST-CANCER; MAXIMUM-LIKELIHOOD; TRUNCATED DATA; LIFE-TABLES; MODEL; DISTRIBUTIONS; ASSOCIATION AB Familial aggregation studies seek to identify diseases that cluster in families. These studies are often carried out as a first step in the search for hereditary factors affecting the risk of disease. It is necessary to account for age at disease onset to avoid potential misclassification of family members who are disease-free at the time of study participation or who die before developing disease. This is especially true for late-onset diseases, such as prostate cancer or Alzheimer's disease. We propose a discrete time model that accounts for the age at disease onset and allows the familial association to vary with age and to be modified by covariates, such as pedigree relationship. The parameters of the model have interpretations as conditional log-odds and log-odds ratios, which can be viewed as discrete time conditional cross hazard ratios. These interpretations are appealing for cancer risk assessment. Properties of this model are explored in simulation studies, and the method is applied to a large family study of cancer conducted by the National Cancer Institute-sponsored Cancer Genetics Network (CGN). C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Betensky, RA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM betensky@hsphmail.harvard.edu FU NCI NIH HHS [R01 CA075971, R01 CA 74302, R01 CA 75971, U01 CA78284-04] NR 50 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD JUN PY 2007 VL 13 IS 2 BP 191 EP 209 DI 10.1007/s10985-007-9037-1 PG 19 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 159SV UT WOS:000245887700002 PM 17410428 ER PT J AU Freeman, RB Ruthazer, R Schore, A Mithofer, A Ngyuen, K Agarwal, P Harper, A Edwards, EB AF Freeman, Richard B. Ruthazer, Robin Schore, Anthony Mithofer, Abigail Ngyuen, Khanh Agarwal, Prakhar Harper, Ann Edwards, Erick B. TI Pre-operative ablation is beneficial for HCC candidates waiting for liver transplantation. SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT 13th Annual Congress of the International-Liver-Transplantation-Society CY JUN 20-23, 2007 CL Rio de Janeiro, BRAZIL C1 Tufts Univ, New England Med Ctr, Dept Surg, Div Transplantat, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Gastroenterol Hepatol, Boston, MA 02114 USA. United Network Organ Sharing, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUN PY 2007 VL 13 IS 6 SU 1 MA 192 BP S118 EP S118 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 176KU UT WOS:000247084700193 ER PT J AU Guckelberger, O Micheal, MD Biddinger, SB Schoebel, C Reuter, S Neuhaus, P Kahn, CR Robson, SC AF Guckelberger, Olaf Micheal, M. D. Biddinger, S. B. Schoebel, C. Reuter, S. Neuhaus, P. Kahn, C. R. Robson, S. C. TI Insulinopenia and insulin-resistance delay liver regeneration in mice. SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT 13th Annual Congress of the International-Liver-Transplantation-Society CY JUN 20-23, 2007 CL Rio de Janeiro, BRAZIL C1 Campus Virchow Klinikum, Charite, Dept Gen Visceral & Transplantat Surg, Berlin, Germany. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Gastroenterol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUN PY 2007 VL 13 IS 6 SU 1 MA 145 BP S103 EP S104 PG 2 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 176KU UT WOS:000247084700146 ER PT J AU Schumann, R Hudcova, J AF Schumann, Roman Hudcova, Jana TI Isoelectric BIS (TM) responsive to photic stimulation during OLT for fulminant hepatic failure. SO LIVER TRANSPLANTATION LA English DT Meeting Abstract CT 13th Annual Congress of the International-Liver-Transplantation-Society CY JUN 20-23, 2007 CL Rio de Janeiro, BRAZIL ID BISPECTRAL INDEX C1 Campus Virchow Klinikum, Charite, Dept Visceral & Transplantat Surg, Berlin, Germany. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Gastroenterol, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUN PY 2007 VL 13 IS 6 SU 1 MA 144 BP S103 EP S103 PG 1 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 176KU UT WOS:000247084700145 ER PT J AU Singh, M Rihal, CS Lennon, RJ Spertus, J Rumsfeld, JS Holmes, DR AF Singh, Mandeep Rihal, Charanjit S. Lennon, Ryan J. Spertus, John Rumsfeld, John S. Holmes, David R., Jr. TI Bedside estimation of risk from percutaneous coronary intervention: The new Mayo Clinic risk scores. SO MAYO CLINIC PROCEEDINGS LA English DT Article ID IN-HOSPITAL MORTALITY; OPERATOR VOLUME; COMPLICATIONS; MODELS; STRATIFICATION; PREDICTION; VALIDATION; EXPERIENCE AB Objective: To derive risk models for percutaneous coronary intervention (PCI) outcomes from clinical and laboratory variables available before the procedure so they can be used for preprocedure risk stratification. Patients and Methods: Using the Mayo Clinic registry, we analyzed 9035 PCIs on 7640 unique patients from January 1, 2000, through April 30, 2005. We included only the first PCI per patient (n=7457). Logistic regression was used to model the calculated risk score and major procedural complications. Separate risk models were made for mortality and major adverse cardiovascular events (MACE) derived solely from baseline and laboratory characteristics. Final risk scores for procedural death, defined as any death during the index hospitalization, and MACE contained the same 7 variables (age, myocardial infarction :524 hours, preprocedural shock, serum creatinine level, left ventricular ejection fraction, congestive heart failure, and peripheral artery disease). Results: Models had adequate goodness of fit, and areas under the receiver operating characteristic curve were 0.74 and 0.89 for MACE and procedural death, respectively, indicating excellent overall discrimination. The model was robust across many subgroups, including those undergoing elective PCI, those having diabetes mellitus, and elderly patients. Bootstrap analysis Indicated that the model was not overfit to the available data set. Conclusions: Before coronary angiography is performed, a risk-scoring system based on 7 variables can be used conveniently to predict cardiovascular complications after PCI. This model may be useful for providing patients with individualized, evidence-based estimates of procedural risk as part of the informed consent process. C1 Mayo Clin & Mayo Fdn, Coll Med, Div Cardiovasc Dis, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Coll Med, Div Biostat, Rochester, MN 55905 USA. Mid Amer Heart Inst, Kansas City, MO USA. Denver VA Med Ctr, Div Cardiovasc, Denver, CO USA. RP Singh, M (reprint author), Mayo Clin & Mayo Fdn, Coll Med, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA. EM singh.mandeep@mayo.edu NR 18 TC 64 Z9 64 U1 0 U2 7 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUN PY 2007 VL 82 IS 6 BP 701 EP 708 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 174XT UT WOS:000246976900010 PM 17550750 ER PT J AU Min, LC Wenger, NS Fung, C Chang, JT Ganz, DA Higashi, T Kamberg, CJ MacLean, CH Roth, CP Solomon, DH Young, RT Reuben, DB AF Min, Lillian C. Wenger, Neil S. Fung, Constance Chang, John T. Ganz, David A. Higashi, Takahiro Kamberg, Caren J. MacLean, Catherine H. Roth, Carol P. Solomon, David H. Young, Roy T. Reuben, David B. TI Multimorbidity is associated with better quality of care among vulnerable elders SO MEDICAL CARE LA English DT Article DE multimorbidity; comorbidity; vulnerable elders; quality of care; quality indicators ID OLDER PATIENTS; MEDICAL CONDITIONS; FUNCTIONAL STATUS; BLOOD-PRESSURE; WOMENS HEALTH; MORTALITY; COMMUNITY; PEOPLE; COMORBIDITY; POPULATION AB Background: Older patients with multiple chronic conditions may be at higher risk of receiving poorer overall quality of care compared with those with single or no chronic conditions. Possible reasons include competing guidelines for individual conditions, burden of numerous recommendations, and difficulty implementing treatments for multiple conditions. Objectives: We sought to determine whether coexisting combinations of 8 common chronic conditions (hypertension, coronary artery disease, chronic obstructive pulmonary disease, osteoarthritis, diabetes mellitus, depression, osteoporosis, and having atrial fibrillation or congestive heart failure) are associated with overall quality of care among vulnerable older patients. Materials and Methods: Using an observational cohort study, we enrolled 372 community-dwel ling persons 65 years of age or older who were at increased risk for death or functional decline within 2 years. We included (1) a comprehensive measure (% of quality indicators satisfied) of quality of medical and geriatric care that accounted for patient preference and appropriateness in light of limited life expectancy and advanced dementia, and (2) a measure of multimorbidity, either as a simple count of conditions or as a combination of specific conditions. Results: Multimorbidity was associated with greaer overall quality scores: mean proportion of quality indicators satisfied increased from 47% for elders with none of the prespecified conditions to 59% for those with 5 or 6 conditions (P < 0.0001), after controlling for number of office visits. Patients with greater multimorbidity also received care that was better than would be expected based on the specific set of quality indicators they triggered. Conclusions: Among older persons at increased risk of death or functional decline, multimorbidity results in better, rather than worse, quality of care. C1 Univ Calif Los Angeles, Dept Geriatr Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. RAND Hlth, Santa Monica, CA USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, STAR Program, Los Angeles, CA 90095 USA. Kyoto Univ, Dept Epidemiol & Healthcare Res, Kyoto, Japan. RP Min, LC (reprint author), Univ Calif Los Angeles, Dept Geriatr Med, David Geffen Sch Med, 10945 Conte Ave,Suite 2339 Box 951687, Los Angeles, CA 90095 USA. EM lmin@mednet.ucla.edu FU BHP HRSA HHS [PE-19001]; NIA NIH HHS [AG10415] NR 50 TC 86 Z9 86 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2007 VL 45 IS 6 BP 480 EP 488 DI 10.1097/MLR.0b013e318030fff9 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 176JJ UT WOS:000247080700002 PM 17515774 ER PT J AU Bryson, CL Au, DH Young, B McDonell, MB Fihn, SD AF Bryson, Chris L. Au, David H. Young, Bessie McDonell, Mary B. Fihn, Stephan D. TI A refill adherence algorithm for multiple short intervals to estimate refill compliance (ReComp) SO MEDICAL CARE LA English DT Article DE drug; compliance; adherence; validity; methods; pharmacy ID PHARMACY RECORDS; MEDICATION ADHERENCE; THERAPY; PERSISTENCE; VALIDATION AB Background: There are many measures of refill adherence available, but few have been designed or validated for use with repeated measures designs and short observation periods. Objective: To design a refill-based adherence algorithm suitable for short observation periods, and compare it to 2 reference measures. Methods: A single composite algorithm incorporating information on both medication gaps and oversupply was created. Electronic Veterans Affairs pharmacy data, clinical data, and laboratory data from routine clinical care were used to compare the new measure, ReComp, with standard reference measures of medication gaps (MEDOUT) and adherence or oversupply (MEDSUM) in 3 different repeated measures medication adherence-response analyses. These analyses examined the change in low density lipoprotein (LDL) with simvastatin use, blood pressure with antihypertensive use, and heart rate with P-blocker use for 30- and 90-day intervals. Measures were compared by regression based correlations (R-2 values) and graphical comparisons of average medication adherence-response curves. Results: In each analysis, ReComp yielded a significantly higher R-2 value and more expected adherence-response curve regardless of the length of the observation interval. For the 30-day intervals, the highest correlations were observed in the LDL-simvastatin analysis (ReComp R-2 = 0.231; [95% CI, 0.222-0.239]; MEDSUM R 2 = 0.054; [95% CI, 0.049-0.059]; MEDOUT R 2 = 0.053; [95% CI, 0.048-0.058]). Conclusions: ReComp is better suited to shorter observation intervals with repeated measures than previously used measures. C1 VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev NW Ctr Excellence, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Epidemol Res & Informat Ctr, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Bryson, CL (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Hlth Serv Res & Dev NW Ctr Excellence, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM cbryson@u.washington.edu NR 17 TC 64 Z9 64 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2007 VL 45 IS 6 BP 497 EP 504 DI 10.1097/MLR.0b013e3180329368 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 176JJ UT WOS:000247080700004 PM 17515776 ER PT J AU Carr, PL Palepu, A Szalacha, L Caswell, C Inui, T AF Carr, Phyllis L. Palepu, Anita Szalacha, Laura Caswell, Cheryl Inui, Thomas TI 'Flying below the radar': a qualitative study of minority experience and management of discrimination in academic medicine SO MEDICAL EDUCATION LA English DT Article DE multicentre study [publication type]; humans; prejudice; research, biomedical; minority groups, psychology; academic medical centres, organisation & administration, ethics; ethics, institutional; faculty; medical; ethnic groups, psychology; attitude of health personnel; United States ID FACULTY; CAREER; TIME AB OBJECTIVES This paper aims to give voice to the lived experience of faculty members who have encountered racial or ethnic discrimination in the course of their academic careers. It looks at how they describe the environment for minorities, how they manage discrimination and what institutions and majority-member faculty can do to improve medical academe for minority members. METHODS Qualitative techniques were used for semi-structured, in-depth individual telephone interviews, which were audiotaped, transcribed and analysed by reviewers. Themes expressed by multiple faculty members were studied for patterns of connection and grouped into broader categories. A description of the faculty sample is provided, in which respondents ranked the importance of discrimination in hindering academic advancement and used Likert scales to evaluate effects of discrimination. The sample was drawn from 12 of 24 academic medical centres in the National Faculty Survey and included 18 minority-member faculty staff stratified by gender, rank and degree who had experienced, or possibly experienced, work-related discrimination. RESULTS Minority faculty described the need to be strongly self-reliant, repeatedly prove themselves, develop strong supports and acquire a wide range of academic skills to succeed. Suggested responses to discrimination were to be cautious, level-headed and informed. Confronting discriminatory actions by sitting down with colleagues and raising the level of awareness were important methods of dealing with such situations. CONCLUSIONS Academic medical centres may need to make greater efforts to support minority faculty and improve understanding of the challenges confronting such faculty in order to prevent the loss and/or under-utilisation of important talent. C1 Harvard Univ, Sch Med, Div Gen Internal Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ British Columbia, St Pauls Hosp, Div Gen Internal Med, Vancouver, BC V5Z 1M9, Canada. Brown Univ, Dept Educ, Providence, RI 02912 USA. Survey Res Ctr, New England Res Inst, Watertown, MA USA. Indiana Univ, Sch Med, Regenstrief Inst Hlth Care, Indianapolis, IN 46204 USA. RP Carr, PL (reprint author), Boston Univ, Sch Med, 715 Albany St,L-109, Boston, MA 02118 USA. EM plcarr@bu.edu OI Palepu, Anita/0000-0002-7881-4800 NR 16 TC 29 Z9 29 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0308-0110 J9 MED EDUC JI Med. Educ. PD JUN PY 2007 VL 41 IS 6 BP 601 EP 609 DI 10.1111/j.1365-2923.2007.02771.x PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 169WW UT WOS:000246623800012 PM 17518841 ER PT J AU Meaney, PM Fang, QQ Rubaek, T Demidenko, E Paulsen, KD AF Meaney, Paul M. Fang, Qianqian Rubaek, Tonny Demidenko, Eugene Paulsen, Keith D. TI Log transformation benefits parameter estimation in microwave tomographic imaging SO MEDICAL PHYSICS LA English DT Article DE microwave imaging; parameter estimation; variance stabilizing transformation; residual error analysis; breast imaging; ordinary least squares ID INVERSE SCATTERING; RECONSTRUCTION; SYSTEM; SPECTROSCOPY; REGRESSIONS; EXPERIENCE; TISSUES; PHASE AB Microwave tomographic imaging falls under a broad category of nonlinear parameter estimation methods when a Gauss-Newton iterative reconstruction technique is used. A fundamental requirement in using these approaches is evaluating the appropriateness of the regression model. While there have been numerous investigations of regularization techniques to improve overall image quality, few, if any, studies have explored the underlying statistical properties of the model itself. The ordinary least squares (OLS) approach is used most often, but there are other options such as the weighted least squares (WLS), maximum likelihood (ML), and maximum a posteriori (MAP) that may be more appropriate. In addition, a number of variance stabilizing transformations can be applied to make the inversion intrinsically more linear. In this paper, a statistical analysis is performed of the properties of the residual errors from the reconstructed images utilizing actual measured data and it is demonstrated that the OLS algorithm with a log transformation (OLSlog) is clearly advantageous relative to the more commonly used OLS approach by itself. In addition, several high contrast imaging experiments are performed, which demonstrate that different subsets of data are emphasized in each method and may contribute to the overall image quality differences. (c) 2007 American Association of Physicists in Medicine. C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Tech Univ Denmark, Lyngby, Denmark. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03756 USA. RP Meaney, PM (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. FU NCI NIH HHS [P01-CA80139]; NIBIB NIH HHS [R01-EB001982] NR 44 TC 17 Z9 17 U1 2 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 EI 2473-4209 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2014 EP 2023 DI 10.1118/1.2737264 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600019 PM 17654905 ER PT J AU Trofimov, A Vrancic, C Chan, TCY Sharp, G Bortfeld, T AF Trofimov, A. Vrancic, C. Chan, T. C. Y. Sharp, G. Bortfeld, T. TI Tumor trailing strategy for IMRT in the presence of target motion: Preliminary studies SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Heidelberg, Heidelberg, Germany. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2329 EP 2329 DI 10.1118/1.2760337 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600055 ER PT J AU Mori, S Wolfgang, J Lu, H Choi, NC Chen, G AF Mori, S. Wolfgang, J. Lu, H. Choi, N. C. Chen, G. TI Range fluctuation analysis due to respiratory motion in charged particle lung therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2335 EP 2335 DI 10.1118/1.2760366 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600082 ER PT J AU Court, L Wagar, M Ionascu, T Berbeco, R Chin, L AF Court, L. Wagar, M. Ionascu, T. Berbeco, R. Chin, L. TI Management of dynamic MLCs when treating moving targets SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2336 EP 2336 DI 10.1118/1.2760368 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600084 ER PT J AU Liu, B AF Liu, B. TI Estimating the volume of dense breast tissue using a dual energy technique in digital mammography SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2360 EP 2360 DI 10.1118/1.2760475 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600189 ER PT J AU Ionascu, D Park, S Killoran, J Mamede, M Thomas, S Gerbaudo, V Chin, L Berbeco, R AF Ionascu, D. Park, S. Killoran, J. Mamede, M. Thomas, S. Gerbaudo, V. Chin, L. Berbeco, R. TI Experimental evaluation of motion effects by integration of the 4DCT/4DPET hybrid GE discovery VCT scanner with the CIRS dynamic lung phantom SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Div Nuclear Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2361 EP 2361 DI 10.1118/1.2760477 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600191 ER PT J AU McLaughlin, M Wu, H Mahoui, M Shirato, H Jiang, S AF McLaughlin, M. Wu, H. Mahoui, M. Shirato, H. Jiang, S. TI Correlation analysis between internal and external SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Indiana Univ Purdue Univ, Indianapolis, IN 46202 USA. Hokkaido Univ, Sch Med, Sapporo, Hokkaido, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Shirato, Hiroki/A-7068-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2388 EP 2389 DI 10.1118/1.2760594 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600308 ER PT J AU Riboldi, M Chen, GTY Wolfgang, J Suit, H Baroni, G Paganetti, H Seco, J AF Riboldi, M. Chen, G. T. Y. Wolfgang, J. Suit, H. Baroni, G. Paganetti, H. Seco, J. TI Dosimetric impact of motion mitigation strategies in the irradiation of moving tumors: A 4D Monte Carlo simulation study SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 MIT, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Politecn Milan, I-20133 Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2389 EP 2389 DI 10.1118/1.2760597 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600311 ER PT J AU Spadea, M Riboldi, M Baroni, G Chen, G Sharp, G AF Spadea, M. Riboldi, M. Baroni, G. Chen, G. Sharp, G. TI A feature matching approach for the automatic correlation of internal and external motion in lung tumors SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Spadea, Maria Francesca/I-2468-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2390 EP 2391 DI 10.1118/1.2760603 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600317 ER PT J AU Wu, Z Sharp, G Seco, J Paganetti, H AF Wu, Z. Sharp, G. Seco, J. Paganetti, H. TI The effects of anatomy motion on dose distribution SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2397 EP 2397 DI 10.1118/1.2760629 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600343 ER PT J AU Craft, D Halabi, T Shih, H Bortfeld, T AF Craft, D. Halabi, T. Shih, H. Bortfeld, T. TI A systematic approach to practical multi-criteria IMRT planning SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2412 EP 2412 DI 10.1118/1.2760698 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600409 ER PT J AU Martin, B Bortfeld, T Castanon, D AF Martin, B. Bortfeld, T. Castanon, D. TI Accelerating IMRT optimization by voxel sampling SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Boston Univ, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2413 EP 2414 DI 10.1118/1.2760705 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600416 ER PT J AU Aljarrah, K Niemierko, A Jiang, S AF aljarrah, k. Niemierko, A. Jiang, S. TI Clinical study to evaluate the dose calculation accuracy for IMRT lung patients SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Jordan Univ Sci & Technol, Irbid, Jordan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2425 EP 2425 DI 10.1118/1.2760763 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600466 ER PT J AU Folkert, M Mauceri, T Hollows, M Chen, G AF Folkert, M. Mauceri, T. Hollows, M. Chen, G. TI Clinical field matching using intraoperative 90-Y brachytherapy plaques SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Implant Sci Corp, Wakefield, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2425 EP 2425 DI 10.1118/1.2760760 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600463 ER PT J AU Clasie, B Kooy, H Claereboudt, Y Paganetti, H Flanz, J AF Clasie, B. Kooy, H. Claereboudt, Y. Paganetti, H. Flanz, J. TI Design of a vacuum chamber for a universal proton therapy nozzle SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ion Beam Applicat, Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2432 EP 2432 DI 10.1118/1.2760795 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600496 ER PT J AU Jarlskog, CZ Lee, C Bolch, W Xu, X Paganetti, H AF Jarlskog, C. Zacharatou Lee, C. Bolch, W. Xu, X. Paganetti, H. TI Different methods of organ equivalent dose scoring in Monte Carlo neutron dose calculations SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MD Anderson Canc Ctr, Orlando, FL USA. Univ Florida, Gainesville, FL USA. Rensselaer Polytech Inst, Troy, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2437 EP 2437 DI 10.1118/1.2760816 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600516 ER PT J AU Biggs, P Styczynski, J AF Biggs, P. Styczynski, J. TI Do obliquity factors apply to 30 degrees scattered radiation from megavoltage photon beams? SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. RI STYCZYNSKI, JAN/D-3922-2014 OI STYCZYNSKI, JAN/0000-0002-3158-119X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2438 EP 2438 DI 10.1118/1.2760820 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600520 ER PT J AU Buettner, F Spezi, E Paganetti, H Seco, J AF Buettner, F. Spezi, E. Paganetti, H. Seco, J. TI Dosimetric uncertainties in IMRT QA in plastic phantoms due to CT calibration SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Univ Heidelberg, Heidelberg, Germany. Velindre Hosp, Cardiff, S Glam, Wales. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. RI Spezi, Emiliano/A-8917-2008 OI Spezi, Emiliano/0000-0002-1452-8813 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2442 EP 2442 DI 10.1118/1.2760840 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600540 ER PT J AU Vrancic, C Trofimov, A Chan, T Sharp, G Bortfeld, T AF Vrancic, C. Trofimov, A. Chan, T. Sharp, G. Bortfeld, T. TI Experimental evaluation of a robust optimization method for IMRT of moving targets SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Univ Heidelberg, Heidelberg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2453 EP 2453 DI 10.1118/1.2760885 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600583 ER PT J AU Clasie, B Kooy, H Claereboudt, Y Hubeau, J Paganetti, H Pricels, D Flanz, J AF Clasie, B. Kooy, H. Claereboudt, Y. Hubeau, J. Paganetti, H. Pricels, D. Flanz, J. TI Optimization of the beam width in a universal proton therapy nozzle SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2477 EP 2478 DI 10.1118/1.2760994 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600690 ER PT J AU Paganetti, H Jaekel, O Lomax, A Palmans, H Molina, IQ Sobolevsky, N Vatnitsky, S Capote Noy, R AF Paganetti, H. Jaekel, O. Lomax, A. Palmans, H. Molina, I. Quesada Sobolevsky, N. Vatnitsky, S. Capote Noy, R. TI The IAEA initiative to standardize nuclear data for heavy charged-particle radiotherapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Deutsches Krebsforschungzentrum, Heidelberg, Germany. Paul Scherrer Inst, Villigen, Switzerland. Univ Seville, Seville, Spain. Russian Acad Sci, Moscow, Russia. IAEA, Vienna, Austria. RI Capote Noy, Roberto/M-1245-2014 OI Capote Noy, Roberto/0000-0002-1799-3438 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2495 EP 2495 DI 10.1118/1.2761133 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600767 ER PT J AU Knopf', A Parodi, K Paganetti, H Cascio, E Bonab, A Bortfeld, T AF Knopf', A. Parodi, K. Paganetti, H. Cascio, E. Bonab, A. Bortfeld, T. TI Quantitative assessment of the accuracy of proton beam range verification with PET/CT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. HIT Betriebs GMbH, Heidelberg, Germany. NR 0 TC 1 Z9 2 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2508 EP 2508 DI 10.1118/1.2761186 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600820 ER PT J AU Smith, A Paganetti, H AF Smith, A. Paganetti, H. TI Proton therapy SO MEDICAL PHYSICS LA Danish DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2514 EP 2514 DI 10.1118/1.2761204 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600838 ER PT J AU Boldea, V Sharp, G Jiang, S Sarrut, D AF Boldea, V. Sharp, G. Jiang, S. Sarrut, D. TI Construction of 4D-CT motion model using deformable registration: comparison of eulerian and Lagrangian approaches SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Univ Lyon 2, LIRIS Lab, Lyon, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Leon Berard, F-69373 Lyon, France. CREATIS Lab, Villeurbanne, France. RI Sarrut, David/F-4849-2010 OI Sarrut, David/0000-0002-4854-4141 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2517 EP 2517 DI 10.1118/1.2761218 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600850 ER PT J AU Folkert, M Mori, S Chen, G AF Folkert, M. Mori, S. Chen, G. TI Liquid scintillation-based proton residual range measurement using a dynamic biological lung phantom SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2521 EP 2521 DI 10.1118/1.2761234 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600864 ER PT J AU Lee, E Cha, K Bortfeld, T Deasy, J AF Lee, E. Cha, K. Bortfeld, T. Deasy, J. TI Robust optimization to accommodate effects of systematic treatment uncertainties SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2523 EP 2524 DI 10.1118/1.2761247 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600876 ER PT J AU Unkelbach, J Chan, TCY Bortfeld, T AF Unkelbach, J. Chan, T. C. Y. Bortfeld, T. TI Reducing the sensitivity of IMPT treatment plans to setup errors and range variations SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2523 EP 2523 DI 10.1118/1.2761244 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600874 ER PT J AU Ionascu, D Park, S Killoran, J Allen, A Berbeco, R AF Ionascu, D. Park, S. Killoran, J. Allen, A. Berbeco, R. TI Marker-less intra-fraction position verification of lung tumors with an EPID in cine mode SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2528 EP 2528 DI 10.1118/1.2761268 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600893 ER PT J AU Tang, X Sharp, G Jiang, S AF Tang, X. Sharp, G. Jiang, S. TI Fluoroscopic tracking of multiple implanted fiducial markers using multiple object tracking algorithm SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2529 EP 2529 DI 10.1118/1.2761271 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600896 ER PT J AU Chan, TCY Trofimov, A Vrancic, C Tsitsiklis, JN Bortfeld, T AF Chan, T. C. Y. Trofimov, A. Vrancic, C. Tsitsiklis, J. N. Bortfeld, T. TI Application of robust optimization in lung cancer treatment SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Heidelberg, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2535 EP 2535 DI 10.1118/1.2761296 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600920 ER PT J AU Sharp, G Lu, H Trofimov, A Tang, X Jiang, S Turcotte, J Gierga, D Chen, G Hong, T AF Sharp, G. Lu, H. Trofimov, A. Tang, X. Jiang, S. Turcotte, J. Gierga, D. Chen, G. Hong, T. TI Assessing residual motion for gated proton-beam radiotherapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2545 EP 2545 DI 10.1118/1.2761332 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600953 ER PT J AU Seco, J Gianolini, S Sharp, G Wu, Z Giergal, D Buettner, F Paganetti, H AF Seco, J. Gianolini, S. Sharp, G. Wu, Z. Giergal, D. Buettner, F. Paganetti, H. TI Image guided 4D Monte Carlo study of the dosimetric effects of intra/inter fraction motion in lung tumors SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. TomoTherapy, Diegem, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2546 EP 2546 DI 10.1118/1.2761336 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600957 ER PT J AU Bortfeld, T Chen, G Paganetti, H Unkelbach, J Engelsman, M AF Bortfeld, T. Chen, G. Paganetti, H. Unkelbach, J. Engelsman, M. TI The good and the not-so-good of the finite proton range SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2552 EP 2553 DI 10.1118/1.2761362 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600983 ER PT J AU Paganetti, H AF Paganetti, H. TI Should we worry about neutrons? SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2553 EP 2553 DI 10.1118/1.2761363 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600984 ER PT J AU Safai, S Bortfeld, T Engelsman, M AF Safai, S. Bortfeld, T. Engelsman, M. TI Comparison between the lateral penumbra of a double scattering proton beam and the lateral penumbra of a scanning beam SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2558 EP 2558 DI 10.1118/1.2761382 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601003 ER PT J AU Wu, H Zhao, Q Shirato, H Jiang, S AF Wu, H. Zhao, Q. Shirato, H. Jiang, S. TI Correlating lung tumor motion patterns with its geometrical location SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Indiana Univ Purdue Univ, Indianapolis, IN 46202 USA. Purdue Univ, W Lafayette, IN 47907 USA. Hokkaido Univ, Sch Med, Sapporo, Hokkaido 060, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Shirato, Hiroki/A-7068-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2573 EP 2574 DI 10.1118/1.2761448 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601068 ER PT J AU Bortfeld, T Trofimov, A Unkelbach, J Chan, TCY Martin, B AF Bortfeld, T. Trofimov, A. Unkelbach, J. Chan, T. C. Y. Martin, B. TI Patient motion: Adaptive RT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2584 EP 2584 DI 10.1118/1.2761485 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601102 ER PT J AU Paganetti, H AF Paganetti, H. TI Differences in predicted beam range, lateral scatter and absolute dose between proton monte carlo and pencil-beam dose calculation considering single fields and full plans for head and neck tumors SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2589 EP 2589 DI 10.1118/1.2761508 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601122 ER PT J AU Jarlskog, CZ Lee, C Bolch, W Xu, X Paganetti, H AF Jarlskog, C. Zacharatou Lee, C. Bolch, W. Xu, X. Paganetti, H. TI Simulation of neutron dose exposure for pediatric proton therapy patients using whole-body age-dependent voxel phantoms SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MD Anderson Canc Ctr, Orlando, FL USA. Univ Florida, Gainesville, FL USA. Rensselaer Polytech Inst, Troy, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2590 EP 2590 DI 10.1118/1.2761512 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601126 ER PT J AU Chen, Y Liu, B O'Connor, M Didier, C Glick, S AF Chen, Y. Liu, B. O'Connor, M. Didier, C. Glick, S. TI Scatter measurements and simulations in x-ray cone beam CT breast imaging SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Univ Massachusetts, Sch Med, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Lowell, MA USA. RI Chen, Yu/E-3788-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2606 EP 2606 DI 10.1118/1.2761578 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601188 ER PT J AU Roberson, D Seco, J Trofimov, A Paganetti, H AF Roberson, D. Seco, J. Trofimov, A. Paganetti, H. TI Breathing interplay effects during proton beam spot scanning: Simulation and statistical analysis SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Brigham Young Univ, Provo, UT 84602 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2627 EP 2627 DI 10.1118/1.2761665 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601272 ER PT J AU Singh, H Kandasamy, N Folkert, M Sharp, G AF Singh, H. Kandasamy, N. Folkert, M. Sharp, G. TI Streaming architectures for cone-beam CT image reconstruction and deformable registration SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Drexel Univ, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2634 EP 2634 DI 10.1118/1.2761696 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601302 ER PT J AU Xiang, H Cormack, R Tishler, R Maxion, T Makrigiorgos, M Chin, L Court, L AF Xiang, H. Cormack, R. Tishler, R. Maxion, T. Makrigiorgos, M. Chin, L. Court, L. TI Deformatile registration of KV/MV projection images for quantifying patient setup offsets and anatomical deformations in head and neck IMRT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham Womens Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2638 EP 2638 DI 10.1118/1.2761710 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601316 ER PT J AU Chan, HP Wu, Y Sahiner, B Zhang, Y Moore, RH Kopans, DB Hadjiiski, L Helvie, MA AF Chan, H. P. Wu, Y. Sahiner, B. Zhang, Y. Moore, R. H. Kopans, D. B. Hadjiiski, L. Helvie, M. A. TI Digital breast tomosynthesis mammography: Computerized classification of malignant and benign masses SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2645 EP 2645 DI 10.1118/1.2761739 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601345 ER PT J AU Li, X Liu, B AF Li, X. Liu, B. TI A high precision geometry calibration method for digital tomosynthesis systems SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2645 EP 2645 DI 10.1118/1.2761738 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601344 ER PT J AU Stefano, GB Bianchi, E Guarna, M Fricchione, GL Zhu, W Cadet, P Mantione, KJ Casares, FM Kream, RM Esch, T AF Stefano, George B. Bianchi, Enrica Guarna, Massimo Fricchione, Gregory L. Zhu, Wei Cadet, Patrick Mantione, Kirk J. Casares, Federico M. Kream, Richard M. Esch, Tobias TI Nicotine, alcohol and cocaine coupling to reward processes via endogenous morphine signaling: The dopamine-morphine hypothesis SO MEDICAL SCIENCE MONITOR LA English DT Review DE pleasure; reward; addiction; motivation; nicotine; ethanol; dopamine; morphine ID NITRIC-OXIDE RELEASE; WHITE BLOOD-CELLS; MYTILUS-EDULIS BIVALVIA; VENTRAL TEGMENTAL AREA; OPIATE-LIKE SUBSTANCES; NUCLEUS-ACCUMBENS; IMMUNE-RESPONSE; ACETYLCHOLINE-RECEPTORS; GANGLIONIC MORPHINE; CIGARETTE-SMOKE AB Pleasure is described as a state or feeling of happiness and satisfaction resulting from an experience that one enjoys. We examine the neurobiological factors underlying reward processes and pleasure phenomena. With regard to possible negative effects of pleasure, we focus on addiction and motivational toxicity. Pleasure can serve cognition, productivity and health, but simultaneously promotes addiction and other negative behaviors. It is a complex neurobiological phenomenon, relying on reward circuitry or limbic activity. These processes involve dopaminergic signaling. Moreover, nicotine, cocaine and alcohol appear to exert their pleasure providing action via endogenous morphinergic mechanisms. Natural rewarding activities are necessary for survival and appetitive motivation, usually governing beneficial biological behaviors like eating, sex arid reproduction. Social contacts can further facilitate the positive effects exerted by pleasurable experiences. However, artificial stimulants can be detrimental, since flexibility and normal control of behavior are deteriorated. Additionally, addictive drugs are capable of directly acting on reward pathways, now, in part, via endogenous morphine processes. C1 SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. Univ Siena, Dept Neurosci, I-53100 Siena, Italy. Univ Siena, Dept Biomed Sci, I-53100 Siena, Italy. Massachusetts Gen Hosp, Div Psychiat & Med, Boston, MA 02114 USA. SUNY Hlth Sci Ctr, Dept Biochem, Brooklyn, NY 11203 USA. Coburg Univ Appl Sci, Div Integrat Hlth Promot, Coburg, Germany. Inst Integrat Med & Hlth Res, Potsdam, Germany. RP Stefano, GB (reprint author), SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. EM gstefano@sunynri.org RI Esch, Tobias/J-3812-2013 OI Esch, Tobias/0000-0001-5176-4367 FU NIDA NIH HHS [DA009010]; NIMH NIH HHS [MH047392] NR 197 TC 30 Z9 30 U1 2 U2 8 PU INT SCIENTIFIC LITERATURE, INC PI ALBERTSON PA 1125 WILLIS AVE, ALBERTSON, NY 11507 USA SN 1234-1010 J9 MED SCI MONITOR JI Med. Sci. Monitor PD JUN PY 2007 VL 13 IS 6 BP RA91 EP RA102 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 182CG UT WOS:000247482100016 PM 17534245 ER PT J AU Pumbwe, L Chang, A Smith, RL Wexler, HM AF Pumbwe, Lilian Chang, Abraham Smith, Rachel L. Wexler, Hannah M. TI BmeRABC5 is a multidrug efflux system that can confer metronidazole resistance in Bacteroides fragilis SO MICROBIAL DRUG RESISTANCE-MECHANISMS EPIDEMIOLOGY AND DISEASE LA English DT Article ID TRANSCRIPTIONAL REPRESSOR; PUMP; SUSCEPTIBILITY; STRAINS AB The RND-family efflux pump gene bmeB5 was previously shown to be overexpressed in metronidazole-resistant laboratory mutants of Bacteroides fragilis. In the present study, we characterized the bmeABC5 genes and an upstream putative TetR-family regulator gene (bmeR5). bmeR5 (645 bp) was located 51 bp upstream of bmeA5 and encoded a 24.9-kDa protein. Deletant strains lacking bmeB5 or bmeR5 were constructed from a wild-type B. fragilis strain ADB77. Strain antimicrobial susceptibility was determined and gene expression was quantified. bmeR5 was overexpressed in Escherichia coli using a 6 x-His tag system; BmeR5-HiS(6) was isolated from inclusion bodies and its binding to bmeABC5 promoter regions was determined. BmeR5-HiS(6) bound specifically to the bmeR5-bmeC5 intergenic region (IT1). Deletion of bmeR5 (ADB77 Delta bmeR5) resulted in a significant (p < 0.05) increase in expression of bmeA5, bmeB5, and bmeC5, and > two-fold increase in minimum inhibitory concentrations (MICs) of ampicillin, cefoxitin, cefoperazone, ciprofloxacin, imipenem, metronidazole, ethidium bromide, and sodium dodecyl sulfate (SDS). MICs were reduced by the efflux pump inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP). The MICs of ampicillin, cefoperazone, metronidazole, and SDS were reduced by approximately two-fold in ADB77 Delta bmeB5. A multidrug (metronidazole)-resistant, nim-negative B. fragilis clinical isolate overexpressed bmeABC5 genes, had a G -> T point mutation in IT1, and significantly reduced binding to BmeR5-HiS(6). These data demonstrate that BmeR5 is a local repressor of bmeABC5 expression and that mutations in IT1 can lead to a derepression and resistance to multiple antimicrobial agents, including metronidazole. C1 Wadsworth Anaerobe Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Pumbwe, L (reprint author), Wadsworth Anaerobe Lab, Bldg 304,Room E3-226,GLAVAHCS 691-151J, Los Angeles, CA 90073 USA. EM lilskil@ucla.edu NR 15 TC 19 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-6294 J9 MICROB DRUG RESIST JI Microb. Drug Resist.-Mechan. Epidemiol. Dis. PD SUM PY 2007 VL 13 IS 2 BP 96 EP 101 DI 10.1089/mdr.2007.719 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 194SD UT WOS:000248363200004 PM 17650960 ER PT J AU Mooij, MJ Drenkard, E Llamas, MA Broucke-Grauls, CMJEV Savelkoul, PHM Ausubel, FM Bitter, W AF Mooij, Marlies J. Drenkard, Eliana Llamas, Maria A. Broucke-Grauls, Christina M. J. E. Vanden Savelkoul, Paul H. M. Ausubel, Frederick M. Bitter, Wilbert TI Characterization of the integrated filamentous phage Pf5 and its involvement in small-colony formation SO MICROBIOLOGY-SGM LA English DT Article ID PSEUDOMONAS-AERUGINOSA BIOFILMS; PHENOTYPIC VARIATION; ESCHERICHIA-COLI; VARIANTS; DNA; BACTERIOPHAGE; EXPRESSION; SEQUENCE; REGION; MU AB Bacteriophages play an important role in bacterial virulence and phenotypic variation. It has been shown that filamentous bacteriophage Pf4 of Pseudomonas aeruginosa strain PAO1 mediates the formation of small-colony variants (SCVs) in biofilms. This morphology type is associated with parameters of poor lung function in cystic fibrosis patients, and SCVs are often more resistant to antibiotics than wild-type cells. P. aeruginosa strain PA14 also contains a Pf1-like filamentous prophage, which is designated Pf5, and is highly homologous to Pf4. Since P. aeruginosa PA14 produces SCVs very efficiently in biofilms grown in static cultures, the role of Pf5 in SCV formation under these conditions was investigated. The presence of the Pf5 replicative form in total DNA from SCVs and wild-type cells was detected, but it was not possible to detect the Pf5 major coat protein by immunoblot analysis in PA14 SCV cultures. This suggests that the Pf5 filamentous phage is not present at high densities in the PA14 SCVs. Consistent with these results, we were unable to detect coaB expression in SCV cultures and SCV colonies. The SCV variants formed under static conditions were not linked to Pf5 phage activity, since Pf5 insertion mutants with decreased or no production of the Pf5 RF produced SCVs as efficiently as the wild-type strain. Finally, analysis of 48 clinical P. aeruginosa isolates showed no association between the presence of Pf1-like filamentous phages and the ability to form SCVs under static conditions; this suggests that filamentous phages are generally not involved in the emergence of P. aeruginosa SCVs. C1 VU Med Ctr, Dept Med Microbiol & Infect Control, NL-1081 BT Amsterdam, Netherlands. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Bitter, W (reprint author), VU Med Ctr, Dept Med Microbiol & Infect Control, van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM w.bitter@vumc.nl RI Llamas, Maria A/M-1669-2014 OI Llamas, Maria A/0000-0002-9499-0492 NR 25 TC 19 Z9 21 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JUN PY 2007 VL 153 BP 1790 EP 1798 DI 10.1099/mic.0.2006/003533-0 PN 6 PG 9 WC Microbiology SC Microbiology GA 179QM UT WOS:000247304900011 PM 17526836 ER PT J AU Zen, Y Adsay, NV Bardadin, K Colombari, R Ferrell, L Haga, H Hong, SM Hytiroglou, P Kloppel, G Lauwers, GY van Leeuwen, DJ Notohara, K Oshima, K Quaglia, A Sasaki, M Sessa, F Suriawinata, A Tsui, W Atomi, Y Nakanuma, Y AF Zen, Yoh Adsay, N. Volkan Bardadin, Krystof Colombari, Romano Ferrell, Linda Haga, Hironori Hong, Seung-Mo Hytiroglou, Prodromos Kloppel, Gunter Lauwers, Gregory Y. van Leeuwen, Dirk J. Notohara, Kenji Oshima, Kiyoko Quaglia, Alberto Sasaki, Motoko Sessa, Fausto Suriawinata, Arief Tsui, Wilson Atomi, Yutaka Nakanuma, Yasuni TI Biliary intraepithelial neoplasia: an international interobserver agreement study and proposal for diagnostic criteria SO MODERN PATHOLOGY LA English DT Article DE biliary dysplasia; BillN; intrahepatic cholangiocarcinoma; cholangiocarcinoma; bile duct ID INTRADUCTAL PAPILLARY NEOPLASM; PRIMARY SCLEROSING CHOLANGITIS; BILE-DUCT; MUCINOUS NEOPLASMS; INTRAHEPATIC CHOLANGIOCARCINOMA; PATHOLOGICAL FEATURES; EXPRESSION; CLASSIFICATION; DYSPLASIA; CARCINOMA AB Cholangiocarcinoma of the intrahepatic and extrahepatic bile ducts develops through a multistep histopathologic sequence. Premalignant or non-invasive neoplastic lesions of bile ducts have been historically called biliary dysplasia or atypical biliary epithelium. To this date, no standard terminology or classification system has been offered for these lesions. In 2005, a conceptual framework and diagnostic criteria for biliary intraepithelial neoplasia (BilIN) were proposed using the livers of patients with hepatolithiasis. We report herein an international interobserver agreement study on the diagnosis of biliary non-invasive neoplastic lesions with the goal to obtain a consensus on the terminology and grading. Seventeen pathologists from the United States, Europe and Asia participated in this study. They shared a digital file containing histological pictures of 30 foci of non-invasive neoplastic lesions selected from the biliary system of patients suffering from primary sclerosing cholangitis, choledochal cyst or hepatolithiasis. In the criteria, we proposed in 2005, BilIN was classified into three categories based on the degree of atypia: BilIN-1, BilIN-2 and BilIN-3. In this study, consensus was reached for the terminology of BilIN and the three-grade classification system. Interobserver agreement on the diagnosis was moderate (kappa-value = 0.45). On the basis of the suggestions and opinions obtained from the 17 participants, the original criteria for BilIN were revised. We now propose a new consensus classification of BilIN that may assist in allowing a more uniform terminology for the diagnosis of biliary non-invasive neoplastic lesions. This classification should help to advance clinical and research applications. C1 Kanazawa Univ, Grad Sch Med, Dept Human Pathol, Kanazawa, Ishikawa 9208640, Japan. Wayne State Univ, Harper Hosp, Dept Pathol, Detroit, MI USA. Med Ctr Postgrad Educ, Dept Pathol, Warsaw, Poland. G Fracastoro City Hosp, Dept Pathol, Verona, Italy. Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. Kyoto Univ Hosp, Anat Pathol Lab, Kyoto 606, Japan. Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA USA. Aristotle Univ Thessaloniki, Sch Med, Dept Pathol, Thessaloniki, Greece. Univ Kiel, Dept Pathol, D-2300 Kiel, Germany. Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Sect Gastroenterol Hepatol & Pathol, Lebanon, NH 03766 USA. Kurashiki Cent Hosp, Dept Pathol, Kurashiki, Okayama, Japan. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. Kings Coll London, Inst Liver Studies, London WC2R 2LS, England. Univ Insubria, Dept Human Morphol, Varese, Italy. Caritas Med Ctr, Dept Pathol, Kowloon, Hong Kong, Peoples R China. Kyorin Univ, Sch Med, Dept Surg, Tokyo, Japan. RP Nakanuma, Y (reprint author), Kanazawa Univ, Grad Sch Med, Dept Human Pathol, 13-1 Takaramachi, Kanazawa, Ishikawa 9208640, Japan. EM pbcpsc@kenroku.kanazawa-u.ac.jp RI Sasaki, Motoko/K-5913-2015; OI Sasaki, Motoko/0000-0003-2514-760X; Hong, Seung-Mo/0000-0002-8888-6007 NR 30 TC 111 Z9 117 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUN PY 2007 VL 20 IS 6 BP 701 EP 709 DI 10.1038/modpathol.3800788 PG 9 WC Pathology SC Pathology GA 170TY UT WOS:000246689100012 PM 17431410 ER PT J AU Gao, JG Maison, SF Wu, XD Hirose, K Jones, SM Bayazitov, I Tian, Y Mittleman, G Matthews, DB Zakharenko, SS Liberman, MC Zuo, J AF Gao, Jiangang Maison, Stephane F. Wu, Xudong Hirose, Keiko Jones, Sherri M. Bayazitov, Ildar Tian, Yong Mittleman, Guy Matthews, Douglas B. Zakharenko, Stanislav S. Liberman, M. Charles Zuo, Jian TI Orphan glutamate receptor delta 1 subunit required for high-frequency hearing SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID OUTER HAIR-CELLS; GLUTAMATE-RECEPTOR; INNER-EAR; POTASSIUM CHANNEL; STRIA VASCULARIS; GENE-EXPRESSION; ACOUSTIC INJURY; MOUSE COCHLEA; MICE; DEAFNESS AB The function of the orphan glutamate receptor delta subunits (GluR delta 1 and GluR delta 2) remains unclear. GluR delta 2 is expressed exclusively in the Purkinje cells of the cerebellum, and GluR delta 1 is prominently expressed in inner ear hair cells and neurons of the hippocampus. We found that mice lacking the GluR delta 1 protein displayed significant cochlear threshold shifts for frequencies of >16 kHz. These deficits correlated with a substantial loss of type IV spiral ligament fibrocytes and a significant reduction of endolymphatic potential in high-frequency cochlear regions. Vulnerability to acoustic injury was significantly enhanced; however, the efferent innervation of hair cells and the classic efferent inhibition of outer hair cells were unaffected. Hippocampal and vestibular morphology and function were normal. Our findings show that the orphan GluR delta 1 plays an essential role in high-frequency hearing and ionic homeostasis in the basal cochlea, and the locus encoding GluR delta 1 represents a candidate gene for congenital or acquired high-frequency hearing loss in humans. C1 St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Otolaryngol, Cleveland, OH 44195 USA. E Carolina Univ, Dept Commun Sci & Disorders, Greenville, NC USA. Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. RP Zuo, J (reprint author), St Jude Childrens Hosp, Dept Dev Neurobiol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM jian.zuo@stjude.org RI Zakharenko, Stanislav/D-3287-2013 OI Zakharenko, Stanislav/0000-0001-8115-202X FU NCI NIH HHS [CA21765, P30 CA021765]; NIDCD NIH HHS [DC06471, DC0188, DC04477, DC04761, DC05168, DC05761, F31 DC005761, F32 DC000188, K08 DC005761, P30 DC005209, P30 DC05209, R01 DC000188, R01 DC000188-24, R01 DC000188-25, R01 DC000188-26, R01 DC000188-27, R01 DC006443, R01 DC006443-02, R01 DC006471, R21 DC005168] NR 48 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2007 VL 27 IS 12 BP 4500 EP 4512 DI 10.1128/MCB.02051-06 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 177JS UT WOS:000247150000027 PM 17438141 ER PT J AU Kiziltepe, T Hideshima, T Catley, L Raje, N Yasui, H Shiraishi, N Okawa, Y Ikeda, H Vallet, S Pozzi, S Ishitsuka, K Ocio, EM Chauhan, D Anderson, KC AF Kiziltepe, Tanyel Hideshima, Teru Catley, Laurence Raje, Noopur Yasui, Hiroshi Shiraishi, Norihiko Okawa, Yutaka Ikeda, Hiroshi Vallet, Sonia Pozzi, Samantha Ishitsuka, Kenji Ocio, Enrique M. Chauhan, Dharminder Anderson, Kenneth C. TI 5-Azacytidine, a DNA methyltransferase inhibitor, induces ATR-mediated DNA double-strand break responses, apoptosis, and synergistic cytotoxicity with doxorubicin and bortezomib against multiple myeloma cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID OVERCOMES DRUG-RESISTANCE; HEMATOLOGIC MALIGNANCIES; MOLECULAR-MECHANISMS; GROWTH-FACTOR; RADIOSENSITIZING AGENT; DAMAGE CHECKPOINTS; REPLICATION FORKS; HISTONE H2AX; SOLID TUMORS; CAM-DR AB In this study, we investigated the cytotoxicity of 5-azacytidine, a DNA methyltransferase inhibitor, against multiple myeloma (MM) cells, and characterized DNA damage-related mechanisms of cell death. 5-Azacytidine showed significant cytotoxicity against both conventional therapy-sensitive and therapy-resistant MM cell lines, as well as multidrug-resistant patient-derived MM cells, with IC50 of similar to 0.8-3 mu mol/L. Conversely, 5-azacytidine was not cytotoxic to peripheral blood mononuclear cells or patient-derived bone marrow stromal cells (BMSC) at these doses. Importantly, 5-azacytidine overcame the survival and growth advantages conferred by exogenous interleukin-6 (IL-6), insulin-like growth factor-I (IGF-I), or by adherence of MM cells to BMSCs. 5-Azacytidine treatment induced DNA double-strand break (DSB) responses, as evidenced by H2AX, Chk2, and p53 phosphorylations, and apoptosis of MM cells. 5-Azacytidine-induced apoptosis was both caspase dependent and independent, with caspase 8 and caspase 9 cleavage; Mcl-1 cleavage; Bax, Puma, and Noxa up-regulation; as well as release of AIF and EndoG from the mitochondria. Finally, we show that 5-azacytidine-induced DNA DSB responses were mediated predominantly by ATR, and that doxorubicin, as well as bortezomib, synergistically enhanced 5-azacytidine-induced MM cell death. Taken together, these data provide the preclinical rationale for the clinical evaluation of 5-azacytidine, alone and in combination with doxorubicin and bortezomib, to improve patient outcome in MM. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM tanyel_kiziltepe@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013; Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 FU NCI NIH HHS [P0-1 CA78373, P50 CA100707]; PHS HHS [R0-1 A50947] NR 77 TC 75 Z9 77 U1 4 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUN PY 2007 VL 6 IS 6 BP 1718 EP 1727 DI 10.1158/1535-7163.MCT-07-0010 PG 10 WC Oncology SC Oncology GA 181LS UT WOS:000247438800005 PM 17575103 ER PT J AU Duran-Pinedo, AE Nishikawa, K Duncan, MJ AF Duran-Pinedo, Ana E. Nishikawa, Kiyoshi Duncan, Margaret J. TI The RprY response regulator of Porphyromonas gingivalis (vo 64, pg 1061, 2007) SO MOLECULAR MICROBIOLOGY LA English DT Correction C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Aichi Gakuin Univ, Sch Dent, Dept Microbiol, Nagoya, Aichi 4648650, Japan. RP Duran-Pinedo, AE (reprint author), Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUN PY 2007 VL 64 IS 5 BP 1416 EP 1416 DI 10.1111/j.1365-2958.2007.05763.x PG 1 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 177TO UT WOS:000247175600020 ER PT J AU Hazra, S Batra, RK Tai, HH Sharma, S Cui, XY Dubinett, SM AF Hazra, Saswati Batra, Raj K. Tai, Hsin H. Sharma, Sherven Cui, Xiaoyan Dubinett, Steven M. TI Pioglitazone and rosiglitazone decrease prostaglandin E-2 in non-small-cell lung cancer cells by up-regulating 15-hydroxyprostaglandin dehydrogenase SO MOLECULAR PHARMACOLOGY LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; CYCLOOXYGENASE-2 EXPRESSION; COLORECTAL-CANCER; COX-2 INHIBITION; TUMOR-SUPPRESSOR; GENE-EXPRESSION; THIAZOLIDINEDIONE; INFLAMMATION; CARCINOMA; PULMONARY AB Lung cancer cells elaborate the immunosuppressive and anti-apoptotic mediator prostaglandin E 2 (PGE 2), a product of cyclooxygenase-2 (COX-2) enzyme activity. Because peroxisome proliferator-activated receptor (PPAR) gamma ligands, such as thiazolidinediones (TZDs), inhibit lung cancer cell growth, we examined the effect of the TZDs pioglitazone and rosiglitazone on PGE 2 levels in non -small-cell lung cancer (NSCLC) A427 and A549 cells. Both TZDs inhibited PGE 2 production in NSCLC cells via a COX-2 independent pathway. To define the mechanism underlying COX-2 independent suppression of PGE 2 production, we focused on other enzymes responsible for the synthesis and degradation of PGE (2). The expression of none of the three prostaglandin synthases (microsomal PGES1, PGES2 and cystosolic PGES) was down-regulated by the TZDs. It is noteworthy that 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme that produces biologically inactive 15-ketoprostaglandins from active PGE 2, was induced by TZDs. The TZD-mediated suppression of PGE 2 concentration was significantly inhibited by small interfering RNA to 15-PGDH. Studies using dominant-negative PPAR gamma overexpression or 2-chloro-5-nitrobenzanilide (GW9662; a PPAR gamma antagonist) revealed that the suppressive effect of the TZDs on PGE 2 is PPAR gamma-independent. Together, these findings indicate that it is possible to use a clinically available pharmacological intervention to suppress tumor-derived PGE 2 by enhancing catabolism rather than blocking synthesis. C1 Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, UCLA Lung Canc Res Program, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY USA. RP Hazra, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, UCLA Lung Canc Res Program, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM shazra@mednet.ucla.edu OI Batra, Raj K./0000-0002-1126-543X FU NCI NIH HHS [R01-CA111851, P50-CA90388] NR 38 TC 58 Z9 59 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 2007 VL 71 IS 6 BP 1715 EP 1720 DI 10.1124/mol.106.033357 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 174YT UT WOS:000246979500029 PM 17412838 ER PT J AU Knickerbocker, T Chen, JR Thadhani, R MacBeath, G AF Knickerbocker, Tanya Chen, Jiunn R. Thadhani, Ravi MacBeath, Gavin TI An integrated approach to prognosis using protein microarrays and nonparametric methods SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE dialysis; end-stage renal disease (ESRD); non-parametric regression; prognosis; protein microarray ID CHRONIC-HEMODIALYSIS PATIENTS; CD4+ T-CELLS; ADHESION MOLECULES; DIALYSIS PATIENTS; CAROTID ATHEROSCLEROSIS; INFLAMMATION; EXPRESSION; SURVIVAL; MORTALITY; INFECTION AB Over the past several years, multivariate approaches have been developed that address the problem of disease diagnosis. Here, we report an integrated approach to the problem of prognosis that uses protein microarrays to measure a focused set of molecular markers and non-parametric methods to reveal non-linear relationships among these markers, clinical variables, and patient outcome. As proof-of-concept, we applied our approach to the prediction of early mortality in patients initiating kidney dialysis. We found that molecular markers are not uniformly prognostic, but instead vary in their value depending on a combination of clinical variables. This may explain why reports in this area aiming to identify prognostic markers, without taking into account clinical variables, are either conflicting or show that markers have marginal prognostic value. Just as treatments are now being tailored to specific subsets of patients, our results show that prognosis can also benefit from a 'personalized' approach. C1 Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP MacBeath, G (reprint author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA. EM macbeath@chemistry.harvard.edu FU NIDDK NIH HHS [DK068465, DK071674, R21 DK068465, R21 DK071674] NR 34 TC 19 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD JUN PY 2007 VL 3 AR 123 DI 10.1038/msb4100167 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 188GL UT WOS:000247907700009 PM 17593911 ER PT J AU Dupuy, D Bertin, N Hidalgo, CA Venkatesan, K Tu, D Lee, D Rosenberg, J Svrzikapa, N Blanc, A Carnec, A Carvunis, AR Pulak, R Shingles, J Reece-Hoyes, J Hunt-Newbury, R Viveiros, R Mohler, WA Tasan, M Roth, FP Le Peuch, C Hope, IA Johnsen, R Moerman, DG Barabasi, AL Baillie, D Vidal, M AF Dupuy, Denis Bertin, Nicolas Hidalgo, Cesar A. Venkatesan, Kavitha Tu, Domena Lee, David Rosenberg, Jennifer Svrzikapa, Nenad Blanc, Aurelie Carnec, Alain Carvunis, Anne-Ruxandra Pulak, Rock Shingles, Jane Reece-Hoyes, John Hunt-Newbury, Rebecca Viveiros, Ryan Mohler, William A. Tasan, Murat Roth, Frederick P. Le Peuch, Christian Hope, Ian A. Johnsen, Robert Moerman, Donald G. Barabasi, Albert-Laszlo Baillie, David Vidal, Marc TI Genome-scale analysis of in vivo spatiotemporal promoter activity in Caenorhabditis elegans SO NATURE BIOTECHNOLOGY LA English DT Article ID EMBRYONIC CELL LINEAGES; C-ELEGANS; GENE-EXPRESSION; UNC-52 TRANSCRIPTS; NETWORK; PROTEIN; RNA; NEMATODE; HERMAPHRODITE; MAP AB Differential regulation of gene expression is essential for cell fate specification in metazoans. Characterizing the transcriptional activity of gene promoters, in time and in space, is therefore a critical step toward understanding complex biological systems. Here we present an in vivo spatiotemporal analysis for similar to B900 predicted C. elegans promoters (similar to 5% of the predicted protein-coding genes), each driving the expression of green fluorescent protein (GFP). Using a flow-cytometer adapted for nematode profiling, we generated 'chronograms', two-dimensional representations of fluorescence intensity along the body axis and throughout development from early larvae to adults. Automated comparison and clustering of the obtained in vivo expression patterns show that genes coexpressed in space and time tend to belong to common functional categories. Moreover, integration of this data set with C. elegans protein-protein interactome data sets enables prediction of anatomical and temporal interaction territories between protein partners. C1 Harvard Univ, Sch Med, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. CNRS, Ctr Rech Biochim Macromol, FRE 2593, F-34293 Montpellier 5, France. Univ Notre Dame, Dept Phys, Ctr Complex Network Res, Notre Dame, IN 46556 USA. Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. Union Biometr, Holliston, MA 01746 USA. Univ Leeds, Inst Integrat & Comparat Biol, Leeds LS2 9JT, W Yorkshire, England. Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada. Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Ctr Cell Anal & Modeling, Farmington, CT 06030 USA. Harvard Univ, Sch Med, Ctr Canc Syst Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Vidal, M (reprint author), Harvard Univ, Sch Med, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM alb@nd.edu; baillie@sfu.ca; marc_vidal@dfci.harvard.edu RI Reece-Hoyes, John/B-2321-2008; Bertin, Nicolas/C-3025-2008; Hidalgo, Cesar/B-5155-2009; Roth, Frederick/H-6308-2011; Dupuy, Denis/M-7299-2014; OI Carvunis, Anne-Ruxandra/0000-0002-6474-6413; Dupuy, Denis/0000-0002-4781-5595; Bertin, Nicolas/0000-0002-9835-9606; , /0000-0002-6031-5982; Roth, Frederick/0000-0002-6628-649X FU NCI NIH HHS [1 P20 CA11300-01, 4 R33 CA097516-02]; NHGRI NIH HHS [HG003224, HG004098]; NICHD NIH HHS [HD43156] NR 42 TC 173 Z9 180 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 2007 VL 25 IS 6 BP 663 EP 668 DI 10.1038/nbt1305 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 176IF UT WOS:000247077500023 PM 17486083 ER PT J AU Dickler, A Khan, AJ AF Dickler, Adam Khan, Atif J. TI Accelerated partial breast irradiation using the MammoSite (R) device SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material ID BRACHYTHERAPY; APPLICATOR; EXPERIENCE; TOXICITY; THERAPY; CANCER; SYSTEM C1 Rush Univ, Med Ctr, Dept Radiat Oncol, Chicago, IL 60612 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Ctr, Boston, MA 02115 USA. RP Dickler, A (reprint author), Rush Univ, Med Ctr, Dept Radiat Oncol, 1653 W Congress Pkwy, Chicago, IL 60612 USA. EM atd22_99@yahoo.com NR 10 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JUN PY 2007 VL 4 IS 6 BP 324 EP 325 DI 10.1038/ncponc0838 PG 2 WC Oncology SC Oncology GA 171GY UT WOS:000246725100002 PM 17534388 ER PT J AU Altfeld, M Goulder, P AF Altfeld, Marcus Goulder, Philip TI 'Unleashed' natural killers hinder HIV SO NATURE GENETICS LA English DT Editorial Material ID IMMUNOGLOBULIN-LIKE RECEPTORS; NK CELLS; CUTTING EDGE; HLA-B; POLYMORPHISMS; PROGRESSION; PROTEINS; KIR3DL1; AIDS AB A new study reports that specific combinations of killer immunoglobulin-like receptor and HLA-B alleles influence AIDS progression and plasma HIV RNA levels in HIV-infected individuals. These results suggest that natural killer cells have an important role in recognizing and limiting HIV infection. C1 Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Univ Oxford, AIDS Res Ctr, Oxford OX1 3SY, England. Univ Oxford, Dept Paediat, Oxford OX1 3SY, England. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM Philip.Goulder@paediatrics.ox.ac.uk NR 15 TC 24 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 2007 VL 39 IS 6 BP 708 EP 710 DI 10.1038/ng0607-708 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 173FO UT WOS:000246859100011 PM 17534364 ER PT J AU Martin, MP Qi, Y Gao, XJ Yamada, E Martin, JN Pereyra, F Colombo, S Brown, EE Shupert, WL Phair, J Goedert, JJ Buchbinder, S Kirk, GD Telenti, A Connors, M O'Brien, SJ Walker, BD Parham, P Deeks, SG McVicar, DW Carrington, M AF Martin, Maureen P. Qi, Ying Gao, Xiaojiang Yamada, Eriko Martin, Jeffrey N. Pereyra, Florencia Colombo, Sara Brown, Elizabeth E. Shupert, W. Lesley Phair, John Goedert, James J. Buchbinder, Susan Kirk, Gregory D. Telenti, Amalio Connors, Mark O'Brien, Stephen J. Walker, Bruce D. Parham, Peter Deeks, Steven G. McVicar, Daniel W. Carrington, Mary TI Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1 SO NATURE GENETICS LA English DT Article ID NATURAL-KILLER-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; IMMUNOGLOBULIN-LIKE RECEPTOR; IMMUNODEFICIENCY-VIRUS TYPE-1; CLASS-I MOLECULES; MHC CLASS-I; INHIBITORY RECEPTORS; SELF-TOLERANCE; AIDS; INFECTION AB Allotypes of the natural killer ( NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)(+) individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection. C1 Sci Applicat Int Corp Frederick Inc, NCI, Lab Genom Divers, Frederick, MD 21702 USA. Sci Applicat Int Corp Frederick Inc, NCI, Lab Expt Immunol, Frederick, MD 21702 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94105 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Div, Boston, MA 02129 USA. Univ Lausanne, Inst Microbiol, CH-1011 Lausanne, Switzerland. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NIAID, Rocky Mt Lab, Hamilton, MT 59840 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. HIV Res Sect, San Francisco Dept Publ Hlth, San Francisco, CA 94102 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. RP Carrington, M (reprint author), Sci Applicat Int Corp Frederick Inc, NCI, Lab Genom Divers, POB B,Bldg 560, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov RI Kirk, Gregory/A-8484-2009; SHCS, all/G-4072-2011; SHCS, int. coll. A/G-4083-2011; McVicar, Daniel/G-1970-2015 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [P30 AI027763]; NIDA NIH HHS [R01 DA004334, R01-DA04334, R56 DA004334] NR 45 TC 407 Z9 416 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 2007 VL 39 IS 6 BP 733 EP 740 DI 10.1038/ng2035 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 173FO UT WOS:000246859100017 PM 17496894 ER PT J AU Muller, MR Rao, A AF Mueller, Martin R. Rao, Anjana TI Linking calcineurin activity to leukemogenesis SO NATURE MEDICINE LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA; T-CELL LEUKEMIA; NFAT; ACTIVATION; LYMPHOMAS; PATHWAY; NOTCH1; ROLES AB Aberrant activation of the protein phosphatase calcineurin is found in various cancer types. Inhibition of calcineurin leads to a rapid clearance of leukemic cells and significantly improves animal survival in two mouse models of acute T lymphoblastic leukemia. C1 Harvard Univ, Med Sch, Dept Pathol, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. RP Muller, MR (reprint author), Harvard Univ, Med Sch, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu NR 14 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 2007 VL 13 IS 6 BP 669 EP 671 DI 10.1038/nm0607-669 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 176KQ UT WOS:000247084300015 PM 17554330 ER PT J AU Williams, MA Dang, S Kanwisher, NG AF Williams, Mark A. Dang, Sabin Kanwisher, Nancy G. TI Only some spatial patterns of fMRI response are read out in task performance SO NATURE NEUROSCIENCE LA English DT Article ID VISUAL-CORTEX; MICROSTIMULATION; REPRESENTATIONS; RECOGNITION AB Classification methods show that the spatial pattern of a functional magnetic resonance imaging response across the cortex contains category information, but whether such patterns are used, or 'read out', in behavioral performance remains untested. We show that although the spatial pattern in both the retinotopic and lateral occipital cortex (LOC) in humans contains category information, only in the LOC is the pattern stronger for correct than for incorrect trials. Thus, some, but not all, spatial patterns are read out during task performance. C1 MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. Macquarie Univ, Macquarie Ctr Cognit Sci, Sydney, NSW 2109, Australia. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Williams, MA (reprint author), MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM markaw@mit.edu OI Williams, Mark/0000-0002-3897-5167 FU NEI NIH HHS [R01 EY013455-05A1, R01 EY013455]; PHS HHS [13455] NR 14 TC 94 Z9 94 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUN PY 2007 VL 10 IS 6 BP 685 EP 686 DI 10.1038/nn1900 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 172JI UT WOS:000246799800009 PM 17486103 ER PT J AU Yoshii, A Constantine-Paton, M AF Yoshii, Akira Constantine-Paton, Martha TI BDNF induces transport of PSD-95 to dendrites through PI3K-AKT signaling after NMDA receptor activation SO NATURE NEUROSCIENCE LA English DT Article ID LONG-TERM POTENTIATION; SYNAPTIC PLASTICITY; ENDOPLASMIC-RETICULUM; HIPPOCAMPAL-NEURONS; CALCIUM CHANNELS; LIPID RAFTS; SYNAPSES; PROTEINS; NEUROTROPHINS; TRANSMISSION AB The N-methyl-D-aspartate receptor (NMDAR), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95) and phosphatidylinositol 3-kinase (PI3K) have all been implicated in long-term potentiation. Here we show that these molecules are involved in a single pathway for synaptic potentiation. In visual cortical neurons in young rodents, the neurotrophin receptor TrkB is associated with PSD-95. When BDNF is applied to cultured visual cortical neurons, PSD-95-labeled synaptic puncta enlarge, and fluorescent recovery after photobleaching (FRAP) reveals increased delivery of green fluorescent protein-tagged PSD-95 to the dendrites. The recovery of fluorescence requires TrkB, signaling through PI3K and the serine-threonine kinase Akt, and an intact Golgi apparatus. Stimulation of NMDARs mimics the PSD-95 trafficking that is induced by BDNF but requires active BDNF and PI3K. Furthermore, local dendritic contact with a BDNF-coated microsphere induces PSD-95 FRAP throughout the dendrites of the stimulated neuron, suggesting that this mechanism induces rapid neuron-wide synaptic increases in PSD-95 and refinement whenever a few robust inputs activate the NMDAR-BDNF-PI3K pathway. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Yoshii, A (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ayoshii@mit.edu FU NEI NIH HHS [R01EY014074, R01EY006039] NR 50 TC 130 Z9 131 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUN PY 2007 VL 10 IS 6 BP 702 EP 711 DI 10.1038/nn1903 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 172JI UT WOS:000246799800012 PM 17515902 ER PT J AU de Fougerolles, A Vornlocher, HP Maraganore, J Lieberman, J AF de Fougerolles, Antonin Vornlocher, Hans-Peter Maraganore, John Lieberman, Judy TI Interfering with disease: a progress report on siRNA-based therapeutics SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; RETRACTED ARTICLE. SEE; INHIBITS TUMOR-GROWTH; RNAI ENZYME COMPLEX; DOUBLE-STRANDED-RNA; ADULT-MOUSE BRAIN; ACUTE LUNG INJURY; IN-VIVO; MAMMALIAN-CELLS; GENE DELIVERY AB RNA interference (RNAi) quietly crept into biological research in the 1990s when unexpected gene-silencing phenomena in plants and flatworms first perplexed scientists. Following the demonstration of RNAi in mammalian cells in 2001, it was quickly realized that this highly specific mechanism of sequence-specific gene silencing might be harnessed to develop a new class of drugs that interfere with disease-causing or disease-promoting genes. Here we discuss the considerations that go into developing RNAi-based therapeutics starting from in vitro lead design and identification, to in vivo pre-clinical drug delivery and testing. We conclude by reviewing the latest clinical experience with RNAi therapeutics. C1 Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA. Alnylam Europe AG, D-95326 Kulmbach, Germany. CBR Inst Biomed Res, Boston, MA 02115 USA. RP de Fougerolles, A (reprint author), Alnylam Pharmaceut Inc, 300 3rd St, Cambridge, MA 02142 USA. EM tdefougerolles@alnylam.com; Lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI056900, AI070302] NR 104 TC 728 Z9 746 U1 29 U2 209 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD JUN PY 2007 VL 6 IS 6 BP 443 EP 453 DI 10.1038/nrd2310 PG 11 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 175DE UT WOS:000246992000013 PM 17541417 ER PT J AU Molyneaux, BJ Arlotta, P Menezes, JRL Macklis, JD AF Molyneaux, Bradley J. Arlotta, Paola Menezes, Joao R. L. Macklis, Jeffrey D. TI Neuronal subtype specification in the cerebral cortex SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID CORTICOSPINAL MOTOR-NEURONS; CENTRAL-NERVOUS-SYSTEM; SUBCORTICAL PROJECTION NEURONS; CAJAL-RETZIUS CELLS; RADIAL GLIAL-CELLS; GENE-EXPRESSION; MAMMALIAN TELENCEPHALON; PROGENITOR CELLS; CORTICAL INTERNEURONS; TRANSCRIPTION FACTOR AB In recent years, tremendous progress has been made in understanding the mechanisms underlying the specification of projection neurons within the mammalian neocortex. New experimental approaches have made it possible to identify progenitors and study the lineage relationships of different neocortical projection neurons. An expanding set of genes with layer and neuronal subtype specificity have been identified within the neocortex, and their function during projection neuron development is starting to be elucidated. Here, we assess recent data regarding the nature of neocortical progenitors, review the roles of individual genes in projection neuron specification and discuss the implications for progenitor plasticity. C1 Harvard Univ, Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg,Program Neurosci,Med Sch, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair, Dept Neurol,Program Neurosci,Med Sch, Boston, MA 02115 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02114 USA. Univ Fed Rio de Janeiro, Lab Neuroanat Celular, Dept Anat, Inst Ciencias Biomed,Programa Ciencias Morfol, Rio De Janeiro, Brazil. RP Macklis, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg,Program Neurosci,Med Sch, Boston, MA 02115 USA. EM jeffrey_macklis@hms.harvard.edu RI Menezes, Joao/D-5668-2012; PCM, PG/D-1034-2013; OI Molyneaux, Bradley/0000-0002-3377-1229 FU NINDS NIH HHS [NS49553, NS41590, NS45523] NR 134 TC 627 Z9 634 U1 12 U2 73 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JUN PY 2007 VL 8 IS 6 BP 427 EP 437 DI 10.1038/nrn2151 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 170JF UT WOS:000246658800012 PM 17514196 ER PT J AU Omer, HA Hussein, MR AF Omer, Hyder A. Hussein, Mahmoud R. TI Primary renal lymphoma SO NEPHROLOGY LA English DT Article ID KIDNEY C1 King Khalid Univ, Coll Med, Dept Med, Nephrol Sect,Assir Cent Hosp, Abha, Saudi Arabia. Assuit Univ Hosp, Dept Pathol, Assiut, Egypt. Univ Wisconsin, Sch Med, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Omer, HA (reprint author), King Khalid Univ, Coll Med, Dept Med, Nephrol Sect,Assir Cent Hosp, Abha, Saudi Arabia. NR 3 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2007 VL 12 IS 3 BP 314 EP 315 DI 10.1111/j.1440-1797.2007.00783.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 173QX UT WOS:000246888700017 PM 17498130 ER PT J AU Zhao, Z Xiang, ZM Haroutunian, V Buxbaum, JD Stetka, B Pasinetti, GM AF Zhao, Zhong Xiang, Zhongmin Haroutunian, Vahram Buxbaum, Joseph D. Stetka, Breton Pasinetti, Giulio Maria TI Insulin degrading enzyme activity selectively decreases in the hippocampal formation of cases at high risk to develop Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE IDE; MCI; CDR; beta-amyloid ID MILD COGNITIVE IMPAIRMENT; AMYLOID BETA-PROTEIN; EXTRACELLULAR LEVELS; A-BETA; DEGRADATION; BRAIN; MECHANISMS; OLIGOMERS; PEPTIDE AB In this study we report that the mem brane-bound, but not cytosolic insulin degrading enzyme (IDE) protein concentration and IDE activity are significantly decreased in the hippocampal formation of cases affected by mild cognitive impairment (MCI) which are at high risk to develop Alzheimer's disease (AD), relative to normal neurological controls. Membrane-bound IDE protein concentrations and activity in the hippocampal formation continued to decrease during the conversion from MCI to mild-severe AD. This selective decrease in hippocampal membrane-bound, but not cytosolic, IDE concentration and activity was tissue specific since no changes in either membrane-bound or cytosolic IDE were found in the occipital cortex of the same cases examined. Most interestingly, the decreased hippocampal membrane-bound IDE protein activity negatively correlated with brain beta-amyloid (A beta)X-42 content in MCI and in AD brain. The study tentatively suggests that interventions aimed at promoting membrane-bound IDE activities in the brain of MCI cases may help to prevent the onset and possibly the progression into AD through mechanisms involving the clearance of monomeric A beta from the brain. (c) 2006 Elsevier Inc. All rights reserved. C1 Mt Sinai Sch Med, Neuroinflammat Res Labs, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, GRECC, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Neuroinflammat Res Labs, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu OI Buxbaum, Joseph/0000-0001-8898-8313 FU NIA NIH HHS [AG13799, AG14239, AG14766] NR 18 TC 68 Z9 73 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUN PY 2007 VL 28 IS 6 BP 824 EP 830 DI 10.1016/j.neurobiolaging.2006.05.001 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 164SB UT WOS:000246253300003 PM 16769157 ER PT J AU Cantuti-Castelvetri, I Keller-McGandy, C Bouzou, B Asteris, G Clark, TW Frosch, MP Standaert, DG AF Cantuti-Castelvetri, Ippolita Keller-McGandy, Christine Bouzou, Berengere Asteris, Georgios Clark, Timothy W. Frosch, Matthew P. Standaert, David G. TI Effects of gender on nigral gene expression and parkinson disease SO NEUROBIOLOGY OF DISEASE LA English DT Article ID NIGROSTRIATAL DOPAMINERGIC SYSTEM; MPTP-INDUCED NEUROTOXICITY; POSTMORTEM HUMAN BRAIN; SUBSTANTIA-NIGRA; SEX-DIFFERENCES; MESSENGER-RNA; UBIQUITIN-PROTEASOME; ALPHA-SYNUCLEIN; MICROARRAY DATA; PARS COMPACTA AB To identify gene expression patterns in human dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of male and female control and Parkinson disease (PD) patients, we harvested DA neurons from frozen SNc from 16 subjects (4 male PDs, 4 female PDs, 4 male and 4 female controls) using Laser Capture microdissection and microarrays. We assessed for enrichment of functional categories with a hypergeometric distribution. The data were validated with QPCR. We observed that gender has a pervasive effect on gene expression in DA neurons. Genes upregulated in females relative to males are mainly involved in signal transduction and neuronal maturation, while in males some of the upregulated genes (alpha-synuclein and PINK]) were previously implicated in the pathogenesis of PD. In females with PD we found alterations in genes with protein kinase activity, genes involved in proteolysis and WNT signaling pathway, while in males with PD there were alterations in protein-binding proteins and copper-binding proteins. Our data reveal broad gender-based differences in gene expression in human dopaminergic neurons of SNc that may underlie the predisposition of males to PD. Moreover, we show that gender influences the response to PD, suggesting that the nature of the disease and the response to treatment may be gender-dependent. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Neurol Dept, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Massgen Inst Neurodegenerat Dis, Ctr Interdisciplinary Informat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Cantuti-Castelvetri, I (reprint author), Massachusetts Gen Hosp, Neurol Dept, 114 16th St CNY114-2250, Charlestown, MA 02129 USA. EM can-cas@helix.mgh.harvard.edu OI Clark, Timothy/0000-0003-4060-7360; Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG005134, P50 AG005134]; NIMH NIH HHS [R24 MH068855, R24-MH068855]; NINDS NIH HHS [P50 NS038372-08, NS38372, P50 NS038372, P50 NS038372-06A1, P50 NS038372-06A1S1, P50 NS038372-07] NR 69 TC 95 Z9 98 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN PY 2007 VL 26 IS 3 BP 606 EP 614 DI 10.1016/j.nbd.2007.02.009 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 177II UT WOS:000247146400011 PM 17412603 ER PT J AU Wong, HK Muftuoglu, M Beck, G Imam, SZ Bohr, VA Wilson, DM AF Wong, Heng-Kuan Muftuoglu, Meltem Beck, Gad Imam, Syed Z. Bohr, Vilhelm A. Wilson, David M., III TI Cockayne syndrome B protein stimulates apurinic endonuclease 1 activity and protects against agents that introduce base excision repair intermediates SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION-COUPLED REPAIR; HUMAN APURINIC ENDONUCLEASE; ABASIC SITE RECOGNITION; STRAND BREAK REPAIR; CSB GENE-PRODUCT; DNA-REPAIR; XERODERMA-PIGMENTOSUM; POLY(ADP-RIBOSE) POLYMERASE; MAJOR HUMAN AB The Cockayne syndrome B (CSB) protein-defective in a majority of patients suffering from the rare autosomal disorder CS-is a member of the SWI2/SNF2 family with roles in DNA repair and transcription. We demonstrate herein that purified recombinant CSB and the major human apurinic/apyrimidinic (AP) endonuclease, APE1, physically and functionally interact. CSB stimulates the AP site incision activity of APE1 on normal (i.e. fully paired) and bubble AP-DNA substrates, with the latter being more pronounced ( =up to 6-fold). This activation is ATP-independent, and specific for the human CSB and full-length APE1 protein, as no CSB-dependent stimulation was observed with Escherichia coli endonuclease IV or an N-terminal truncated APE1 fragment. CSB and APE1 were also found in a common protein complex in human cell extracts, and recombinant CSB, when added back to CSB-deficient whole cell extracts, resulted in increased total AP site incision capacity. Moreover, human fibroblasts defective in CSB were found to be hypersensitive to both methyl methanesulfonate (MMS) and 5-hydroxymethyl 20-deoxyuridine, agents that introduce base excision repair (BER) DNA substrates/intermediates. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wilsonda@grc.nia.nih.gov FU Intramural NIH HHS NR 81 TC 63 Z9 66 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN PY 2007 VL 35 IS 12 BP 4103 EP 4113 DI 10.1093/nar/gkm404 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186ZS UT WOS:000247817700022 PM 17567611 ER PT J AU Li, J Berbeco, R Distel, RJ Janne, PA Wang, LL Makrigiorgos, GM AF Li, Jin Berbeco, Ross Distel, Robert J. Janne, Pasi A. Wang, Lilin Makrigiorgos, G. Mike TI s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA-melting: new potential for multiplex genetic analysis SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CELL LUNG-CANCER; SINGLE-NUCLEOTIDE POLYMORPHISMS; POINT MUTATIONS; HIGH-THROUGHPUT; CAPILLARY-ELECTROPHORESIS; PROGNOSTIC-FACTORS; SOMATIC MUTATIONS; MISMATCH CLEAVAGE; P53 MUTATIONS; GEFITINIB AB The rapidly growing understanding of human genetic pathways, including those that mediate cancer biology and drug response, leads to an increasing need for extensive and reliable mutation screening on a population or on a single patient basis. Here we describe s-RT-MELT, a novel technology that enables highly expanded enzymatic mutation scanning in human samples for germline or low-level somatic mutations, or for SNP discovery. GC-clamp-containing PCR products from interrogated and wild-type samples are hybridized to generate mismatches at the positions of mutations over one or multiple sequences in-parallel. Mismatches are converted to double-strand breaks using a DNA endonuclease (Surveyor (TM)) and oligonucleotide tails are enzymatically attached at the position of mutations. A novel application of PCR enables selective amplification of mutation-containing DNA fragments. Subsequently, melting curve analysis, on conventional or nano-technology real-time PCR platforms, detects the samples that contain mutations in a high-throughput and closed-tube manner. We apply s-RT-MELT in the screening of p53 and EGFR mutations in cell lines and clinical samples and demonstrate its advantages for rapid, multiplexed mutation scanning in cancer and for genetic variation screening in biology and medicine. C1 Harvard Univ, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Dana Farber Brigham & Womens Canc Ctr,Sch Med, Boston, MA 02115 USA. Harvard Univ, Translat Res Lab, Ctr Clin & Translat Res, Dana Farber Brigham & Womens Canc Ctr,Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Lowe Ctr Thorac Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Dept Radiat Oncol, Div Genom Stabil & DNA Repair, Dana Farber Brigham & Womens Canc Ctr,Sch Med, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NCI NIH HHS [1 R21 CA111994-01, CA 115439-01, T32 CA009078, R21 CA115439, R21 CA111994, 5 T32 CA09078] NR 46 TC 18 Z9 21 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN PY 2007 VL 35 IS 12 AR e84 DI 10.1093/nar/gkm403 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186ZS UT WOS:000247817700033 PM 17545195 ER PT J AU Meng, X Thibodeau-Beganny, S Jiang, T Joung, JK Wolfe, SA AF Meng, Xiangdong Thibodeau-Beganny, Stacey Jiang, Tao Joung, J. Keith Wolfe, Scot A. TI Profiling the DNA-binding specificities of engineered Cys2His2 zinc finger domains using a rapid cell-based method SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ARTIFICIAL TRANSCRIPTION FACTORS; IMMUNODEFICIENCY-VIRUS TYPE-1; CONTROLLING GENE-EXPRESSION; RECOGNITION CODE; PROTEIN-DNA; CHIMERIC NUCLEASES; SELECTION SYSTEM; BUILDING-BLOCKS; PHAGE DISPLAY; CONSTRUCTION AB The C2H2 zinc finger is the most commonly utilized framework for engineering DNA-binding domains with novel specificities. Many different selection strategies have been developed to identify individual fingers that possess a particular DNA-binding specificity from a randomized library. In these experiments, each finger is selected in the context of a constant finger framework that ensures the identification of clones with a desired specificity by properly positioning the randomized finger on the DNA template. Following a successful selection, multiple zinc-finger clones are typically recovered that share similarities in the sequences of their DNA-recognition helices. In principle, each of the clones isolated from a selection is a candidate for assembly into a larger multi-finger protein, but to date a high-throughput method for identifying the most specific candidates for incorporation into a final multi-finger protein has not been available. Here we describe the development of a specificity profiling system that facilitates rapid and inexpensive characterization of engineered zinc-finger modules. Moreover, we demonstrate that specificity data collected using this system can be employed to rationally design zinc fingers with improved DNA-binding specificities. C1 Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wolfe, SA (reprint author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, 364 Plantat St, Worcester, MA 01605 USA. EM scot.wolfe@umassmed.edu FU NIGMS NIH HHS [R01 GM068110, R01 GM072621, R01 GM069906, 1R01GM068110]; NIH HHS [DP1 OD006862] NR 43 TC 16 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN PY 2007 VL 35 IS 11 AR e81 DI 10.1093/nar/gkm385 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 186ZQ UT WOS:000247817500034 PM 17537811 ER PT J AU Lata, PF Elliott, ME AF Lata, Paul F. Elliott, Mary E. TI Patient assessment in the diagnosis, prevention, and treatment of osteoporosis SO NUTRITION IN CLINICAL PRACTICE LA English DT Review ID BONE-MINERAL DENSITY; FRACTURE INTERVENTION TRIAL; X-RAY ABSORPTIOMETRY; VITAMIN-D STATUS; SEROTONIN-REUPTAKE INHIBITORS; POPULATION-BASED COHORT; POSTMENOPAUSAL WOMEN; VERTEBRAL FRACTURE; HIP FRACTURE; BIOCHEMICAL MARKERS AB Assessment of the patient with osteoporosis includes history and physical examination, laboratory testing, and imaging studies. Information gathered during this assessment assists clinicians in targeting strategies to prevent fractures. The medical history should contain items such as personal and family history of fractures, lifestyle, intake of substances such as vitamin D, calcium, corticosteroids, and other medications. The physical examination can reveal relevant information such as height loss and risk of falls. Bone mineral density (BMD), most commonly determined by dual-energy x-ray absorptiometry, best predicts fracture risk in patients without previous fracture. BMD testing is most efficient in women over 65 years old but is also helpful for men and women with risk factors. Serial BMD tests can identify individuals losing bone mass, but clinicians should be aware of what constitutes a significant change. Laboratory testing can detect other risk factors and can provide clues to etiology. Selection of laboratory tests should be individualized, as there is no consensus regarding which tests are optimal. Biochemical markers of bone turnover have a potential role in fracture risk assessment and in gauging response to therapy, but are not widely used at present. Clinicians should be aware of problems with vitamin D measurement, including seasonal variation, variability among laboratories, and the desirable therapeutic range. Careful assessment of the osteoporotic patient is essential in developing a comprehensive plan that reduces fracture risk and improves quality of life. C1 Bay Area Med Ctr, Case Management Serv, Marinette, WI 54143 USA. Univ Wisconsin, Sch Pharm, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Lata, PF (reprint author), Bay Area Med Ctr, Case Management Serv, 3100 Shore Dr, Marinette, WI 54143 USA. EM plata@bamc.org NR 133 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0884-5336 J9 NUTR CLIN PRACT JI Nutr. Clin. Pract. PD JUN PY 2007 VL 22 IS 3 BP 261 EP 275 DI 10.1177/0115426507022003261 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 217CT UT WOS:000249926700003 PM 17507727 ER PT J AU Bennett, GG Wolin, KY Askew, S Fletcher, R Emmons, KM AF Bennett, Gary G. Wolin, Kathleen Y. Askew, Sandy Fletcher, Robert Emmons, Karen M. TI Immigration and obesity among lower income blacks SO OBESITY LA English DT Article DE nativity; acculturation; immigrant; blacks ID MULTIETHNIC POPULATIONS; SOCIOECONOMIC-STATUS; HISPANIC IMMIGRANTS; HEALTHY DIRECTIONS; MEXICAN-AMERICANS; CANCER PREVENTION; WORKING-CLASS; ACCULTURATION; US; OVERWEIGHT AB Objective: Our objective was to examine the associations of nativity, immigrant generation, and language acculturation with obesity among lower income black adult men and women. Research Methods and Procedures: Data from 551. black adult men and women were collected from participants in the Healthy Directions-Health Centers Study. Race/ethnicity and nativity were self-reported. Language acculturation was defined using participants' first language, preferred reading language, and language spoken at home. Mixed model logistic regression models were estimated to account for within-health center clustering. Results: Foreign-born blacks had a lower obesity risk, compared with all U.S.-born participants, in multivariable analyses [odds ratio (OR) = 0.57, 95% confidence interval (CI), 0.38, 0.84]. Among U.S.-born participants, those with foreign-born parents were significantly less likely to be obese than individuals with U.S.-born parents (OR = 0.54; 95% CI, 0.37, 0.80). Low-moderate language acculturation also decreased the odds of being obese (OR = 0.45; 95% CI, 0.23, 0.88). Discussion: Our findings suggest a protective effect of foreign-born status and low-moderate language acculturation on obesity risk among lower income black immigrants. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Bennett, GG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 44 Binney St,SM256, Boston, MA 02115 USA. EM gbennett@hsph.harvard.edu RI Wolin, Kathleen/I-2154-2014 OI Wolin, Kathleen/0000-0001-7950-9042 FU NCI NIH HHS [R01 CA098864, 1R25 CA100600-01A1, 5P01 CA75308, P01 CA075308] NR 21 TC 19 Z9 19 U1 3 U2 5 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1930-7381 J9 OBESITY JI Obesity PD JUN PY 2007 VL 15 IS 6 BP 1391 EP 1394 DI 10.1038/oby.2007.166 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 180ZG UT WOS:000247405900007 PM 17557975 ER PT J AU Gragnoli, C AF Gragnoli, Claudia TI Kir6.2 (KCNJ11) E23K variant in Type 2 diabetes in Italians SO OBESITY AND METABOLISM-MILAN LA English DT Article DE association; Italian; Kir6.2 (KCNJ11) E23K; type 2 diabetes ID GENE C1 [Gragnoli, Claudia] Bios Multi Diagnost Biotech & Res Fdn, I-00197 Rome, Italy. [Gragnoli, Claudia] Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. [Gragnoli, Claudia] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gragnoli, Claudia] Univ Roma Tor Vergata, Rome, Italy. RP Gragnoli, C (reprint author), Bios Multi Diagnost Biotech & Res Fdn, Via Chelini 20, I-00197 Rome, Italy. EM Claudia.Gragnoli@gmail.com FU Rotary Foundation International; NIH Training Program in Endocrinology and Diabetes [DK07028]; Massachusetts General Hospital, Boston, MA [DK30834] FX We thank the entire network of medical and nursing staff of private, public and academic clinical centers from center of Italy for their contribution to recruitment of T2D patients, families and control subjects. A special thank goes to the medical nursing, molecular biology and administrative staff of ical, Bios MuIti-Diagnostic Biotech and Research Foundation in Rome for their precious help with the recruitment, blood withdrawal, DNA extraction and generous financial support. CG expresses deep gratitude to the Rotary Foundation International for supporting genetic studies of T2D in Italians. CG has received support by NIH Training Program in Endocrinology and Diabetes DK07028 grant for the genetic studies of T21D in Italians. This study was supported in part by NIH grant DK30834 of Dr. Joel Habener at Massachusetts General Hospital, Boston, MA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1825-3865 J9 OBES METAB-MILAN JI Obes. Metab.-Milan PD JUN PY 2007 VL 3 IS 2 BP 97 EP 98 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 339HI UT WOS:000258568300006 ER PT J AU O'Neill, MS Veves, A Sarnat, JA Zanobetti, A Gold, DR Economides, PA Horton, ES Schwartz, J AF O'Neill, M. S. Veves, A. Sarnat, J. A. Zanobetti, A. Gold, D. R. Economides, P. A. Horton, E. S. Schwartz, J. TI Air pollution and inflammation in type 2 diabetes: a mechanism for susceptibility SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; INTERCELLULAR-ADHESION MOLECULE-1; ENDOTHELIAL FUNCTION; ATRIAL-FIBRILLATION; RISK; PARTICLES; ASSOCIATION; EXPOSURE; MARKERS; BLOOD AB Background: Particulate air pollution has been associated with several adverse cardiovascular health outcomes, and people with diabetes may be especially vulnerable. One potential pathway is inflammation and endothelial dysfunction - processes in which cell adhesion molecules and inflammatory markers play important roles. Aim: To examine whether plasma levels of soluble intercellular adhesion molecule 1 ( ICAM-1), vascular cell adhesion molecule 1 ( VCAM-1) and von Willebrand factor ( vWF) were associated with particle exposure in 92 Boston area residents with type 2 diabetes. Methods: Daily average ambient levels of air pollution ( fine particles ( PM2.5), black carbon ( BC) and sulphates) were measured approximately 500 m from the patient examination site and evaluated for associations with ICAM-1, VCAM-1 and vWF. Linear regressions were fit to plasma levels of ICAM-1, VCAM-1 and vWF, with the particulate pollutant index, apparent temperature, season, age, race, sex, glycosylated haemoglobin, cholesterol, smoking history and body mass index as predictors. Results: Air pollutant exposure measures showed consistently positive point estimates of association with the inflammatory markers. Among participants not taking statins and those with a history of smoking, associations between PM2.5, BC and VCAM-1 were particularly strong. Conclusions: These results corroborate evidence suggesting that inflammatory mechanisms may explain the increased risk of air pollution-associated cardiovascular events among those with diabetes. C1 Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Emory Univ, Sch Publ Hlth, Atlanta, GA 30322 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Ctr Endocrinol & Metab, Nicosia, Cyprus. Joslin Diabet Ctr, Boston, MA 02215 USA. RP O'Neill, MS (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 6631 SPH Tower,109 S Observ, Ann Arbor, MI 48109 USA. EM marieo@umich.edu RI feng, yongzhong/F-5090-2012 OI feng, yongzhong/0000-0002-5202-4368 FU NCRR NIH HHS [M01 RR001032, RR 01032]; NIDDK NIH HHS [2P30-DK-36836]; NIEHS NIH HHS [2 T32 ES07069-24, ES00002, P01 ES009825, P30 ES000002, T32 ES007069] NR 39 TC 126 Z9 129 U1 2 U2 20 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JUN PY 2007 VL 64 IS 6 BP 373 EP 379 DI 10.1136/oem.2006.030023 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 169LS UT WOS:000246594300004 PM 17182639 ER PT J AU Zhang, HX Hang, JQ Wang, XR Zhou, W Sun, BX Dai, HL Su, L Christiani, DC AF Zhang, Hongxi Hang, Jingqing Wang, Xiaorong Zhou, Wei Sun, Bixiong Dai, Helian Su, Li Christiani, David C. TI TNF polymorphisms modify endotoxin exposure-associated longitudinal lung function decline SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA GENE; OBSTRUCTIVE PULMONARY-DISEASE; PROMOTER POLYMORPHISM; AIRWAY DISEASE; COAL-MINERS; COTTON DUST; COPD; INHALATION; SUSCEPTIBILITY AB Objectives: Endotoxin exposure induces airway inflammation, hyper-responsiveness and higher expression of tumour necrosis factor ( TNF). This study was conducted to investigate whether TNF polymorphisms modify the effect of endotoxin exposure on chronic declines in lung function. Methods: Associations between TNF and LTA polymorphisms, endotoxin exposure and lung function were analysed in 263 cotton workers and 230 silk workers as a reference group, who were prospectively followed for 20 years. Multiple linear regression models were used to assess the association, with adjustment for smoking and other covariates. Results: Endotoxin exposure was associated with faster lung function decline among genotypes associated with higher TNF expression levels, with estimates of annual FEV1 change in relation to endotoxin exposure of -2.9 ml and -6.8 ml in the G/G and G/A+AA genotypes, respectively, for the TNF polymorphism; and 2.0 ml, -4.0 ml and -3.6 ml in A/A, A/G and G/G genotypes, respectively, for the LTA polymorphism. When joint effects of endotoxin exposure and smoking were considered, the effect modification of TNF and LTA polymorphisms was prominent in never smokers. Conclusions: TNF and LTA polymorphisms may modify the association between occupational endotoxin exposure and longitudinal lung function decline, which was more clearly observed in never smokers. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu RI Lin, Sihao/A-8412-2012 FU FIC NIH HHS [D43 TW000828, TW00828]; NIOSH CDC HHS [R01 OH002421, R01OH02421] NR 30 TC 7 Z9 8 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JUN PY 2007 VL 64 IS 6 BP 409 EP 413 DI 10.1136/oem.2006.029025 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 169LS UT WOS:000246594300009 PM 17332138 ER PT J AU Ghobrial, J Ghobrial, IM Mitstades, C Leleu, X Hatjiharissi, E Moreau, AS Roccaro, A Schlossman, R Hideshima, T Anderson, KC Richardson, P AF Ghobrial, Joanne Ghobrial, Irene M. Mitstades, Constantine Leleu, Xavier Hatjiharissi, Evdoxia Moreau, Anne-Sophie Roccaro, Aldo Schlossman, Robert Hideshima, Teru Anderson, Kenneth C. Richardson, Paul TI Novel therapeutic avenues in myeloma: Changing the treatment paradigm SO ONCOLOGY-NEW YORK LA English DT Article ID REFRACTORY MULTIPLE-MYELOMA; LENALIDOMIDE PLUS DEXAMETHASONE; STEM-CELL TRANSPLANTATION; HIGH-DOSE DEXAMETHASONE; NEWLY-DIAGNOSED MYELOMA; SGN-40 ANTI-HUCD40 MAB; I CLINICAL-TRIAL; PHASE-I; ANTITUMOR-ACTIVITY; HSP90 INHIBITOR AB Our better understanding of the complex interaction of multiple myeloma (MM) cells with their bone marrow microenvironment and the signaling pathways that are dysregulated in this process has resulted in a dramatic increase in the therapeutic agents available for this disease. A number of these new agents have demonstrated significant activity in patients with MM. Over the past 5 years, three drugs have received approval from the US Food and Drug Administration for therapy in MM-bortezomib, thalidomide, and lenalidomide. To date, the choice of therapy for MM is not individualized according to the biologic characteristics of the disease, but future studies should enable us to identify patients who may benefit most from certain therapeutic interventions, and thus develop individualized therapy for MM. In this review, we will present some of the treatment algorithms currently developed for patients with MM and focus on established advances in therapy, specifically with thalidomide, bortezomib, and lenalidomide. We will also discuss some of the emerging novel therapeutic agents showing promise in phase I/II clinical trials in MM. C1 [Ghobrial, Joanne; Ghobrial, Irene M.; Mitstades, Constantine; Leleu, Xavier; Hatjiharissi, Evdoxia; Moreau, Anne-Sophie; Roccaro, Aldo; Schlossman, Robert; Hideshima, Teru; Anderson, Kenneth C.; Richardson, Paul] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Jerome Lipper Multiple Myel, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Jerome Lipper Multiple Myel, 44 Binney St, Boston, MA 02115 USA. EM irene_hobrial@dfci.harvard.edu NR 64 TC 14 Z9 14 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 2007 VL 21 IS 7 BP 785 EP 792 PG 8 WC Oncology SC Oncology GA 270RL UT WOS:000253737800001 PM 17722741 ER PT J AU Desjardins, AE Vakoc, BJ Bilenca, A Tearney, GJ Bouma, BE AF Desjardins, A. E. Vakoc, B. J. Bilenca, A. Tearney, G. J. Bouma, B. E. TI Estimation of the scattering coefficients of turbid media using angle-resolved optical frequency-domain imaging SO OPTICS LETTERS LA English DT Article ID COHERENCE TOMOGRAPHY AB Noninvasive measurements of the scattering coefficients of optically turbid media using angle-resolved optical frequency-domain imaging (OFDI) are demonstrated. It is shown that, by incoherently averaging OFDI reflectance signals acquired at different backscattering angles, speckle noise is reduced, allowing scattering coefficients to be extracted from a single A-line with much higher accuracy than with measurements from conventional OFDI and optical coherence tomography systems. Modeling speckle as a random phasor sum, the relationship between the measurement accuracy and the number of compounded angles is derived. The sensitivity analysis is validated with measurements from a tissue phantom. (C) 2007 Optical Society of America C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Desjardins, AE (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM adesjard@mit.edu FU NCI NIH HHS [R01 CA103769-04, R01 CA103769]; NHLBI NIH HHS [R01 HL076398, R01 HL076398-03] NR 14 TC 10 Z9 10 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JUN 1 PY 2007 VL 32 IS 11 BP 1560 EP 1562 DI 10.1364/OL.32.001560 PG 3 WC Optics SC Optics GA 186CL UT WOS:000247756600072 PM 17546188 ER PT J AU Kawai, T Paster, BJ Komatsuzawa, H Ernst, CWO Goncalves, RB Sasaki, H Ouhara, K Stashenko, PP Sugai, M Taubman, MA AF Kawai, T. Paster, B. J. Komatsuzawa, H. Ernst, C. W. O. Goncalves, R. B. Sasaki, H. Ouhara, K. Stashenko, P. P. Sugai, M. Taubman, M. A. TI Cross-reactive adaptive immune response to oral commensal bacteria results in an induction of receptor activator of nuclear factor-kappa B ligand (RANKL)-dependent periodontal bone resorption in a mouse model SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Actinobacillus actinomycetemcomitans; immunoglobulin G; 29-kDa outer membrane protein (Omp29); osteoprotegerin-Fc; Pasteurella pneumotropica; periodontal bone loss; RANKL; T cells ID OUTER-MEMBRANE PROTEIN; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PORPHYROMONAS-GINGIVALIS; OSTEOPROTEGERIN LIGAND; JUVENILE PERIODONTITIS; MUCOSAL IMMUNITY; DISEASE; LYMPHOCYTE; MICROFLORA; DIVERSITY AB Introduction: The present study examined whether induction of an adaptive immune response to orally colonizing non-pathogenic Pasteurella pneumotropica by immunization with the phylogenetically closely related bacterium, Actinobacillus actinomycetemcomitans, can result in periodontal bone loss in mice. Methods: BALB/c mice harboring P. pneumotropica (P. pneumotropica(+) mice) in the oral cavity or control P. pneumotropica-free mice were immunized with fixed A. actinomycetemcomitans. The animals were sacrificed on day 30, and the following measurements were carried out: (i) serum immunoglobulin G and gingival T-cell responses to A. actinomycetemcomitans and P. pneumotropica; (ii) periodontal bone loss; and (iii) identification of receptor activator of nuclear factor-kappa B ligand (RANKL) -positive T cells in gingival tissue. Results: Immunization with A. actinomycetemcomitans induced a significantly elevated serum immunoglobulin G response to the 29-kDa A. actinomycetemcomitans outer membrane protein (Omp29), which showed strong cross-reactivity with P. pneumotropica OmpA compared to results in the control non-immunized mice. The A. actinomycetemcomitans-immunized P. pneumotropica(+) mice developed remarkable periodontal bone loss in a RANKL-dependent manner, as determined by the abrogation of bone loss by treatment with osteoprotegerin-Fc. The T cells isolated from the gingival tissue of A. actinomycetemcomitans-immunized P. pneumotropica(+) mice showed an in vitro proliferative response to both A. actinomycetemcomitans and P. pneumotropica antigen presentation, as well as production of soluble(s)RANKL in the culture supernatant. Double-color confocal microscopy demonstrated that the frequency of RANKL(+) T cells in the gingival tissue of A. actinomycetemcomitans-immunized P. pneumotropica(+) mice was remarkably elevated compared to control mice. Conclusion: The induction of an adaptive immune response to orally colonizing non-pathogenic P. pneumotropica results in RANKL-dependent periodontal bone loss in mice. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Hiroshima Univ, Grad Sch Dent, Dept Microbiol, Hiroshima, Japan. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. EM tkawai@forsyth.org FU NIDCR NIH HHS [DE-09018, DE-14551, DE-03420] NR 34 TC 23 Z9 26 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD JUN PY 2007 VL 22 IS 3 BP 208 EP 215 DI 10.1111/j.1399-302X.2007.00348.x PG 8 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 163HU UT WOS:000246151500010 PM 17488448 ER PT J AU Friedlander, AH Cohen, SN AF Friedlander, Arthur H. Cohen, Stanley N. TI Panoramic radiographic atheromas portend adverse vascular events SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; INTIMA-MEDIA THICKNESS; CAROTID-ARTERY; RISK-FACTORS; ATHEROSCLEROSIS; CALCIFICATION; PLAQUES; STROKE; EXTENT; HEART AB Objective. This study sought to determine if calcified carotid artery atheromas (CCAA) imaged on panoramic radiographs portend an adverse vascular event. Study design. Medical records of 46 males (mean age 66) with a CCAA (Group 1) were reviewed for preimaging vascular risks and for cerebrovascular events subsequent to the radiograph. Matched controls (age, gender, ethnicity, and vascular risks) treated at the same hospital but never radiographed were identified (Group 2) and matched to their cohort. The medical records of Group 2 individuals were re-reviewed for development of vascular events occurring after the date of their cohort's radiograph. Results. Twenty adverse vascular events (myocardial infarct, stroke, revascularization procedure, transient ischemic attack, angina requiring hospitalization) occurred in twelve Group 1 patients and 6 events occurred in five Group 2 patients (P = 0.006). Conclusion. The incidental finding of a CCAA portends significant risk of a future, adverse vascular event. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA USA. EM arthur.friedlander@med.va.gov NR 28 TC 29 Z9 31 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JUN PY 2007 VL 103 IS 6 BP 830 EP 835 DI 10.1016/j.tripleo.2006.07.016 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 191AX UT WOS:000248103300018 PM 17261373 ER PT J AU Franco, RA AF Franco, Ramon A., Jr. TI Aminolevulinic acid 585 nm pulsed dye laser photodynamic treatment of laryngeal keratosis with atypia SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 110th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 17-20, 2006 CL Toronto, CANADA SP Amer Acad Otolaryngol Head & Neck Surg ID GLOTTAL DYSPLASIA; THERAPY; LESIONS; CANCER AB Objective: To evaluate the safety and efficacy of aminolevulinic acid photodynamic therapy (ALA-PDT) with the 585 nm pulsed dye laser. Methods: A 5-year prospective study was performed with 12 male patients with keratosis. Twenty percent ALA was sprayed into the larynx and activated with the 585 nm pulsed dye laser (PDL). Of the 12 patients, four were not included (one lost to follow-up, two developed cancer, one papillomatosis), which reduced the number to eight. Twenty-eight procedures were performed in these eight patients; 18 (64%) procedures were performed in the clinic setting. Results: There was a 78% reduction (range, 10% to 100%) in the keratosis. No major side effects were noted. Mean follow-up was 34.5 months (range, 12 to 50 months). There were no statistical differences between the outpatient and operating room treatments. Conclusions: ALA-PDL PDT is effective and safe in treating laryngeal keratosis in the awake clinic setting and reduces morbidity without sacrificing treatment efficacy. (C) 2007 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Div Laryngol, Boston, MA 02114 USA. RP Franco, RA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Div Laryngol, 243 Charles St, Boston, MA 02114 USA. EM ramon_franco@meei.harvard.edu NR 11 TC 4 Z9 4 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 2007 VL 136 IS 6 BP 882 EP 887 DI 10.1016/j.otohns.2007.01.026 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 176SE UT WOS:000247104400004 PM 17547974 ER PT J AU Avila, AD Thiagalingam, A Ruskin, JN Reddy, VY AF Avila, Andre D' Thiagalingam, Aravinda Ruskin, Jeremy N. Reddy, Vivek Y. TI Combined ventricular endocardial and epicardial substrate mapping using a sonomicrometry-based electroanatomical mapping system SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE catheter ablation; myocardial infarction; ventricular tachycardia; pericardium; epicardium ID HEALED MYOCARDIAL-INFARCTION; CATHETER ABLATION; PORCINE MODEL; NONISCHEMIC CARDIOMYOPATHY; RADIOFREQUENCY ABLATION; SINUS RHYTHM; TACHYCARDIA AB Background: Substrate mapping using a magnetic electroanatomical mapping system (MEAM) has been shown to accurately delineate the location/extent of scarred myocardium. This study examined the ability of a sonomicrometry-based electroanatomic mapping system (SEAM) to render endocardial and epicardial substrate maps of infarcted ventricular myocardium. Methods and Results: In 7 swine with healed myocardial infarctions, combined epicardial and endocardial left ventricular (LV) substrate maps were created with both SEAM and MEAM mapping systems using 246 +/- 68 and 244 +/- 44 points respectively. Scarred myocardium was identified based upon bipolar electrogram amplitude < 1.5 mV, and radiofrequency ablation lesions were delivered to the scar border as defined by the sonomicrometry mapping system. The LV endocardial chamber volume as defined by SEAM (125 +/- 46 ml) correlated well with that defined by the MEAM (137 45 ml, r=0.77, p < 0.05). The area of infarcted tissue as determined by SEAM was highly correlated with that determined by gross pathology (r=0.96 for endocardial scar and r=0.92 for epicardial scar p < 0.05). The scar area calculated by the SEAM system also correlated well with the scar area determined by the MEAM system (0.91 for endocardial scar and 0.90 for epicardial scar p < 0.05). Finally, the sonomicrometry-based system was able to guide the placement of radiofrequency ablation lesions to the borders of the scar. Conclusions: This study demonstrates that the sonomicrometry-based mapping can accurately reconstruct three-dimensional voltage maps of the endocardial and epicardial ventricular surfaces and guide the placement of ablation lesions along the scar border zone. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Avila, AD (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. EM adavila@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; FU NHLBI NIH HHS [K23 HL68064-02] NR 14 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JUN PY 2007 VL 30 IS 6 BP 781 EP 786 DI 10.1111/j.1540-8159.2007.00750.x PG 6 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 184YT UT WOS:000247679200010 PM 17547612 ER PT J AU Ballantyne, JC LaForge, KS AF Ballantyne, Jane C. LaForge, K. Steven TI Opioid dependence and addiction during opioid treatment of chronic pain SO PAIN LA English DT Review DE opioid analgesics; pain; substance-related disorders; opioid-related disorders ID LOW-BACK-PAIN; CHRONIC MUSCULOSKELETAL PAIN; GENOMEWIDE LINKAGE SCAN; PITUITARY-ADRENAL AXIS; CHRONIC NONCANCER PAIN; OFFICE-BASED TREATMENT; MORPHINE-TOLERANCE; SUBSTANCE-ABUSE; RECEPTOR GENE; DRUG-ABUSE C1 Massachusetts Gen Hosp, Div Pain Med, Pain Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Helsinki, Finnish Genome Ctr, FIN-00014 Helsinki, Finland. RP Ballantyne, JC (reprint author), Massachusetts Gen Hosp, Div Pain Med, Pain Ctr, 15 Parkman St,WACC 333, Boston, MA 02114 USA. EM jballantyne@partners.org FU NIDA NIH HHS [P60-DA05130] NR 216 TC 179 Z9 183 U1 8 U2 41 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD JUN PY 2007 VL 129 IS 3 BP 235 EP 255 DI 10.1016/j.pain.2007.03.028 PG 21 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 179JQ UT WOS:000247286200003 PM 17482363 ER PT J AU Levy, O Suter, EE Kalish, LA Russell, JD Scannon, PJ Guinan, EC AF Levy, Ofer Suter, Eugenie E. Kalish, Leslie A. Russell, Janice D. Scannon, Patrick J. Guinan, Eva C. TI Potential therapeutic intervention suggested by profound deficiency of neutrophil-derived bactericidal/permeability-increasing protein (BPI) and other alterations in LPS-directed innate immunity after myeloablative hematopoietic stem cell transplantation (HSCT) SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Dept Pediat, Boston, MA USA. XOMA US LLC, Berkeley, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN 1 PY 2007 VL 48 IS 6 BP 602 EP 602 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 161KN UT WOS:000246013900010 ER PT J AU Gutierrez, A Feng, H Langenau, D Prochownik, E Look, T AF Gutierrez, Alejandro Feng, Hui Langenau, David Prochownik, Edward Look, Thomas TI A conditional model of myc-induced T cell acute lymphoblastic leukemia in the zebrafish using Myc-estrogen receptor fusion transgenes SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN 1 PY 2007 VL 48 IS 6 BP 606 EP 606 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 161KN UT WOS:000246013900025 ER PT J AU Bernstein, H Isbey, S Ullrich, C Shaker, M AF Bernstein, Henry Isbey, Sarah Ullrich, Christina Shaker, Marcus TI An economic analysis of anemia prevention using reticulocyte hemoglobin content (CHr) SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Dartmouth Coll, Hannover, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN 1 PY 2007 VL 48 IS 6 BP 607 EP 608 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 161KN UT WOS:000246013900030 ER PT J AU Davies, JK Brennan, LL Nadler, LM Guinan, EC AF Davies, Jeff K. Brennan, Lisa L. Nadler, Lee M. Guinan, Eva C. TI Ex vivo alloantigen-specific costimulatory blockade in haploidentical bone marrow transplantation (BMT)-results of a pilot clinical study SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN 1 PY 2007 VL 48 IS 6 BP 621 EP 621 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 161KN UT WOS:000246013900086 ER PT J AU Kushak, RI Nestoridi, E Tsukurov, OI Ingelfinger, JR Grabowski, EF AF Kushak, Ralfail I. Nestoridi, Eirini Tsukurov, Olga I. Ingelfinger, Julie R. Grabowski, Eric F. TI Effect of shiga toxin on adhesion molecules expression on human giomerular endothelial cells SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN 1 PY 2007 VL 48 IS 6 BP 633 EP 633 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 161KN UT WOS:000246013900137 ER PT J AU DuBois, SG London, W Zhang, Y Cohn, SL Pearson, A Diller, L AF DuBois, Steven G. London, Wendy Zhang, Yang Cohn, Susan L. Pearson, Andrew Diller, Lisa TI Lung metastases in neuroblastoma at initial diagnosis: A report from the international neuroblastoma risk group project SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Florida, INRG Database & Childrens Oncol Grp Stat & Data C, Gainesville, FL USA. Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60611 USA. Univ Newcastle Upon Tyne, No Canc Res Inst, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN 1 PY 2007 VL 48 IS 6 BP 639 EP 639 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 161KN UT WOS:000246013900159 ER PT J AU Herbert, MR Kenet, T AF Herbert, Martha R. Kenet, Tal TI Brain abnormalities in language disorders and in autism SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID CORPUS-CALLOSUM SIZE; EVENT-RELATED POTENTIALS; CEREBRAL WHITE-MATTER; NON-SPEECH SOUNDS; DEVELOPMENTAL DYSLEXIA; HEAD CIRCUMFERENCE; SPECTRUM DISORDERS; ASSOCIATION CORTEX; MOTION PERCEPTION; EVOKED POTENTIALS AB It has been speculated that autism and specific language impairment share common underlying neural substrates because of the overlap in language impairment issues and evidence suggesting parallels in other domains and implying a possible shared genetic risk. Anatomically the two sets of disorders have generally been studied using different methodologies, but when identical methodologies have been used substantial similarities have been noted. Functionally there is a growing body of literature suggesting sensory perception abnormalities that have parallels in both conditions and that may be upstream of language abnormalities. Finding upstream mechanisms that impact language and non-language abnormalities in autism and specific language impairment would impact the orientation taken by translational attempts to use science to design treatments. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Ctr Child & Adolescent Dev, TRANSCEND Res Program, Medford, MA 02155 USA. RP Herbert, MR (reprint author), Massachusetts Gen Hosp, Dept Neurol, 149 13th St, Charlestown, MA 02129 USA. EM mherbert1@partners.org FU NINDS NIH HHS [NS48455] NR 132 TC 21 Z9 22 U1 6 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD JUN PY 2007 VL 54 IS 3 BP 563 EP + DI 10.1016/j.pcl.2007.02.007 PG 22 WC Pediatrics SC Pediatrics GA 187JD UT WOS:000247842800010 PM 17543910 ER PT J AU Mansbach, J Kunz, S Acholonu, U Clark, S Camargo, CA AF Mansbach, Jonathan Kunz, Sarah Acholonu, Uchechi Clark, Sunday Camargo, Carlos A., Jr. TI Evaluation of compliance with palivizumab recommendations in a multicenter study of young children presenting to the emergency department with bronchiolitis SO PEDIATRIC EMERGENCY CARE LA English DT Article DE palivizumab; bronchiolitis; RSV ID RESPIRATORY SYNCYTIAL VIRUS; CONGENITAL HEART-DISEASE; HIGH-RISK INFANTS; REDUCES HOSPITALIZATION; PREMATURE-INFANTS; NATIONAL-SURVEY; PROPHYLAXIS; INFECTION; DEXAMETHASONE; ADMISSION AB Objective: Monthly palivizumab injections from November to March decrease risk of respiratory syncytial virus (RSV)-related hospitalization during RSV season in high-risk infants born less than 35 weeks of gestation. Our objective was to investigate compliance with the American Academy of Pediatrics (AAP) recommendations for palivizumab prophylaxis among children who present to the emergency department (ED) with bronchiolitis. Methods: Seventeen centers, from 9 US states, performed a prospective, observational study of ED patients less than 2 years with an attending physician diagnosis of bronchiolitis. Researchers conducted a structured inter-view, followed by a chart review, and a 2-week follow-up phone call. Results: Of 825 eligible children, 624 (73%) were enrolled. According to AAP recommendations, 35 children (6%) should have received palivizumab, but only 17 (49%; 95% confidence interval, 31%-66%) did. Prophylaxis with palivizumab did not differ by US region (P > 0.50). The ED clinical presentations were similar when comparing those children that did and did not receive prophylaxis (all P > 0.27). Those receiving palivizumab were more likely to come to the ED using systemic corticosteroids (22% vs 7%; P 0.003) and to be treated with corticosteroids in the ED (31% vs 15%; P = 0.02). The 2 groups were at similar risk of hospitalization (52% vs 39%; P = 0. 11). Conclusions: According to parental report, only half of children presenting to the ED with bronchiolitis who met AAP criteria for palivizumab prophylaxis received this monoclonal antibody. Emergency department visits provide an untapped opportunity for staff to educate families and communicate with PCPs about RSV prophylaxis. C1 Childrens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Emergency Med, Boston, MA 02114 USA. RP Mansbach, J (reprint author), Childrens Hosp, Main Clin Bldg 9 S,9157, Boston, MA 02115 USA. EM jonathan.mansbach@childrens.harvard.edu NR 34 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD JUN PY 2007 VL 23 IS 6 BP 362 EP 367 DI 10.1097/01.pec.0000278406.75815.d3 PG 6 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 179YV UT WOS:000247327600002 PM 17572518 ER PT J AU Zhang, SL Chen, YW Tran, S Liu, F Nestoridi, E Hebert, MJ Ingelfinger, JR AF Zhang, Shao-Ling Chen, Yun-Wen Tran, Stella Liu, Fang Nestoridi, Eirini Hebert, Marie-Josee Ingelfinger, Julie R. TI Pax-2 and N-myc regulate epithelial cell proliferation and apoptosis in a positive autocrine feedback loop SO PEDIATRIC NEPHROLOGY LA English DT Article DE Pax-2; N-myc; high glucose and ROS ID PROXIMAL TUBULAR CELLS; RENAL-COLOBOMA SYNDROME; URETERAL BUD APOPTOSIS; DIABETIC COMPLICATIONS; ANGIOTENSINOGEN GENE; KIDNEY DEVELOPMENT; FETAL KIDNEY; EXPRESSION; MICE; NEPHROGENESIS AB Both paired homeo box-2 (Pax-2) and N-myc genes play pivotal roles in renal morphogenesis via their effects on cell proliferation and differentiation, but whether and how they interact have not been addressed. In the present study, we investigated such a potential interaction using embryonic renal cells in vitro. Mouse embryonic mesenchymal (MK4) cells stably transfected with Pax-2 cDNA in sense (+) or antisense (-) orientation were used for experiments. Pax-2 promoter activity was monitored by luciferase assay. Reactive oxygen species (ROS) generation, cell proliferation, and cell apoptosis were evaluated. We found that Pax-2 and N-myc gene expression were upregulated and downregulated in Pax-2 (+) and Pax-2 (-) stable transformants, respectively. ROS generation and apoptosis were significantly reduced both in Pax-2 (+) transformants compared with Pax-2 (-) transformants and in naive MK4 cells cultured in either normal- (5 mM) or high-glucose (25 mM) medium. Transient transfection of N-myc cDNA into Pax-2 (-) stable transformants restored Pax-2 gene expression and prevented ROS generation induced by high glucose. Our data demonstrate that Pax-2 gene overexpression prevents hyperglycemia-induced apoptosis, and N-myc appears to provide a positive autocrine feedback on Pax-2 gene expression in embryonic mesenchymal cells. C1 Univ Montreal, CHUM, Hotel Dieu, Montreal, PQ H2W 1T7, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Zhang, SL (reprint author), Univ Montreal, CHUM, Hotel Dieu, 3850 St Urbain St, Montreal, PQ H2W 1T7, Canada. EM shao.ling.zhang@umontreal.ca NR 49 TC 9 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JUN PY 2007 VL 22 IS 6 BP 813 EP 824 DI 10.1007/s00467-007-0444-z PG 12 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 159GC UT WOS:000245852400008 PM 17357786 ER PT J AU Bogdanov, AA Lin, CP Kang, HW AF Bogdanov, Alexei A., Jr. Lin, Charles P. Kang, Hye-Won TI Optical imaging of the adoptive transfer of human endothelial cells in mice using anti-human CD31 monoclonal antibody SO PHARMACEUTICAL RESEARCH LA English DT Article DE adoptive transfer; CD31; endothelium; fluorescence; molecular imaging; near-infrared; PECAM-1 ID RECONSTITUTED BASEMENT-MEMBRANE; IN-VIVO; BREAST-CANCER; E-SELECTIN; CONTRAST AGENTS; BLOOD-VESSELS; ANGIOGENESIS; EXPRESSION; DIFFERENTIATION; MORPHOGENESIS AB Purpose. The development of endothelium-specific imaging agents capable of specific binding to human cells under the conditions of flow for the needs of regenerative medicine and cancer research. The goal of the study was testing the feasibility of optical imaging of human endothelial cells implanted in mice. Methods. Mouse model of adoptive human endothelial cell transfer was obtained by implanting cells in Matrigel matrix in subcutaneous space (Kang, Torres, Wald, Weissleder, and Bogdanov, Jr., Targeted imaging of human endothelial-specific marker in a model of adoptive cell transfer. Lab. Invest. 86: 599609, 2006). Several endothelium-specific proteins were labeled with near-infrared fluorochrome (Cy5.5) and tested in vitro. Fluorescence imaging using anti-human CD31 antibody was performed in vivo. The obtained results were corroborated by using fluorescence microscopy of tissue sections. Results. We determined that monoclonal anti-human CD31 antibodies labeled with Cy5.5 were efficiently binding to human endothelial cells and were not subject to rapid endocytosis. We further demonstrated that specific near-infrared optical imaging signal was present only in Matrigel implants seeded with human endothelium cells and was absent from control Matrigel implants. Histology showed staining of cells lining vessels and revealed the formation of branched networks of CD31-positive cells. Conclusions. Anti-human CD31 antibodies tagged with near-infrared fluorochromes can be used for detection of perfused blood vessels harboring human endothelial cells in animal models of adoptive transfer. C1 Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, S2-804,55 Lake Ave N, Worcester, MA 01655 USA. EM Alexei.Bogdanov@umassmed.edu FU NIBIB NIH HHS [EB000664, R01 EB000664, R01 EB000664-03, R01 EB000858] NR 31 TC 13 Z9 13 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD JUN PY 2007 VL 24 IS 6 BP 1186 EP 1192 DI 10.1007/s11095-006-9219-7 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 169VH UT WOS:000246619700017 PM 17373582 ER PT J AU Das Evcimen, N King, GL AF Das Evcimen, Net King, George L. TI The role of protein kinase C activation and the vascular complications of diabetes SO PHARMACOLOGICAL RESEARCH LA English DT Review DE protein kinase C (PKC); diabetes mellitus; PKC isoforms; LY333531; rubokxistaurin ID RETINAL BLOOD-FLOW; GROWTH-FACTOR-BETA; GLOMERULAR MESANGIAL CELLS; ELEVATED GLUCOSE-LEVELS; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS; VITAMIN-E SUPPLEMENTATION; MESSENGER-RNA EXPRESSION; SODIUM-POTASSIUM-ATPASE; HUMAN ENDOTHELIAL-CELLS AB Diabetes mellitus is a chronic disease caused by inherited and/or acquired deficiency in production of insulin by the pancreas, and by resistance to insulin's effects. Such a deficiency results in increased concentrations of glucose and other metabolites in the blood, which in turn damages many of the body's systems, in particular the eyes, kidneys, nerves, heart and blood vessels. There are two major types of diabetes mellitus: Type I diabetes (insulin-dependent diabetes, IDDM or juvenile onset diabetes) and Type 2 diabetes (non-insulin-dependent diabetes, NIDDM or adult-onset). Chronic hyperglycemia is a major initiator of diabetic micro- and cardiovascular complications, such as retinopathy, neuropathy and nephropathy. Several hyperglycemia-induced mechanisms may induce vascular dysfunctions, which include increased polyol pathway flux, altered cellular redox state, increased formation of diacylglycerol (DAG) and the subsequent activation of protein kinase C (PKC) isoforms and accelerated non-enzymatic formation of advanced glycated end products. It is likely that each of these mechanisms may contribute to the known pathophysiologic features of diabetic complications. Others and we have shown that activation of the DAG-PKC pathway is associated with many vascular abnormalities in the retinal, renal, neural and cardiovascular tissues in diabetes mellitus. DAG-PKC pathway affects cardiovascular function in many ways, such as the regulation of endothelial permeability, vasoconstriction, extracellular matrix (ECM) synthesis/turnover, cell growth, angiogenesis, cytokine activation and leucocyte adhesion, to name a few. Increased DAG levels and PKC activity, especially a, beta 1/2 and 8 isoforms in retina, aorta, heart, renal glomeruli and circulating macrophages have been reported in diabetes. Increased PKC activation have been associated with changes in blood flow, basement membrane thickening, extracellular matrix expansion, increases in vascular permeability, abnormal angiogenesis, excessive apoptosis and changes in enzymatic activity alterations such as Na+-K+-ATPase, cPLA(2), PI3Kinase and MAP kinase. Inhibition of PKC, especially the beta 1/2 isoform has been reported to prevent or normalize many vascular abnormalities in the tissues described above. Clinical studies have shown that ruboxistaurin, a PKC beta isoform selective inhibitor, normalize endothelial dysfunction, renal glomerular filtration rate and prevented loss of visual acuity in diabetic patients. Thus, PKC activation involving several isoforms is likely to be responsible for some of the pathologies in diabetic retinopathy, nephropathy and cardiovascular disease. PKC isoform selective inhibitors are likely new therapeutics, which can delay the onset or stop the progression of diabetic vascular disease with very little side effects. (C) 2007 Published by Elsevier Ltd. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02030 USA. Ankara Univ, Fac Pharm, Dept Biochem, TR-06100 Ankara, Turkey. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl,Room 4504, Boston, MA 02030 USA. EM george.king@joslin.harvard.edu FU NIDDK NIH HHS [DK07135-02, DK53105-6] NR 169 TC 177 Z9 181 U1 7 U2 32 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD JUN PY 2007 VL 55 IS 6 BP 498 EP 510 DI 10.1016/j.phrs.2007.04.016 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 191VP UT WOS:000248160400005 PM 17574431 ER PT J AU Dempsey, EC Cool, CD Littler, CM AF Dempsey, Edward C. Cool, Carlyne D. Littler, Cassana M. TI Lung disease and PKCs SO PHARMACOLOGICAL RESEARCH LA English DT Review DE pulmonary vasculature; airway; alveolar; interstitial; injury; inflammation; cancer; contraction; proliferation; apoptosis; migration; PKC-alpha; PKC-beta; PKC-delta; PKC-epsilon; PKC-theta; PKC-eta; PKC-zeta; PKC-iota; human; knockout mice ID PROTEIN-KINASE-C; SMOOTH-MUSCLE-CELLS; BRONCHIAL EPITHELIAL-CELLS; FIBROBLAST COLLAGEN-SYNTHESIS; ENDOTHELIAL PROGENITOR CELLS; KAPPA-B ACTIVATION; GROWTH-FACTOR-BETA; GENE-EXPRESSION; PULMONARY-FIBROSIS; CANCER CELLS AB The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Cardiovasc Pulm Res Lab, Denver, CO 80262 USA. Denver VA Med Ctr, Med Serv, Pulm & Crit Care Sect, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Natl Jewish Med & Res Ctr, Dept Med, Denver, CO 80220 USA. RP Dempsey, EC (reprint author), Univ Colorado, Hlth Sci Ctr, Cardiovasc Pulm Res Lab, B-133,4200 E 9th Ave, Denver, CO 80262 USA. EM edward.dempsey@uchsc.edu FU NHLBI NIH HHS [HL14985, R0-1 HL078927]; NIDDK NIH HHS [5 T35 DK07496-18] NR 112 TC 50 Z9 53 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-6618 J9 PHARMACOL RES JI Pharmacol. Res. PD JUN PY 2007 VL 55 IS 6 BP 545 EP 559 DI 10.1016/j.phrs.2007.04.010 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 191VP UT WOS:000248160400009 PM 17582782 ER PT J AU Benator, DA Weiner, MH Burman, WJ Vernon, AA Zhao, ZA Khan, AE Jones, BE Sandman, L Engle, M Silva-Trigo, C Hsyu, PH Becker, MI Peloquin, CA AF Benator, Debra A. Weiner, Marc H. Burman, William J. Vernon, Andrew A. Zhao, Zhen A. Khan, Awal E. Jones, Brenda E. Sandman, Laurie Engle, Melissa Silva-Trigo, Claudia Hsyu, Poe H. Becker, Mark I. Peloquin, Charles A. CA Tuberculosis Trials Consortium TI Clinical evaluation of the nelfinavir-rifabutin interaction in patients with tuberculosis and human immunodeficiency virus infection SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 100th International Conference of the American-Thoracic-Society CY MAY 21-26, 2004 CL Orlando, FL SP Amer Thorac Soc DE tuberculosis; human immunodeficiency virus; HIV; nelfinavir; rifabutin; isoniazid; drug interactions; cytochrome P450; pharmacokinetics ID ACQUIRED RIFAMYCIN RESISTANCE; PHARMACOKINETICS; HIV; PLASMA; M8 AB Study Objective. To characterize the bidirectional interaction between twice-daily nelfinavir and twice-weekly rifabutin and isoniazid in patients with tuberculosis and human immunodeficiency virus (HIV) infection. Design. Prospective cohort study. Setting. Three clinical research centers. Patients. Seven patients with HIV-related tuberculosis. Intervention. Rifabutin 300 mg and isoniazid 15 mg/kg (maximum dose 900 mg) twice/week were administered for at least 2 weeks during the continuation phase of tuberculosis treatment. Antiretroviral therapy with nelfinavir 1250 mg twice/day and two nucleoside reverse transcriptase inhibitors was then added. Measurements and Main Results. Patients underwent blood sampling for pharmacokinetic analysis during the continuation phase of tuberculosis therapy and after a median of 21, days after the addition of antiretroviral treatment. When rifabutin was coadministered with nelfinavir, its area under the concentration-time curve from 0-21 hours (AUC(0-21)) increased 22% (geometric mean 5.01 mu g.hr/ml [90% confidence interval (CI) 3.25-7.711 with nelfinavir vs 4.10 mu g.hr/ml [90% CI 3.18-5.27] without nelfinavir; geometric mean ratio 1.22 [90% CI 0.78-1.921). Also, the AUCO-21 for the active metabolite, desacetylrifabutin, increased significantly (geometric mean ratio 3.46, 90% CI 1.84-6.47, p=0.009). in the presence of rifabutin, the pharmacokinetic parameters of nelfinavir and its principal metabolite M8 were similar to those of patients not taking rifabutin. No drug interaction between nelfinavir and isoniazid was detected. Conclusions. Coadministration of rifabutin and isoniazid without dosage adjustment during twice-weekly tuberculosis therapy with nelfinavir-based antiretroviral therapy resulted in rifabutin exposures within the acceptable ranges for safety and efficacy. Therefore, this combination is an appropriate option for the simultaneous treatment of tuberculosis and HIV infection when tuberculosis therapy is given twice weekly. C1 Vet Affairs Med Ctr, Div Infect Dis, Washington, DC 20422 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. NYU, Sch Med, New York, NY USA. Agouron Pharmaceut Inc, La Jolla, CA USA. RP Benator, DA (reprint author), Vet Affairs Med Ctr, Div Infect Dis, 151 B,50 Irving St NW, Washington, DC 20422 USA. EM debra.benator@med.va.gov FU NCRR NIH HHS [M01-RR-01346] NR 28 TC 10 Z9 11 U1 2 U2 7 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUN PY 2007 VL 27 IS 6 BP 793 EP 800 DI 10.1592/phco.27.6.793 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 172OF UT WOS:000246812900003 PM 17542762 ER PT J AU Dupin, MM Halliday, I Care, CM Alboul, L Munn, LL AF Dupin, Michael M. Halliday, Ian Care, Chris M. Alboul, Lyuba Munn, Lance L. TI Modeling the flow of dense suspensions of deformable particles in three dimensions SO PHYSICAL REVIEW E LA English DT Article ID RED-BLOOD-CELLS; LATTICE BOLTZMANN METHOD; OPTICAL TWEEZERS; SHEAR-FLOW; POSTCAPILLARY EXPANSIONS; PARTICULATE SUSPENSIONS; BOUNDARY-CONDITION; CAPILLARY VESSELS; SIMULATIONS; FLUID AB We describe here a rigorous and accurate model for the simulation of three-dimensional deformable particles (DPs). The method is very versatile, easily simulating various types of deformable particles such as vesicles, capsules, and biological cells. Each DP is resolved explicitly and advects within the surrounding Newtonian fluid. The DPs have a preferred rest shape (e.g., spherical for vesicles, or biconcave for red blood cells). The model uses a classic hybrid system: an Eulerian approach is used for the Navier-Stokes solver (the lattice Boltzmann method) and a Lagrangian approach for the evolution of the DP mesh. Coupling is accomplished through the lattice Boltzmann velocity field, which transmits force to the membranes of the DPs. The novelty of this method resides in its ability (by design) to simulate a large number of DPs within the bounds of current computational limitations: our simple and efficient approach is to (i) use the lattice Boltzmann method because of its acknowledged efficiency at low Reynolds number and its ease of parallelization, and (ii) model the DP dynamics using a coarse mesh (approximately 500 nodes) and a spring model constraining (if necessary) local area, total area, cell volume, local curvature, and local primary stresses. We show that this approach is comparable to the more common-yet numerically expensive-approach of membrane potential function, through a series of quantitative comparisons. To demonstrate the capabilities of the model, we simulate the flow of 200 densely packed red blood cells-a computationally challenging task. The model is very efficient, requiring of the order of minutes for a single DP in a 50 mu mx40 mu mx40 mu m simulation domain and only hours for 200 DPs in 80 mu mx30 mu mx30 mu m. Moreover, the model is highly scalable and efficient compared to other models of blood cells in flow, making it an ideal and unique tool for studying blood flow in microvessels or vesicle or capsule flow (or a mixture of different particles). In addition to directly predicting fluid dynamics in complex suspension in any geometry, the model allows determination of accurate, empirical rules which may improve existing macroscopic, continuum models. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Steele Lab, Boston, MA 02114 USA. Sheffield Hallam Univ, Mat & Engn Res Inst, Sheffield S1 1WB, S Yorkshire, England. RP Dupin, MM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Steele Lab, Boston, MA 02114 USA. EM mdupin@steele.mgh.harvard.ed; i.halliday@shu.ac.uk; c.m.care@shu.ac.uk; lance@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Care, Christopher/0000-0003-2592-5280 FU NCI NIH HHS [R21 CA126761, R21 CA126761-01, R21 CA126761-02]; NHLBI NIH HHS [R01 HL064240, R01 HL064240-07, R01 HL064240-08] NR 58 TC 145 Z9 145 U1 3 U2 38 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD JUN PY 2007 VL 75 IS 6 AR 066707 DI 10.1103/PhysRevE.75.066707 PN 2 PG 17 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 184EO UT WOS:000247624100078 PM 17677389 ER PT J AU Coffin-Zadai, CA AF Coffin-Zadai, Cynthia A. TI Disabling our diagnostic dilemmas SO PHYSICAL THERAPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Physical-Therapy-Association CY JUL 01, 2004 CL Chicago, IL SP Amer Phys Therapy Assoc ID LOW-BACK-PAIN; CLINICAL-PRACTICE GUIDELINES; PHYSICAL-THERAPY; CLASSIFICATION APPROACH; SPECIAL COMMUNICATION; RELIABILITY AB The physical therapy profession's diagnostic dilemma results from its confused response to competing issues that affect the physical therapist's role as a diagnostician. The major components of the diagnostic dilemma are: (1) the competition among new ideas, (2) the complexity of the diagnostic process and language used to describe the outcome, (3) the profession's lack of consensus regarding the diagnostic classification construct to be embraced, and (4) the rapid evolution and impact of new knowledge. The interaction of these 4 components results in "diagnostic disablement." Whether managing a patient, creating a curriculum to educate new physical therapy practitioners, or applying for research funding to study the science or practice of diagnostic classification, physical therapists face a real challenge in understanding and complying with all the current diagnostic requirements of the US health care system and the physical therapy profession. This article traces the 4 components and considers the strategies the profession can use to resolve its diagnostic dilemma. The first step would be to standardize the language that physical therapists use to describe or diagnose phenomena within their scope of practice. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Grad Programs Phys Therapy, Phys Therapy Program, Boston, MA 02129 USA. RP Coffin-Zadai, CA (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Programs Phys Therapy, Phys Therapy Program, Boston, MA 02129 USA. EM czadai@mghihp.edu NR 30 TC 16 Z9 18 U1 0 U2 1 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD JUN PY 2007 VL 87 IS 6 BP 641 EP 653 DI 10.2522/ptj.20060236 PG 13 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 174ZU UT WOS:000246982400004 PM 17504825 ER PT J AU Valdiserri, RO AF Valdiserri, Ronald O. TI Late HIV diagnosis: Bad medicine and worse public health SO PLOS MEDICINE LA English DT Editorial Material ID PERSONS AWARE; UNITED-STATES; PREVENTION; INFECTION; UNAWARE; VIRUS C1 US Dept Vet Affairs, Washington, DC USA. RP Valdiserri, RO (reprint author), US Dept Vet Affairs, Washington, DC USA. EM R.Valdiserri@va.gov NR 14 TC 19 Z9 19 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JUN PY 2007 VL 4 IS 6 BP 975 EP 976 AR e200 DI 10.1371/journal.pmed.0040200 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 182AA UT WOS:000247476300005 PM 17564489 ER PT J AU Wagner, CR Stylopoulos, N Jackson, PG Howe, RD AF Wagner, Christopher R. Stylopoulos, Nicholas Jackson, Patrick G. Howe, Robert D. TI The benefit of force feedback in surgery: Examination of blunt dissection SO PRESENCE-TELEOPERATORS AND VIRTUAL ENVIRONMENTS LA English DT Article; Proceedings Paper CT 10th Symposium on Haptic Interfaces for Virtual Environment and Teleoperator Systems (HAPTICS 2002) CY MAR 24-25, 2002 CL ORLANDO, FL SP IEEE Comp Soc ID CORONARY-ARTERY-BYPASS; ENDOSCOPIC GRASPER; PERFORMANCE; TELEMANIPULATION; SENSOR AB Force feedback is widely assumed to enhance performance in robotic surgery, but its benefits have not yet been systematically assessed. In this study we examine the effects of force feedback on a blunt dissection task. Twenty subjects used a tele-robotic system to expose an artery in a synthetic model while viewing the operative site with a video laparoscope. Subjects were drawn from a range of surgical backgrounds, from inexperienced to attending surgeons. Performance was compared between three force feedback gains: 0% (no force feedback), 37%, and 75%. The absence of force feedback increased the average force magnitude applied to the tissue by at least 50%, and increased the peak force magnitude by at least 100%, The number of errors that damage tissue increased by over a factor of 3. The rate and precision of dissection were not significantly enhanced with force feedback. These results hold across all levels of previous surgical experience. We hypothesize that force feedback is helpful in this blunt dissection task because the artery is stiffer than the surrounding tissue. This mechanical contrast serves to constrain the subject's hand from commanding inappropriate motions that generate large forces. C1 Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Georgetown Univ Hosp, Dept Surg, Washington, DC 20007 USA. RP Wagner, CR (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM cwagner@post.harvard.edu NR 26 TC 58 Z9 61 U1 0 U2 2 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 1054-7460 EI 1531-3263 J9 PRESENCE-TELEOP VIRT JI Presence-Teleoper. Virtual Env. PD JUN PY 2007 VL 16 IS 3 BP 252 EP 262 DI 10.1162/pres.16.3.252 PG 11 WC Computer Science, Cybernetics; Computer Science, Software Engineering SC Computer Science GA 170LO UT WOS:000246665100003 ER PT J AU Fagan, A Culhane, AC Higgins, DG AF Fagan, Ailis Culhane, Aedin C. Higgins, Desmond G. TI A multivariate analysis approach to the integration of proteomic and gene expression data SO PROTEOMICS LA English DT Article DE co-inertia analysis; data integration; gene ontology; microarray ID PROTEIN IDENTIFICATION TECHNOLOGY; CO-INERTIA ANALYSIS; CANCER-CELL LINES; SACCHAROMYCES-CEREVISIAE; MICROARRAY DATA; LIFE-CYCLE; PLASMODIUM-FALCIPARUM; MASS-SPECTROMETRY; SYSTEMS BIOLOGY; MESSENGER-RNA AB In order to understand even the simplest cellular processes, we need to integrate proteomic, gene expression and other biomolecular data. To date, most computational approaches aimed at integrating proteomics and gene expression data use direct gene/protein correlation measures. However, due to post-transcriptional and translational regulations, the correspondence between the expression of a gene and its protein is complicated. We apply a multivariate statistical method, co-inertia analysis (CIA), to visualise gene and proteomic expression data stemming from the same biological samples. Principal components analysis or correspondence analysis can be used for data exploration on single datasets. CIA is then used to explore the relationships between two or more datasets. We further explore the data by projecting gene ontology (GO) information onto these plots to describe the cellular processes in action. We apply these techniques to gene expression and protein abundance data from studies of the human malarial parasite life cycle and the NCI-60 cancer cell lines. In each case, we visualise gene expression, protein abundance and GO classes in the same low dimensional projections and identify GO classes that are likely to be of biological importance. C1 Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Fagan, A (reprint author), Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland. EM Ailis.Fagan@ucd.ie RI Higgins, des/J-6314-2012; OI Higgins, Des/0000-0002-3952-3285 NR 57 TC 45 Z9 48 U1 2 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD JUN PY 2007 VL 7 IS 13 BP 2162 EP 2171 DI 10.1002/pmic.200600898 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 189UJ UT WOS:000248013700004 PM 17549791 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. TI A counter proposal to manage financial conflicts of interest in academic psychiatry SO PSYCHIATRIA DANUBINA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-5053 J9 PSYCHIAT DANUB JI Psychiatr. Danub. PD JUN PY 2007 VL 19 IS 1-2 BP 111 EP 112 PG 2 WC Psychiatry SC Psychiatry GA 270GV UT WOS:000253710100023 ER PT J AU Cusack, KJ Grubaugh, AL Yim, E Knapp, RG Robins, CS Frueh, BC AF Cusack, Karen J. Grubaugh, Anouk L. Yim, Eunsil Knapp, Rebecca G. Robins, Cynthia S. Frueh, B. Christopher TI Are there racial differences in the experience of harmful or traumatic events within psychiatric settings? SO PSYCHIATRIC QUARTERLY LA English DT Article DE psychiatric patients; hospital; racial differences; trauma ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-ILLNESS; PSYCHOMETRIC PROPERTIES; SPECIAL SECTION; PTSD CHECKLIST; CARE; RESTRAINT; SECLUSION; RACE; SCHIZOPHRENIA AB The current study examined racial differences in the reported frequency and distress associated with potentially harmful or traumatic experiences occurring within psychiatric settings. One hundred and forty-two (109 African-American; 32 Caucasian) randomly selected adult consumers recruited from a community psychosocial day program completed a battery of self-report measures to assess experiences in the psychiatric setting, lifetime trauma exposure, PTSD severity, and were the subject of a chart review. A subset of participants (20%) also completed a qualitative interview exploring their perceptions of events occurring in psychiatric settings. Few racial differences were noted in the reported frequency or distress associated with particular events in the psychiatric setting. However, we found differential patterns of association between adverse psychiatric events and lifetime trauma history, and racial differences in diagnosis and medications prescribed by the mental health center. These racial differences merit further attention to better understand their meaning and to improve mental health services provided to both African-Americans and Caucasian public-sector psychiatric patients. C1 Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC USA. Westat Corp, Rockville, MD USA. Univ Hawaii, Dept Psychol, Hilo, HI USA. RP Cusack, KJ (reprint author), Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, 725 Martin Luther King,CB 7590, Chapel Hill, NC 27599 USA. EM kcusack@schsr.unc.edu FU NIMH NIH HHS [MH01660, MH65517] NR 42 TC 5 Z9 5 U1 2 U2 5 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0033-2720 J9 PSYCHIAT QUART JI Psychiatr. Q. PD JUN PY 2007 VL 78 IS 2 BP 101 EP 115 DI 10.1007/s11126-006-9031-x PG 15 WC Psychiatry SC Psychiatry GA 157ZH UT WOS:000245759700003 PM 17345158 ER PT J AU Grubaugh, AL Resick, PA AF Grubaugh, Anouk L. Resick, Patricia A. TI Posttraumatic growth in treatment-seeking female assault victims SO PSYCHIATRIC QUARTERLY LA English DT Article DE posttraumatic growth; perceived benefits; posttraumatic stress disorder (PTSD); trauma ID CHILD SEXUAL ABUSE; STRESS-DISORDER; PERCEIVED BENEFIT; BREAST-CANCER; SURVIVORS; COMORBIDITY; BEREAVEMENT; ADVERSITY; EXPOSURE; SEARCH AB The importance of measuring growth outcomes following a traumatic event has been highlighted in recent literature (e.g., Linley, Joseph: Journal of Traumatic Stress 17:11-21, 2004). Although reports of growth are abundant, the relationship between growth outcomes and post-trauma distress remains unclear, with studies yielding conflicting results regarding this relationship. The purpose of the present study was to explore the interrelationships among growth outcomes and measures of depression and posttraumatic stress disorder (PTSD) among 100 female treatment-seeking physical and sexual assault victims. Although the majority of women reported some degree of growth in this study, and growth scores were comparable to those from other samples, measures of depression and PTSD were not significantly related to growth scores. The implication of these findings and future direction for research are discussed. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Div Publ Psychiat, Charleston, SC 29425 USA. Univ Missouri, Ctr Trauma Recovery, St Louis, MO USA. Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. Boston Univ, Boston, MA USA. Ralph H Johnson Vet Affaris Med Ctr, Charleston, SC USA. RP Grubaugh, AL (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Div Publ Psychiat, POB 2508561, Charleston, SC 29425 USA. EM grubaugh@musc.edu FU NIMH NIH HHS [R01 MH051509, R01 MH051509-10, R01-MH51509] NR 45 TC 28 Z9 29 U1 2 U2 9 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0033-2720 J9 PSYCHIAT QUART JI Psychiatr. Q. PD JUN PY 2007 VL 78 IS 2 BP 145 EP 155 DI 10.1007/s11126-006-9034-7 PG 11 WC Psychiatry SC Psychiatry GA 157ZH UT WOS:000245759700006 PM 17380387 ER PT J AU Zeber, JE McCarthy, JF Bauer, MS Kilbourne, AM AF Zeber, John E. McCarthy, John F. Bauer, Mark S. Kilbourne, Amy M. TI Datapoints: Self-reported access to general medical and psychiatric care among veterans with bipolar disorder SO PSYCHIATRIC SERVICES LA English DT Editorial Material C1 [Zeber, John E.] S Texas Vet Hlth Care Syst, Vet Affairs Hlth Serv Res & Dev Serv, San Antonio, TX 78229 USA. [McCarthy, John F.; Kilbourne, Amy M.] VA HSR&D, Serious Ment Illness Treatment Evaluat & Res Ctr, Ann Arbor, MI USA. [Bauer, Mark S.] VA Med Ctr, Providence, RI USA. RP Zeber, JE (reprint author), S Texas Vet Hlth Care Syst, Vet Affairs Hlth Serv Res & Dev Serv, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78229 USA. EM zeber@uthscsa.edu NR 3 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUN PY 2007 VL 58 IS 6 BP 740 EP 740 DI 10.1176/appi.ps.58.6.740 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 265LJ UT WOS:000253360100002 PM 17535932 ER PT J AU Kring, AM Sloan, DM AF Kring, Ann M. Sloan, Denise M. TI The Facial Expression Coding System (FACES): Development, validation, and utility SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE emotion; facial expression; EMG; FACES ID POSTTRAUMATIC-STRESS-DISORDER; SCHIZOPHRENIC-PATIENTS SHOW; SELF-REPORT; EMOTIONAL EXPRESSIVITY; SUBJECTIVE EXPERIENCE; FLAT AFFECT; PHYSIOLOGY; DEPRESSION; BEHAVIOR; WOMEN AB This article presents information on the development and validation of the Facial Expression Coding System (FACES; A. M. Kring & D. Sloan, 199 1). Grounded in a dimensional model of emotion, FACES provides information on the valence (positive, negative) of facial expressive behavior. In 5 studies, reliability and validity data from 13 diverse samples, including students, psychiatric patients, and community adults, are presented, and results indicate that raters can reliably agree on instances of positive and negative expressive behavior. Validity studies indicate that FACES ratings are related in predictable ways to another observational coding system, facial muscle activity, individual-difference measures of expressiveness and personality, skin conductance, heart rate, and reports of experienced emotion. FACES can be a useful tool for assessing expressive behavior in a variety of contexts. C1 Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Kring, AM (reprint author), Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA. EM akring@berkeley.edu; denise.sloan@va.gov OI Sloan, Denise/0000-0002-0962-478X NR 92 TC 38 Z9 39 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD JUN PY 2007 VL 19 IS 2 BP 210 EP 224 DI 10.1037/1040-3590.19.2.210 PG 15 WC Psychology, Clinical SC Psychology GA 176KM UT WOS:000247083900005 PM 17563202 ER PT J AU Senior, AC Kunik, ME Rhoades, HM Novy, DM Wilson, NL Stanley, MA AF Senior, Ashley C. Kunik, Mark E. Rhoades, Howard M. Novy, Diane M. Wilson, Nancy L. Stanley, Melinda A. TI Utility of telephone assessments in an older adult population SO PSYCHOLOGY AND AGING LA English DT Article DE telephone assessments; anxiety and depression; older adults ID MULTITRAIT-MULTIMETHOD MATRIX; GENERALIZED ANXIETY DISORDER; BECK DEPRESSION INVENTORY; FACE-TO-FACE; PRIMARY-CARE; VALIDATION; INTERVIEW; OUTCOMES; IMPACT; SCALE AB Telephone assessments are commonly used in mental health research and may be especially beneficial in older populations. The current study assessed the psychometric properties of the Penn State Worry Questionnaire (T. J. Meyer, M. L. Miller, R. L. Metzger, & T. D. Borkovec, 1990) and the Beck Depression Inventory-II (A. T. Beck, R. A. Steer, & G. K. Brown, 1996), when administered over the telephone in an older adult population. Results indicate no differences in mean symptom level or internal consistency across two modes of administration. Correlations between the in-person and telephone-administered measures and diagnostic categories suggest adequate validity of the telephone-administered measures. With this demonstrated evidence, the telephone assessment method can be applied in a variety of research and clinical settings. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. Univ Houston, Dept Psychol, Houston, TX 77004 USA. Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Houston, TX 77225 USA. RP Stanley, MA (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM mstanley@bcm.tmc.edu FU PHS HHS [53932] NR 43 TC 18 Z9 18 U1 20 U2 21 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD JUN PY 2007 VL 22 IS 2 BP 392 EP 397 DI 10.1037/0882-7974.22.2.392 PG 6 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 176KI UT WOS:000247083500019 PM 17563195 ER PT J AU Bullain, SS Chriki, LS Stern, TA AF Bullain, Szofia S. Chriki, Lyvia S. Stern, Theodore A. TI Aphasia: Associated disturbances in affect, behavior, and cognition in the setting of speech and language difficulties SO PSYCHOSOMATICS LA English DT Article ID DEPRESSION QUESTIONNAIRE; STROKE; THERAPY; REHABILITATION; BROMOCRIPTINE; IMPAIRMENT; RECOVERY AB Patients with disturbances in affect, behavior, and cognition present a variety of challenges to healthcare providers; their evaluation and treatment becomes especially problematic in the setting of speech and language difficulties. The authors present the case of a man who sustained a left-side cerebrovascular accident with aphasia and discuss the approach to his diagnosis and treatment. Moreover, since a variety of speech and language problems can arise after stroke and since patients and their treaters can become frustrated by impaired communication and diagnostic uncertainties, authors review the clinical manifestations, timing, and treatment of such conditions so that treatment can be improved. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat Consultat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Bullain, SS (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, EDR 410,70 Blossom St, Boston, MA 02114 USA. EM SBullain@Partners.org NR 40 TC 2 Z9 2 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUN PY 2007 VL 48 IS 3 BP 258 EP 264 DI 10.1176/appi.psy.48.3.258 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 164CN UT WOS:000246210400011 PM 17478596 ER PT J AU Thrall, JH AF Thrall, James H. TI Teleradiology - Part I. History and clinical applications SO RADIOLOGY LA English DT Editorial Material ID REINVENTING RADIOLOGY; DIGITAL-AGE C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZ-FND 216,Box 9657,14 Fruit St, Boston, MA 02114 USA. EM thrall.james@mgh.harvard.edu NR 12 TC 42 Z9 42 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2007 VL 243 IS 3 BP 613 EP 617 DI 10.1148/radiol.2433070350 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 170UQ UT WOS:000246691600002 PM 17517922 ER PT J AU Ferencik, M Ropers, D Abbara, S Cury, RC Hoffmann, U Nieman, K Brady, TJ Moselewski, F Daniel, WG Achenbach, S AF Ferencik, Maros Ropers, Dieter Abbara, Suhny Cury, Ricardo C. Hoffmann, Udo Nieman, Koen Brady, Thomas J. Moselewski, Fabian Daniel, Werner G. Achenbach, Stephan TI Diagnostic accuracy of image postprocessing methods for the detection of coronary artery stenoses by using multidetector CT SO RADIOLOGY LA English DT Article ID SPIRAL COMPUTED-TOMOGRAPHY; ELECTRON-BEAM CT; ANGIOGRAPHY; RECONSTRUCTION; MULTIPLANAR; RESOLUTION AB Purpose: To retrospectively evaluate the diagnostic accuracy of .multidetector computed tomography ( CT) coronary angiography for detection of hemodynamically significant ( >= 50%) stenoses by using various image postprocessing methods, with conventional coronary angiography as the reference standard. Materials and Methods: The analysis used data from previous studies, use of which had been approved by the Institutional Review Board. Sixteen-section multidetector CT data sets for 40 patients ( 30 men, 10 women; mean age 56 years +/- 8; mean heart rate, 61 beats per minute +/- 6) were evaluated. Six independent investigators evaluated the data sets for the presence of stenoses with diameter reduction of 50% or more, by using either exclusively transverse images, free oblique multiplanar reconstructions ( MPRs), free oblique maximum intensity projections ( MIPs, 5 mm thick), prerendered curved MPRs, prerendered curved MIPs, or prerendered three-dimensional volume rendered reconstructions ( VRTs). Evaluation results were compared with conventional coronary angiography for each artery in a blinded fashion ( chi(2) test). Results: Overall, 35 coronary artery stenoses were present. Percentage of evaluable arteries and accuracy for detecting stenosis ( percentages of accurately classified arteries were, respectively, 99% and 88% for transverse, 99% and 91% for oblique MPR, 94% and 86% for oblique MIP, 94% and 83% for curved MIP, 93% and 81% for curved MPR, and 91% and 73% for VRT). Accuracy was significantly higher for oblique MPR than for curved MPR ( P = .01), curved MIP ( P = .03), and VRT ( P < .001). Conclusion: The evaluation of multidetector CT coronary angiography with interactive image display methods, especially interactive oblique MPRs, permits higher diagnostic accuracy than evaluation of prerendered images ( curved MPR, curved MIP, or VRT images). (c) RSNA, 2007. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Erlangen Nurnberg, Dept Internal Med 2, D-91054 Erlangen, Germany. RP Abbara, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM stephan.achenbach@med2.med.uni-erlangen.de FU NHLBI NIH HHS [1 T32 HL076136-02] NR 27 TC 53 Z9 55 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2007 VL 243 IS 3 BP 696 EP 702 DI 10.1148/radiol.2433060080 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 170UQ UT WOS:000246691600012 PM 17517929 ER PT J AU Sahani, DV Holalkere, NS Mueller, PR Zhu, AX AF Sahani, Dushyant V. Holalkere, Nagaraj-Setty Mueller, Peter R. Zhu, Andrew X. TI Advanced hepatocellular carcinoma: CT perfusion of liver and tumor tissue - Initial experience SO RADIOLOGY LA English DT Article; Proceedings Paper CT 91st Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 27-DEC 02, 2005 CL Chicago, IL SP Radiol Soc N Amer ID COMPUTED-TOMOGRAPHY; RECTAL-CANCER; BLOOD-FLOW; HELICAL CT; ANGIOGENESIS; PERMEABILITY; BEVACIZUMAB; PARENCHYMA AB Purpose: To prospectively assess computed tomographic ( CT) perfusion for evaluation of tumor vascularity of advanced hepatocellular carcinoma ( HCC) and to correlate CT perfusion parameters with tumor grade and serum markers. Materials and Methods: The study was HIPAA compliant and was approved by the institutional review board. Patients provided informed consent. Thirty patients ( 22 men, eight women; mean age, 60 years; range, 28-79 years) with unresectable or metastatic HCC were studied. Dynamic first-pass CT perfusion was performed in primary ( n = 25) and metastatic ( n = 5) HCCs after intravenous injection of contrast medium. Data were analyzed to calculate tissue blood flow, blood volume, mean transit time, and permeability-surface area product. Repeat examination was performed in four patients within 30 hours to test reproducibility of CT perfusion. CT perfusion parameters were compared among tumors of different grades, with presence or absence of portal vein invasion, with presence or absence of cirrhosis, and of various extrahepatic metastases. Parameters were correlated with HCC serum markers. One-way analysis of variance was used to calculate variations in CT perfusion parameters. Results: Good correlation ( r = 0.9, P <= .01) was observed between repeat examination results and first CT examination results. There was a significant difference ( P <= .05) in CT perfusion parameters between primary HCC and background liver parenchyma. Well-differentiated HCC showed significantly higher perfusion values ( P <= .05) than other grades. There was no significant difference in tumor perfusion between presence or absence of portal vein invasion or cirrhosis. Lymph node metastasis demonstrated lower values compared with metastases from other extrahepatic sites. There was no significant correlation between CT perfusion parameters and serum markers. Conclusion: Results suggest that CT perfusion is a feasible and, from the limited data, reproducible technique for quantifying tumor vascularity and angiogenesis in advanced HCC. (c) RSNA, 2007. C1 Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org OI Holalkere, Nagaraj/0000-0001-6324-7682 NR 20 TC 174 Z9 194 U1 1 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2007 VL 243 IS 3 BP 736 EP 743 DI 10.1148/radiol.2433052020 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 170UQ UT WOS:000246691600017 PM 17517931 ER PT J AU Stone, ME AF Stone, Martha E. TI UXL graphic novelists: Profiles of cutting edge authors and illustrators. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD SUM PY 2007 VL 46 IS 4 BP 92 EP 93 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 179LP UT WOS:000247291400035 ER PT J AU Murphy, MR Escamilla, MI Blackwell, PH Lucke, KT Miner-Williams, D Shaw, V Lewis, SL AF Murphy, Margaret R. Escamilla, Monica I. Blackwell, Paula H. Lucke, Kathy T. Miner-Williams, Denise Shaw, Virginia Lewis, Sharon L. TI Focus on research methods - Assessment of caregivers' willingness to participate in an intervention research study SO RESEARCH IN NURSING & HEALTH LA English DT Article DE recruitment; retention; caregivers; Alzheimer's disease; qualitative research ID FAMILY CAREGIVERS; CLINICAL-RESEARCH; RECRUITMENT; RETENTION; DEMENTIA; ISSUES; ADULTS AB The purpose of the study was to identify factors that influenced family caregivers' decisions to participate in an intervention research study. In interviews conducted before and after the intervention, caregivers (n=21) described reasons for participation. A focused content analysis was used to examine responses. Themes that emerged included: (a) caregivers recognized a need for help; (b) expectations and motivations toward change; (c) recognition of self worth as caregivers; (d) timeliness of recruitment strategies; (e) support of research staff affected recruitment; and (f) caregivers recognized the benefits of participation. These findings support the importance of many different strategies for effective recruitment of caregivers in future studies. Copyright (c) 2007 Wiley Periodicals, Inc. C1 S Texas Vet Hlth Care Syst, GRECC 182, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Sch Nursing, San Antonio, TX 78285 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Texas, Hlth Sci Ctr, Sch Med, San Antonio, TX USA. RP Lewis, SL (reprint author), S Texas Vet Hlth Care Syst, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. NR 24 TC 20 Z9 20 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD JUN PY 2007 VL 30 IS 3 BP 347 EP 355 DI 10.1002/nur.20186 PG 9 WC Nursing SC Nursing GA 174JW UT WOS:000246939200011 PM 17514708 ER PT J AU Hoo, GWS AF Hoo, Guy W. Soo TI Hospital at home: The right place for the right patient SO RESPIRATORY CARE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; OBSTRUCTIVE PULMONARY-DISEASE; ACUTE EXACERBATIONS; CARE; OUTCOMES; COPD C1 Univ Calif Los Angeles, Pulm & Crit Care Sect, W Los Angeles Vet Affairs Med Ctr, Vet Affairs Greater Los Angeles Healthcare Syst,G, Los Angeles, CA 90073 USA. RP Hoo, GWS (reprint author), Univ Calif Los Angeles, Pulm & Crit Care Sect, W Los Angeles Vet Affairs Med Ctr, Vet Affairs Greater Los Angeles Healthcare Syst,G, 11301 Wilshire Blvd 111Q, Los Angeles, CA 90073 USA. EM guy.soohoo@va.gov NR 18 TC 0 Z9 0 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD JUN PY 2007 VL 52 IS 6 BP 710 EP 712 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 179KX UT WOS:000247289500001 PM 17521459 ER PT J AU Chipman, DW Caramez, MP Miyoshi, E Kratohvil, JP Kacmarek, RM AF Chipman, Daniel W. Caramez, Maria P. Miyoshi, Eriko Kratohvil, Joseph P. Kacmarek, Robert M. TI Performance comparison of 15 transport ventilators SO RESPIRATORY CARE LA English DT Article DE transport; mechanical ventilation; ventilator; positive end-expiratory pressure; PEEP; fraction of inspired oxygen; F-IO2 ID CRITICALLY-ILL PATIENTS; INTRAHOSPITAL TRANSPORT; BLOOD-GASES AB BACKGROUND: Numerous mechanical ventilators are designed and marketed for use in patient transport. The complexity of these ventilators differs considerably, but very few data exist to compare their operational capabilities. METHODS: Using bench and animal models, we studied 15 currently available transport ventilators with regard to their physical characteristics, gas consumption (duration of an E-size oxygen cylinder), battery life, ease of use, need for compressed gas, ability to deliver set ventilation parameters to a test lung under 3 test conditions, and ability to maintain ventilation and oxygenation in normal and lung-injured sheep. RESULTS: Most of the ventilators tested were relatively simple to operate and had clearly marked controls. Oxygen cylinder duration ranged from 30 min to 77 min. Battery life ranged from 70 min to 8 hours. All except 3 of the ventilators were capable of providing various F-IO2 values. Ten of the ventilators had high-pressure and patient-disconnect alarms. Only 6 of the ventilators were able to deliver all settings as specifically set on the ventilator during the bench evaluation. Only 4 of the ventilators were capable of maintaining ventilation, oxygenation, and hemodynamics in both the normal and the lung-injured sheep. CONCLUSIONS: Only 2 of the ventilators met all the trial targets in all the bench and animal tests. With many of the ventilators, certain of the set ventilation parameters were inaccurate (differed by > 10% from the values from a cardiopulmonary monitor). The physical characteristics and high gas consumption of some of these ventilators may render them less desirable for patient transport. C1 Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 14 TC 20 Z9 20 U1 0 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD JUN PY 2007 VL 52 IS 6 BP 740 EP 751 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 179KX UT WOS:000247289500006 PM 17521464 ER PT J AU Schwartzmann, AM Amaral, JA Issler, C Caetano, SC Tamada, RS de Almeida, KM Soares, MBD Dias, RD Rocca, CC Lafer, S AF Schwartzmann, Angela Maria Amaral, Jose Antonio Issler, Cilly Caetano, Sheila C. Tamada, Renata S. de Almeida, Karla Mathias de Macedo Soares, Marcia Brito da Silva Dias, Rodrigo Rocca, Cristiana C. Lafer, Seny TI A clinical study comparing manic and mixed episodes in patients with bipolar disorder SO REVISTA BRASILEIRA DE PSIQUIATRIA LA English DT Article ID DYSPHORIC MANIA; DEPRESSIVE-MANIA; PANIC DISORDER; PURE-MANIA; SUICIDALITY; STATES; PHENOMENOLOGY; PICTURE AB Objective: Mixed episodes have been described as more severe than manic episodes, especially due to their longer duration and their association with higher rates of suicide attempts, hospitalization and psychotic symptoms. The purpose of this study was to compare the severity between mixed and pure manic episodes according to DSM-1V criteria, through the evaluation of sociodemographic data and clinical characteristics. Method: Twenty-nine bipolar I patients presenting acute mixed episodes were compared to 20 bipolar I patients with acute manic episodes according to DSM-1V criteria. We analyzed (cross-sectionally) episode length, presence of psychotic symptoms, frequency of suicide attempts and hospitalization, Young Mania Rating Scale scores, Hamilton Depression Rating Scale scores and the Clinical Global Assessment Scale scores. Results: Young Mania Rating Scale scores were higher in manic episodes than in mixed episodes. There were no differences in gender frequency, CGI scores and rates of hospitalization, suicide attempts and psychotic symptoms, when mixed and manic episodes where compared. Patients with mixed episodes were younger Conclusion: In our sample, mixed states occurred at an earlier age than manic episodes. Contrary to previous reports, we did not find significant differences between manic and mixed episodes regarding severity of symptornatology, except for manic symptoms ratings, which were higher in acute manic patients. In part, this may be explained by the different criteria adopted on previous studies. C1 Univ Sao Paulo, Sch Med, Dept Psychiat, Inst Psychiat,Biopolar Disorder Res Program,PROMA, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Schwartzmann, AM (reprint author), Univ Sao Paulo, Hosp Clin, Fac Med, Inst Psiquiatria,PROMANProjeto Assitencia & Pesqu, Rua Ovidio Pires Campos,785, BR-05003010 Sao Paulo, Brazil. EM schwangela@terra.com.br RI Caetano, Sheila/H-5010-2012; OI Caetano, Sheila/0000-0001-8403-7078; Lafer, Beny/0000-0002-6132-9999; , Rodrigo/0000-0002-1315-7205 NR 25 TC 4 Z9 4 U1 0 U2 1 PU ASSOCIACAO BRASILEIRA DE PSIQUIATRIA PI SAO PAULO PA SUBSCRIPTION DEPARTMENT, RUA PEDRO DE TOLEDO, 967 - CASA 01, SAO PAULO, SP, BRAZIL SN 1516-4446 J9 REV BRAS PSIQUIATR JI Rev. Bras. Psiquiatr. PD JUN PY 2007 VL 29 IS 2 BP 130 EP 133 DI 10.1590/S1516-44462006005000036 PG 4 WC Psychiatry SC Psychiatry GA 182VE UT WOS:000247531300008 PM 17650532 ER PT J AU Saxena, R Voight, BF Lyssenko, V Burtt, NP de Bakker, PIW Chen, H Roix, JJ Kathiresan, S Hirschhorn, JN Daly, MJ Hughes, TE Groop, L Altshuler, D Almgren, P Florez, JC Meyer, J Ardlie, K Bostrom, KB Isomaa, B Lettre, G Lindblad, U Lyon, HN Melander, O Newton-Cheh, C Nilsson, P Orho-Melander, M Rastam, L Speliotes, EK Taskinen, MR Tuomi, T Guiducci, C Berglund, A Carlson, J Gianniny, L Hackett, R Hall, L Holmkvist, J Laurila, E Sjogren, M Sterner, M Surti, A Svensson, M Svensson, M Tewhey, R Blumenstiel, B Parkin, M DeFelice, M Barry, R Brodeur, W Camarata, J Chia, N Fava, M Gibbons, J Handsaker, B Healy, C Nguyen, K Gates, C Sougnez, C Gage, D Nizzari, M Gabriel, SB Chirn, GW Ma, QC Parikh, H Richardson, D Ricke, D Purcell, S AF Saxena, Richa Voight, Benjamin F. Lyssenko, Valeriya Burtt, Noel P. de Bakker, Paul I. W. Chen, Hong Roix, Jeffrey J. Kathiresan, Sekar Hirschhorn, Joel N. Daly, Mark J. Hughes, Thomas E. Groop, Leif Altshuler, David Almgren, Peter Florez, Jose C. Meyer, Joanne Ardlie, Kristin Bostroem, Kristina Bengtsson Isomaa, Bo Lettre, Guillaume Lindblad, Ulf Lyon, Helen N. Melander, Olle Newton-Cheh, Christopher Nilsson, Peter Orho-Melander, Marju Rastam, Lennart Speliotes, Elizabeth K. Taskinen, Marja-Riitta Tuomi, Tiinamaija Guiducci, Candace Berglund, Anna Carlson, Joyce Gianniny, Lauren Hackett, Rachel Hall, Liselotte Holmkvist, Johan Laurila, Esa Sjoegren, Marketa Sterner, Maria Surti, Aarti Svensson, Margareta Svensson, Malin Tewhey, Ryan Blumenstiel, Brendan Parkin, Melissa DeFelice, Matthew Barry, Rachel Brodeur, Wendy Camarata, Jody Chia, Nancy Fava, Mary Gibbons, John Handsaker, Bob Healy, Claire Nguyen, Kieu Gates, Casey Sougnez, Carrie Gage, Diane Nizzari, Marcia Gabriel, Stacey B. Chirn, Gung-Wei Ma, Qicheng Parikh, Hemang Richardson, Delwood Ricke, Darrell Purcell, Shaun CA Diabet Genetics Initiative Broad In Novartis Inst BioMedical Res TI Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels SO SCIENCE LA English DT Article ID RNA-BINDING PROTEIN; MACULAR DEGENERATION; RISK LOCI; OVEREXPRESSION; SUSCEPTIBILITY; GLUCOKINASE; POPULATION; VARIANTS; GENE; AGE AB New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases. C1 Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Diabet & Endocrinol Res Unit, Malmo, Sweden. Novartis Inst Biomed Res, Diabet & Metab Dis Area, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Univ Helsinki, Univ Helsinki Hosp, Dept Med, Helsinki, Finland. Skaraborg Inst, Skovde, Sweden. Malmska Municipal Hlth Ctr & Hosp, Pietarsaari, Finland. Folkhalsan Res Ctr, Helsinki, Finland. Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Community Med Res Unit, Malmo, Sweden. Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Med Res Unit, Malmo, Sweden. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Hughes, TE (reprint author), Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. EM thomase.hughes@novartis.com; leif.groop@med.lu.se; altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009; Voight, Benjamin/F-1775-2011; de Bakker, Paul/B-8730-2009; OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Ricke, Darrell/0000-0002-2842-2809; Tuomi, Tiinamaija/0000-0002-8306-6202 NR 30 TC 1786 Z9 1846 U1 14 U2 142 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 1 PY 2007 VL 316 IS 5829 BP 1331 EP 1336 DI 10.1126/science.1142358 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 173PS UT WOS:000246885600049 ER PT J AU Lopez-Meraz, ML Martinez, A Rocha, L AF Lopez-Meraz, Maria Leonor Martinez, Adrian Rocha, Luisa TI Effect of 8-OH-DPAT on electrographic activity during the kainic acid-induced status epilepticus in rats SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE 8-OH-DPAT; 5-HT1A receptor; kainic acid; status epilepticus; EEG activity; hippocampus; frontal cortex ID SUSTAINING STATUS EPILEPTICUS; RECEPTOR ACTIVATION; INDUCED SEIZURES; LIMBIC SEIZURES; 5-HT1A RECEPTOR; DENTATE GYRUS; CA1 NEURONS; SEROTONIN; HIPPOCAMPUS; STIMULATION AB The effect of 8-OH-DPAT, a 5-HT1A receptor agonist, on electrographic activity during the kainic acid (KA)-induced status epilepticus (SE) was evaluated in mate Wistar rats. Electrographic (EEG) recordings from the ventral hippocampus and the frontal cortex along with behavioral changes were evaluated in animals that received KA administration (10 mg/kg, i.p.) 20 min after saline solution (control group) or 8-OH-DPAT (1 mg/kg, s.c.) injection. Rats pretreated with 8-OH-DPAT presented augmented latency for wet dog shakes (71%), generalized seizures (54%) and behavioral SE (31%). 8-OH-DPAT delayed occurrence of the first KA-induced paroxystic spikes (70%), increased latency to the EEG SE (39%) and decreased spike frequency (35-43%) recorded from the frontal cortex, and increased the time necessary for the high voltage EEG activity synchronization of the hippocampus and the frontal cortex (125%). However, EEG ictal activity recorded in hippocampus was not modified after 8-OH-DPAT pretreatment. These results indicate that 8-OH-DPAT reduces the EEG activity associated with the KA-induced SE in the frontal cortex, but not the hippocampus, and suggest an inhibitory effect in the propagation of epileptic seizures during the KA-induced SE. (c) 2007 Published by Elsevier Ltd on behalf of British Epilepsy Association. C1 Ctr Invest & Estudios Avanzaods Sede Sur, Dept Farmacobiol, Mexico City, DF, Mexico. Inst Nacl Psiquiat Ramon de la Fuente Muniz, Direcc Invest Neurociencias, Mexico City, DF, Mexico. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Epilepsy Res Lab, Los Angeles, CA USA. RP Lopez-Meraz, ML (reprint author), VA Greater Los Angeles Healthcare Syst, Epilepsy Res Lab 151, 11301 Wilshire Blvd,Bldg 114,Room 139, Los Angeles, CA 90073 USA. EM lopezmerazml@ucla.edu NR 40 TC 7 Z9 7 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1059-1311 J9 SEIZURE-EUR J EPILEP JI Seizure PD JUN PY 2007 VL 16 IS 4 BP 365 EP 370 DI 10.1016/j.seizure.2007.02.009 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 167KE UT WOS:000246449800012 PM 17391992 ER PT J AU Signoretti, S Loda, M AF Signoretti, Sabina Loda, Massimo TI Prostate stem cells: From development to cancer SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE prostate; cancer; stem cells; cell lineage; development; p63; markers ID EPITHELIAL-CELLS; KERATIN EXPRESSION; BASAL-CELLS; PROSPECTIVE IDENTIFICATION; DIFFERENTIATION PATHWAYS; MYELOID-LEUKEMIA; PROXIMAL REGION; MOUSE PROSTATE; LUMINAL CELLS; RAT PROSTATE AB The cell of origin of prostate cancer is still unknown. The identification of these cells depends on understanding prostate cell differentiation lineage during development as well as adult prostate epithelium renewal. Recent advances in the field have shed light on the hierarchical relationship between epithelial prostate cells. On the basis of this knowledge, the isolation and characterization of prostate cancer stem cells may now be possible and could provide an explanation for the known clinical and molecular heterogeneity of human prostate cancer. (C) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Signoretti, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM ssignoretti@partners.org; massimo_loda@dfci.harvard.edu FU NCI NIH HHS [5P50CA90381, P01 CA089021]; NIDDK NIH HHS [5R21DK072152-02] NR 63 TC 25 Z9 27 U1 1 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD JUN PY 2007 VL 17 IS 3 BP 219 EP 224 DI 10.1016/j.semcancer.2006.04.004 PG 6 WC Oncology SC Oncology GA 173GA UT WOS:000246860300005 PM 16781871 ER PT J AU Ho, VT Linden, E Revta, C Richardson, PG AF Ho, Vincent T. Linden, Erica Revta, Carolyn Richardson, Paul G. TI Hepatic veno-occlusive disease after hematopoietic stern cell transplantation: Review and update on the use of defibrotide SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Review DE veno-occlusive disease (VOD); sinusoidal obstruction syndrome; defibrotide; stem cell transplantation; bone marrow transplantation ID BONE-MARROW-TRANSPLANTATION; TISSUE-PLASMINOGEN-ACTIVATOR; SINUSOIDAL OBSTRUCTION SYNDROME; MOLECULAR-WEIGHT HEPARIN; GEMTUZUMAB OZOGAMICIN EXPOSURE; REGIMEN-RELATED TOXICITY; HIGH-RISK POPULATION; ACUTE-RENAL-FAILURE; LOW-DOSE HEPARIN; RANDOMIZED-TRIAL AB Veno-occlusive disease (VOD) of the liver remains one of the most feared complications associated with high-dose chemotherapy and hematopoietic stem cell transplantation (SCT). As a clinical syndrome characterized by fluid retention, hyperbilirubinemia, and painful hepatomegaly, VOD incidence varies widely, but it is universally recognized that severe cases of VOD have an extremely poor prognosis, with mortality at day 100 after SCT in excess of 80%. Systemic anticoagulant and thrombolytic therapies have been tested extensively in this disease, but are largely ineffective and are associated with significant bleeding complications. In recent years, defibrotide (DF; a polydisperse oligonucleotide derived from porcine intestinal mucosa with antithrombotic and protective properties on the microvasculature but minimal hemorrhagic risk) has emerged as a promising therapy for VOD. In large, multicenter, international phase I/II trials targeting patients with severe VOD, DF has been associated with complete response rates between 36 and 60%, survival past transplant day 100 in the range of 32 to 50%, and few significant attributable side effects. On the basis of these encouraging results, a pivotal, prospective, multinational, phase III trial of DF is underway in patients with severe VOD, and should provide validation of this agent as a therapy for established disease with a high risk of mortality. This article reviews our current understanding of hepatic VOD after SCT and provides a summary of the data to date on the use of DF as both therapy and prophylaxis for this disease. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Ctr Hematol Oncol,Dept Adult Oncol, Boston, MA 02115 USA. RP Ho, VT (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Ctr Hematol Oncol,Dept Adult Oncol, 44 Binney St,D1B06, Boston, MA 02115 USA. EM vincent_ho@dfci.harvard.edu NR 153 TC 29 Z9 32 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD JUN PY 2007 VL 33 IS 4 BP 373 EP 388 DI 10.1055/s-2007-976173 PG 16 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 174TT UT WOS:000246966400011 PM 17525895 ER PT J AU Freytes, CO AF Freytes, Cesar O. TI Thromboembolic complications related to central venous access catheters in cancer patients SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE indwelling catheters; central venous catheterization; neoplasm; venous thrombosis; thrombolytic therapy ID DEEP-VEIN THROMBOSIS; FACTOR-V-LEIDEN; UPPER-EXTREMITY; DOUBLE-BLIND; RISK-FACTORS; INFECTIOUS COMPLICATIONS; PROSPECTIVE TRIAL; DEVICES; PROPHYLAXIS; PREVENTION AB Recent well-designed, prospective, controlled trials have demonstrated a lower incidence of catheter-related deep vein thrombosis (CRDVT) compared with earlier studies but this complication remains an important limitation to the delivery of drugs and supportive care to cancer patients. Prophylaxis of CRDVT with antithrombotic agents was not supported by recent prospective randomized trials, and its routine use is not recommended. Larger studies will be required to determine if cancer patients at particularly high risk for CRDVT can benefit from prophylaxis with antithrombotic agents. There are no prospective controlled studies to guide the therapy of CRDVT but treatment with anticoagulants remains the mainstay of therapy. Although recently published guidelines might help standardize the therapy of patients with CRDVT, prospective controlled studies are needed to determine the optimal therapy of this important complication of central venous catheters in cancer patients. C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. RP Freytes, CO (reprint author), Mail Code 7880,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM freytes@uthscsa.edu NR 74 TC 7 Z9 8 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD JUN PY 2007 VL 33 IS 4 BP 389 EP 396 DI 10.1055/s-2007-976174 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 174TT UT WOS:000246966400012 PM 17525896 ER PT J AU DenBoer, JW AF DenBoer, John W. TI Sexuality and fertility issues in ill health and disability: From early adolescence to adulthood SO SEXUALITY AND DISABILITY LA English DT Book Review DE sexuality; disabilities; fertility; adolescence; adulthood; health ID IMPACT C1 Harvard Univ, Sch Med, Boston Consortium Psychol Training Program, VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02130 USA. RP DenBoer, JW (reprint author), Harvard Univ, Sch Med, Boston Consortium Psychol Training Program, VA Boston Healthcare Syst, 116B,150 S Huntington Ave, Boston, MA 02130 USA. EM john.denboer@va.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD JUN PY 2007 VL 25 IS 2 BP 85 EP 87 DI 10.1007/s11195-007-9034-z PG 3 WC Rehabilitation SC Rehabilitation GA 182PS UT WOS:000247517100007 ER PT J AU McCarley, RW Chokroverty, S AF McCarley, Robert W. Chokroverty, Sudhansu TI Introduction to special issue of sleep medicine SO SLEEP MEDICINE LA English DT Editorial Material C1 Harvard Univ, Dept Psychiat, VA Boston Healthcare Syst, Brockton, MA 02301 USA. RP McCarley, RW (reprint author), Harvard Univ, Dept Psychiat, VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. EM robert_mccarley@hms.harvard.edu FU NHLBI NIH HHS [P50 HL060292, P50 HL060292-090002]; NIMH NIH HHS [R37 MH039683, R01 MH062522, R37 MH039683-23, R01 MH062522-05] NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD JUN PY 2007 VL 8 IS 4 BP 289 EP 290 DI 10.1016/j.sleep.2007.03.007 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 178OU UT WOS:000247230800001 PM 17470411 ER PT J AU Szymusiak, R Gvilia, I McGinty, D AF Szymusiak, Ronald Gvilia, Irma McGinty, Dennis TI Hypothalamic control of sleep SO SLEEP MEDICINE LA English DT Article DE hypothalamus ID VENTROLATERAL PREOPTIC NUCLEUS; EYE-MOVEMENT SLEEP; WAKING DISCHARGE PATTERNS; BASAL FOREBRAIN NEURONS; FOS PROTEIN EXPRESSION; LATERAL HYPOTHALAMUS; C-FOS; GALANINERGIC NEURONS; PROMOTING NEURONS; NERVOUS-SYSTEM AB A sleep-promoting function for the rostral hypothalamus was initially inferred from the presence of chronic insomnia following damage to this brain region. Subsequently, it was determined that a unique feature of the preoptic hypothalamus and adjacent basal forebrain is the presence of neurons that are activated during sleep compared to waking. Preoptic area "sleep-active" neurons have been identified by single and multiple-unit recordings and by the presence of the protein product of the c-Fos gene in the neurons of sleeping animals. Sleep-active neurons are located in several subregions of the preoptic area, occurring with high density in the ventrolateral preoptic area (vlPOA) and the median preoptic nucleus (MnPN). Neurons in the vlPOA contain the inhibitory neuromodulator, galanin, and the inhibitory neurotransmitter, GABA. A majority of MnPN neurons activated during sleep contain GABA. Anatomical tracer studies reveal projections from the vlPOA and MnPN to multiple arousal-regulatory systems in the posterior and lateral hypothalamus and the rostral brainstem. Cumulative evidence indicates that preoptic area neurons function to promote sleep onset and sleep maintenance by inhibitory modulation of multiple arousal systems. Recent studies suggest a role for preoptic area neurons in the homeostatic aspects of the regulation of both rapid eye movement (REM) and non-REM (NREM) sleep and as a potential target for endogenous somnongens, such as cytokines and adenosine. (c) 2007 Elsevier B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychol, Los Angeles, CA 90024 USA. I Beritashvili Inst Physiol, Thilisi, GA USA. RP Szymusiak, R (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, 16111 Plummer St, Sepulveda, CA 91343 USA. EM rszym@ucla.edu FU NHLBI NIH HHS [HL60296]; NIMH NIH HHS [MH63323] NR 72 TC 82 Z9 88 U1 4 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD JUN PY 2007 VL 8 IS 4 BP 291 EP 301 DI 10.1016/j.sleep.2007.03.013 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 178OU UT WOS:000247230800002 PM 17468047 ER PT J AU McCarley, RW AF McCarley, Robert W. TI Neurobiology of REM and NREM sleep SO SLEEP MEDICINE LA English DT Review DE REM; NREM ID PONTINE RETICULAR-FORMATION; FREELY MOVING CATS; EYE-MOVEMENT SLEEP; DORSAL RAPHE NUCLEUS; PEDUNCULOPONTINE TEGMENTAL NUCLEI; MESOPONTINE CHOLINERGIC NEURONS; ADENOSINE A(2A) RECEPTOR; VENTROLATERAL PREOPTIC NEURONS; SEROTONIN-CONTAINING NEURONS; RECIPROCAL INTERACTION-MODEL AB This paper presents an overview of the current knowledge of the neurophysiology and cellular pharmacology of sleep mechanisms. It is written from the perspective that recent years have seen a remarkable development of knowledge about sleep mechanisms, due to the capability of current cellular neurophysiological, pharmacological and molecular techniques to provide focused, detailed, and replicable studies that have enriched and informed the knowledge of sleep phenomenology and pathology derived from electroencephalographic (EEG) analysis. This chapter has a cellular and neurophysiological/neuropharmacologicaI focus, with an emphasis on rapid eye movement (REM) sleep mechanisms and non-REM (NREM) sleep phenomena attributable to adenosine. The survey of neuronal and neurotransmitter-related brainstem mechanisms of REM includes monoamines, acetylcholine, the reticular formation, a new emphasis on GABAergic mechanisms and a discussion of the role of orexin/hypcretin in diurnal consolidation of REM sleep. The focus of the NREM sleep discussion is on the basal forebrain and adenosine as a mediator of homeostatic control. Control is through basal forebrain extracellular adenosine accumulation during wakefulness and inhibition of wakefulness-active neurons. Over longer periods of sleep loss, there is a second mechanism of homeostatic control through transcriptional modification. Adenosine acting at the Al receptor produces an up-regulation of At receptors, which increases inhibition for a given level of adenosine, effectively increasing the gain of the sleep homeostat. This second mechanism likely occurs in widespread cortical areas as well as in the basal forebrain. Finally, the results of a new series of experimental paradigms in rodents to measure the neurocognitive effects of sleep loss and sleep interruption (modeling sleep apnea) provide animal model data congruent with those in humans. Published by Elsevier B.V. C1 VA Boston Healthcare Syst, Neurosci Lab, Brockton, MA 02301 USA. RP McCarley, RW (reprint author), VA Boston Healthcare Syst, Neurosci Lab, 940 Belmont St, Brockton, MA 02301 USA. EM robert_mccarley@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [R01 MH40,799, R37 MH39,683] NR 205 TC 230 Z9 240 U1 11 U2 63 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD JUN PY 2007 VL 8 IS 4 BP 302 EP 330 DI 10.1016/j.sleep.2007.03.005 PG 29 WC Clinical Neurology SC Neurosciences & Neurology GA 178OU UT WOS:000247230800003 PM 17468046 ER PT J AU Barrett, LF Bliss-Moreau, E Duncan, SL Rauch, SL Wright, CI AF Barrett, Lisa Feldman Bliss-Moreau, Eliza Duncan, Seth L. Rauch, Scott L. Wright, Christopher I. TI The amygdala and the experience of affect SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; HUMAN ORBITOFRONTAL CORTEX; FEARFUL FACES; ATTENTIONAL BIAS; EMOTIONAL INFORMATION; VISUAL AWARENESS; MACAQUE MONKEY; FUNCTIONAL MRI; INDIVIDUAL-DIFFERENCES AB The current study examined the hypothesis that amygdala activation serves as a neural precondition for negative affective experience. Participants' affective experience was measured by asking them to report on their momentary experiences several times a day over the course of a month using an electronic experience-sampling procedure. One year later, participants viewed backwardly masked depictions of fear while functional magnetic resonance imaging was used to measure their amygdala and fusiform gyrus activation. Negative affect, as measured during the experience-sampling procedure 1-year prior, was positively correlated with amygdala activation in response to these brief presentations of fear depictions. Furthermore, descriptive analyses indicated that fusiform gyrus activation and negative affective experience in the scanner were associated for participants reporting increased nervousness during the imaging procedure. The results are consistent with the interpretation that the amygdala contributes to negative affective experience by increasing perceptual sensitivity for negative stimuli. C1 [Barrett, Lisa Feldman; Bliss-Moreau, Eliza; Duncan, Seth L.] Boston Coll, Dept Psychol, Chestnut Hill, MA 02167 USA. [Barrett, Lisa Feldman; Rauch, Scott L.; Wright, Christopher I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Barrett, LF (reprint author), Boston Coll, Dept Psychol, 427 McGuinn Hall, Chestnut Hill, MA 02167 USA. EM barretli@bc.edu FU NIA NIH HHS [R01 AG030311, R01 AG030311-01, R01AG030311]; NIMH NIH HHS [K02 MH001981-05, K02 MH001981, K23 MH064806, K23MH64806] NR 90 TC 34 Z9 34 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD JUN PY 2007 VL 2 IS 2 BP 73 EP 83 DI 10.1093/scan/nsl042 PG 11 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 271UF UT WOS:000253813500002 PM 18392107 ER PT J AU Gutchess, AH Kensinger, EA Schacter, DL AF Gutchess, Angela H. Kensinger, Elizabeth A. Schacter, Daniel L. TI Aging, self-referencing, and medial prefrontal cortex SO SOCIAL NEUROSCIENCE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; AGE-RELATED DIFFERENCES; EVENT-RELATED FMRI; ALZHEIMERS-DISEASE; COGNITIVE CONTROL; DEFAULT-MODE; OLDER-ADULTS; CEREBRAL-CORTEX; BRAIN-FUNCTION; LIFE-SPAN AB The lateral prefrontal cortex undergoes both structural and functional changes with healthy aging. In contrast, there is little structural change in the medial prefrontal cortex, but relatively little is known about the functional changes to this region with age. Using an event-related fMRI design, we investigated the response of medial prefrontal cortex during self-referencing in order to compare age groups on a task that young and elderly perform similarly and that is known to actively engage the region in young adults. Nineteen young (M age = 23) and seventeen elderly (M age = 72) judged whether adjectives described themselves, another person, or were presented in upper case. We assessed the overlap in activations between young and elderly for the self-reference effect (self vs. other person), and found that both groups engage medial prefrontal cortex and mid-cingulate during self-referencing. The only cerebral differences between the groups in self versus other personality assessment were found in somatosensory and motor-related areas. In contrast, age-related modulations were found in the cerebral network recruited for emotional valence processing. Elderly (but not young) showed increased activity in the dorsal prefrontal cortex for positive relative to negative items, which could reflect an increase in controlled processing of positive information for elderly adults. C1 [Gutchess, Angela H.; Schacter, Daniel L.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Kensinger, Elizabeth A.] Boston Coll, Massachusetts Gen Hosp, Boston, MA USA. RP Gutchess, AH (reprint author), Harvard Univ, Dept Psychol, William James Hall 868,33 Kirkland St, Cambridge, MA 02138 USA. EM gutchess@nmr.mgh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061 FU NCRR NIH HHS [P41 RR14075]; NIA NIH HHS [AG008441, AG026920]; NIMH NIH HHS [MH 070199] NR 66 TC 92 Z9 94 U1 2 U2 17 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0919 J9 SOC NEUROSCI JI Soc. Neurosci. PD JUN PY 2007 VL 2 IS 2 BP 117 EP 133 DI 10.1080/17470910701399029 PG 17 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 249QZ UT WOS:000252245300004 PM 18633811 ER PT J AU Allen, JD Kennedy, M Wilson-Glover, A Gilligan, TD AF Allen, Jennifer D. Kennedy, Mark Wilson-Glover, Athene Gilligan, Timothy D. TI African-American men's perceptions about prostate cancer: Implications for designing educational interventions SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE prostate cancer screening; informed decision-making; African-American men; USA ID RANDOMIZED CONTROLLED-TRIAL; INFORMED DECISION-MAKING; HEALTH-CARE; CAUCASIAN MEN; ETHNIC-GROUPS; BLOOD-TEST; WHITE MEN; ANTIGEN; KNOWLEDGE; RACE AB This qualitative study explores African-American men's perceptions about prostate cancer (CaP) screening and assesses the acceptability of various strategies and settings for interventions to promote informed decision-making. We conducted four focus groups among healthy men (n = 37) and two groups among CaP survivors (n = 14) aged 35-70 in the greater Boston area, USA. Also, we conducted 14 in-depth interviews with key community informants. The audio-taped focus groups and interviews were transcribed, coded, and analyzed for emergent themes. Except for survivors, men had insufficient information about the prostate, the elevated cancer risk among African-Americans, and the controversy concerning screening. Key informants and focus group participants cited inadequate access to services, mistrust of the health system, poor relationships with medical providers, and perceived threats to male sexuality as major barriers to receiving prostate care. They recommended that interventions be embedded in community settings, address men's overall health, and be administered by culturally competent providers, and repeatedly emphasized trust building and a sustained presence in the community. Efforts to present balanced information about Cal? screening may be hindered by lingering mistrust of the medical system, poor relationships between patients and providers, and enthusiastic support for screening on the part of CaP survivors. Implications for interventions are discussed. (c) 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Publ Hlth Soc Human Dev & Hlth, Boston, MA 02115 USA. Boston Coll, William Connell Sch Nursing, Chestnut Hill, MA 02167 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Allen, JD (reprint author), Harvard Univ, Sch Publ Hlth Soc Human Dev & Hlth, 44 Binney St, Boston, MA 02115 USA. EM jennifer_allen@dfci.harvard.edu; mark_kennedy@dfci.harvard.edu; athene_wilson-glover@dfci.harvard.edu; gilligt@ccf.org RI Allen, Jennifer/M-2113-2015; OI Gilligan, Timothy/0000-0003-2308-9303 NR 71 TC 59 Z9 59 U1 4 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JUN PY 2007 VL 64 IS 11 BP 2189 EP 2200 DI 10.1016/j.socscimed.2007.01.007 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 176CF UT WOS:000247059700002 PM 17399877 ER PT J AU Peteet, J AF Peteet, John TI Spirituality and mental health SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Peteet, J (reprint author), Dana Farber Canc Inst, 44 Binney St,Gossman 411, Boston, MA 02115 USA. EM John_Peteet@dfci.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD JUN PY 2007 VL 100 IS 6 BP 620 EP 620 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 177PZ UT WOS:000247166300023 PM 17591324 ER PT J AU Miovic, M AF Miovic, Michael TI Spirituality, OCD, and life-threatening illness SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; THERAPY; PREDICTORS C1 Dana Farber Canc Inst, Psychosocial Oncol Program, Boston, MA 02115 USA. RP Miovic, M (reprint author), Dana Farber Canc Inst, Psychosocial Oncol Program, 44 Binney St,G420, Boston, MA 02115 USA. EM mmiovic@partners.org NR 13 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD JUN PY 2007 VL 100 IS 6 BP 649 EP 651 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 177PZ UT WOS:000247166300031 PM 17591332 ER PT J AU Sauerwein, W Matsumura, A Moss, R Busse, P Wittig, A AF Sauerwein, W. Matsumura, A. Moss, R. Busse, P. Wittig, A. TI Boron neutron capture therapy (BNCT) - radiotherapy of the future? SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Meeting Abstract CT 13th Congress of the Deutschen-Gesellschaft-fur-Radioonkologie CY JUN 07-10, 2007 CL Hannover, GERMANY SP Deutsch Gesell Radioonkol C1 Univ Klinikum Essen, Essen, Germany. Univ Tokushima, Tokushima 770, Japan. European Commiss Joint Res Ctr, Inst Energy, Petten, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD JUN PY 2007 VL 183 SU 1 BP 43 EP 43 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 176GC UT WOS:000247071800114 ER PT J AU Schwarte, S Bremer, M Roemermann, D Ballmaier, M Hoffmann, M AF Schwarte, S. Bremer, M. Roemermann, D. Ballmaier, M. Hoffmann, M. TI Immunoregulatory CD8 T-cell-mediated prevention of Graft-versus-Host-Disease after using low-dose rates of total body irradiation in experimental models SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Meeting Abstract CT 13th Congress of the Deutschen-Gesellschaft-fur-Radioonkologie CY JUN 07-10, 2007 CL Hannover, GERMANY SP Deutsch Gesell Radioonkol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany. Hannover Med Sch, Dept Vis Sci, Dept Visceral & Transplantat Surg, D-3000 Hannover, Germany. Hannover Med Sch, Cell Sorting Core Facil, D-3000 Hannover, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD JUN PY 2007 VL 183 SU 1 BP 133 EP 133 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 176GC UT WOS:000247071800377 ER PT J AU Sauerwein, W Blondin, A Cuttone, G Chauvel, P Busse, P AF Sauerwein, W. Blondin, A. Cuttone, G. Chauvel, P. Busse, P. TI Protons in radiation therapy SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Meeting Abstract CT 13th Congress of the Deutschen-Gesellschaft-fur-Radioonkologie CY JUN 07-10, 2007 CL Hannover, GERMANY SP Deutsch Gesell Radioonkol C1 Univ Hosp Essen, Essen, Germany. Ion Beam Applicat SA, Louvain, Belgium. INFN, Catania, Italy. Ctr Antoine Lacassagne, F-06054 Nice, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI cuttone, giacomo/C-4085-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD JUN PY 2007 VL 183 SU 1 BP 153 EP 153 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 176GC UT WOS:000247071800438 ER PT J AU Jouvent, E Viswanathan, A Mangin, JF O'Sullivan, M Guichard, JP Gschwendtner, A Cumurciuc, R Buffon, F Peters, N Pachai, C Bousser, MG Dichgans, M Chabriat, H AF Jouvent, Eric Viswanathan, Anand Mangin, Jean-Francois O'Sullivan, Mike Guichard, Jean-Pierre Gschwendtner, Andreas Cumurciuc, Rodica Buffon, Frederique Peters, Nils Pachai, Chahin Bousser, Marie-Germaine Dichgans, Martin Chabriat, Hugues TI Brain atrophy is related to lacunar lesions and tissue microstructural changes in CADASIL SO STROKE LA English DT Article DE CADASIL; cerebral atrophy; cerebral microhemorrhage; diffusion; lacune; white matter hyperintensities ID AUTOSOMAL-DOMINANT ARTERIOPATHY; ISCHEMIC VASCULAR-DISEASE; WHITE-MATTER; SUBCORTICAL INFARCTS; COGNITIVE DECLINE; STROKE; MRI; VOLUME; PROGRESSION; DEMENTIA AB Background and Purpose - Cerebral atrophy has been recently recognized as a key marker of disease progression in cerebral autosomal- dominant arteriopathy with subcortical infarcts and leukoencephalopathy ( CADASIL). The contribution of subcortical cerebral lesions in this process remains undetermined. The aim of this study was to investigate the relationships between cerebral volume and different types of subcortical MRI lesions in CADASIL. Methods - Demographic, clinical, and laboratory data from 147 patients with CADASIL recruited from a prospective cohort study were analyzed. Validated methods were used to determine the ratio of brain volume to intracranial cavity volume ( brain parenchymal fraction [ BPF]), volume of white matter hyperintensities, volume of lacunar lesions, number of cerebral microhemorrhages, and mean apparent diffusion coefficient. Associations between BPF, clinical scales, and the different subcortical MRI markers were tested. Results - BPF obtained in 129 patients was significantly associated with the Mattis dementia rating scale ( P < 0.0001), Mini- Mental State Examination ( P = 0.002), and modified Rankin scale ( P < 0.0001) after adjustment for age and sex. Multiple linear regression modeling showed that BPF was independently associated with mean apparent diffusion coefficient ( P < 0.0001), volume of lacunar lesions ( P < 0.004), and age ( P < 0.0001), accounting for 46% of the observed variance in BPF but not with volume of white matter hyperintensities or number of microhemorrhages. Conclusions - In association with age, mean apparent diffusion coefficient and volume of lacunar lesions are strong and independent MRI predictors of BPF, a key marker of cognitive and motor disability in CADASIL. These results suggest brain atrophy is related to remote and/ or diffuse consequences of both lacunar lesions and widespread microstructural alterations within the brain outside lacunar lesions. C1 CHU Lariboisiere, Dept Neurol, APHP, Paris, France. Univ Paris 07, Paris, France. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CEA, Serv Hosp Frederic Joliot, Unite NeuroAnat Fonct, F-91406 Orsay, France. Univ Munich, Klinikum Grosshadern, Dept Neurol, D-8000 Munich, Germany. CHU Lariboisiere, APHP, Dept Neuroradiol, Paris, France. RP Chabriat, H (reprint author), Hop Lariboisiere, Serv Neurol, 2 Rue Ambroise Pare, F-75010 Paris, France. EM hugues.chabriat@lrb.ap-hop-paris.fr RI turton, miranda/F-4682-2011; O'Sullivan, Michael/A-1796-2010; Jouvent, Eric/B-4320-2014; Chabriat, Hugues/G-5699-2010 OI Jouvent, Eric/0000-0001-7797-2236; Chabriat, Hugues/0000-0001-8436-6074 NR 24 TC 57 Z9 59 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2007 VL 38 IS 6 BP 1786 EP 1790 DI 10.1161/STROKEAHA.106.478263 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 172TK UT WOS:000246827100020 PM 17446424 ER PT J AU Wong, DR Torchiana, DF Vander Salm, TJ Agnihotri, AK Bohmer, RMJ Ali, IS AF Wong, Daniel R. Torchiana, David F. Vander Salm, Thomas J. Agnihotri, Arvind K. Bohmer, Richard M. J. Ali, Imtiaz S. TI Impact of cardiac intraoperative precursor events on adverse outcomes SO SURGERY LA English DT Article ID BYPASS GRAFT-SURGERY; QUALITY INDICATORS; HEALTH-CARE; MORTALITY; MODELS AB Background. Although extensive study has been directed (it the influence of patient factors and comorbidities on cardiac surgical outcomes, less attention has been focused on process. We sought to examine the relationship between intraoperative precursor events (those events that precede and are requisite for the occurrence of an adverse event) and adverse outcomes themselves. Methods. Anonymous, prospectively collected intraoperative data was merged with database outcomes for 450 patients undergoing major adult cardiac operations. Precursor events were categorized by type, person most affected, severity, and compensation. Number and categories of precursor events were analyzed as predictors of a composite outcome combining death or near miss complications (DNM), using logistic regression. Results. Precursor events occurred more frequently in cases with a DNM outcome than in those with no adverse event (2.7 +/- 2.4 vs 2.0 +/- 2.3/procedure, P = .005). After adjustment for other patient characteristics, the number of precursor events remained an independent predictor of DNM (RR, 1.14 per event [1.04 to 1.24]). Of 990 events, 35.6% related to management, 28.8% were technical, and 22.8% were environment-related. The surgeon was most affected in 40.8%, and 16.5% were of major severity. Men categories of precursor events were analyzed, major severity events and those most affecting the surgeon were independent predictors of DNM. Conclusions. More detailed study of process in complex operations may lead to improved quality of care and patient safety. Special attention must be paid particularly to high risk patients and high risk precursor events. C1 Maritime Heart Ctr, Halifax, NS, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. N Shore Med Ctr, Salem, MA USA. Harvard Univ, Sch Business, Boston, MA 02115 USA. RP Ali, IS (reprint author), Queen Elizabeth II Hlth Sci Ctr, Div Cardiac Surg, 1796 Summer St,Suite 2269, Halifax, NS B3H 3A7, Canada. EM imtiaz.ali@dal.ca NR 26 TC 8 Z9 8 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 2007 VL 141 IS 6 BP 715 EP 722 DI 10.1016/j.surg.2007.01.017 PG 8 WC Surgery SC Surgery GA 179NF UT WOS:000247295900004 PM 17560247 ER PT J AU Lin, T Chen, HZ Koustova, E Sailhamer, EA Li, YQ Shults, C Liu, BL Rhee, P Kirkpatrick, J Alam, HB AF Lin, Tom Chen, Huazhen Koustova, Elena Sailhamer, Elizabeth A. Li, Yongqing Shults, Christian Liu, Baoling Rhee, Peter Kirkpatrick, John Alam, Hasan B. TI Histone deacetylase as therapeutic target in a rodent model of hemorrhagic shock: Effect of different resuscitation strategies on lung and liver SO SURGERY LA English DT Article; Proceedings Paper CT 1st Annual Academic Surgical Congress of the Association-for-Academic-Surgery CY FEB 07-11, 2006 CL San Diego, CA SP Assoc Acad Surg ID NF-KAPPA-B; GENE-EXPRESSION; FLUID RESUSCITATION; CARDIAC HISTONES; ACETYLATION; INHIBITORS; ACTIVATION; FAMILY AB Background. DNA transcription is regulated in part by acetylation of nuclear histones, controlled by 2 groups of enzymes: histone deacetylases (HDAC) and histone acetyl transferases (HAT). We have shown previously that hemorrhage and resuscitation are associated with HDAC/HAT imbalance, which influences the acetylation status of cardiac histones. The goals of this study were to determine whether (1) resuscitation after hemorrhage affects histone acetylation in a fluid- and organ-specific fashion; and (2) administration of HDAC inhibitors influences histone acetylation and subsequent gene expression. Methods. In the first experiment, rats (n = 6/group) were subjected to volume-controlled hemorrhage and resuscitated with: (1) racemic lactated Ringer's (DL-LR); (2) L-lactated Ringer's (L-LR); (3) 7.5% hypertonic saline (HTS); (4) ketone Ringer's (KR); or (5) pyruvate Ringer's (PR). Control groups included: (6) no hemorrhage (Sham); and (7) hemorrhage with no resuscitation (NR). In the second experiment (n = 5/group), 3 HDAC inhibitors, valproic acid (VPA), trichostatin A (TSA), and suberoylanilide hydroxamic acid (SAHA), were added to normal saline and used as fluid for resuscitation. At the end of resuscitation, lung and liver tissues were subjected to subcellular protein fractionation and Western blotting to analyze histone acetylation. In addition, cDNA microarrays and RT-PCR were used to measure expression of selected genes. Results. Hemorrhage did not change the level of histone acetylation in lungs, whereas resuscitation predominantly hyperacelylated histones. An analysis of histone acetylation on 10 lysine sites showed that L-LR HTS, and KR resuscitation caused the largest number of changes (7, 6, and 6 respectively). SAHA hyperacetylated 7 sites in liver and affected expression of 57 genes (44 up, 13 down). Conclusions. Resuscitation with various fluids, as well as infusion of pharmacologic HDA C inhibitors affects histone acelylation in a fluid- and organ-specific fashion, even when administered post-insult for a limited period of time. Uniquely affected genes are associated with metabolism, cellular growth, proliferation, differentiation, transformation, and cellular signaling. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Washington Hosp Ctr, Dept Surg, Washington, DC 20010 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Alam, HB (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org NR 28 TC 36 Z9 41 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 2007 VL 141 IS 6 BP 784 EP 794 DI 10.1016/j.surg.2007.01.014 PG 11 WC Surgery SC Surgery GA 179NF UT WOS:000247295900012 PM 17560255 ER PT J AU Stylopoulos, N Vosburgh, KG AF Stylopoulos, Nicholas Vosburgh, Kirby G. TI Assessing technical skill in surgery and endoscopy: A set of metrics and an algorithm (C-PASS) to asses skills in surgical and endoscopic procedures SO SURGICAL INNOVATION LA English DT Article DE surgical performance; laparoscopy; endoscopy; performance characterization ID MINIMALLY INVASIVE SURGERY; LAPAROSCOPIC ULTRASONOGRAPHY; OPERATING-ROOM; SYSTEM; VIDEO AB Historically, the performance of surgeons has been assessed subjectively by senior surgical staff in both training and operating environments. In this work, the position and motion of surgical instruments are analyzed through an objective process, denoted C-PASS, to measure surgeon performance of laparoscopic, endoscopic, and image-guided procedures. To develop C-PASS, clinically relevant performance characteristics were identified. Then measurement techniques for parameters that represented each characteristic were derived, and analytic techniques were implemented to transform these parameters into explicit, robust metrics. The metrics comprise the C-PASS performance assessment methods which has been validated over the last 3 years in studies of laparoscopy and endoscopy. These studies show that C-PASS is straightforward, reproducible, and accurate. It is sufficiently powerful to assess the efficiency of these complex processes. It is likely that C-PASS and similar approaches will improve skills acquisition and learning and also enable the objective comparison of systems and techniques. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Ctr Integrat Med & Innovat Technol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, CIMIT Image Guidance Lab, Boston, MA 02114 USA. RP Vosburgh, KG (reprint author), 165 Cambridge St,Suite 702, Boston, MA 02114 USA. EM kirby@bwh.harvard.edu NR 36 TC 17 Z9 17 U1 0 U2 2 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1553-3506 J9 SURG INNOV JI Surg. Innov. PD JUN PY 2007 VL 14 IS 2 BP 113 EP 121 DI 10.1177/1553350607302330 PG 9 WC Surgery SC Surgery GA 178OR UT WOS:000247230500007 PM 17558017 ER PT J AU Li, SM Topchy, I Kocsis, B AF Li, Shaomin Topchy, Irina Kocsis, Bernat TI The effect of atropine administered in the medial septum or hippocampus on high- and low-frequency theta rhythms in the hippocampus of urethane anesthetized rats SO SYNAPSE LA English DT Article DE electroencephalogram; neuronal oscillations; cholinergic mechanisms ID BRAIN-STEM; SUPRAMAMMILLARY NUCLEUS; SEPTOHIPPOCAMPAL PATHWAY; GABAERGIC NEURONS; SLOW ACTIVITY; MODULATION; OSCILLATIONS; MEMORY; EEG; CA1 AB Cholinergic mechanisms are critical for the generation of hippocampal theta rhythm. Cholinergic innervation of the hippocampus originates from the medial septum (MS) and cholinergic receptors are expressed in both the MS and hippocampus. In this study, we compared the effects of the muscarinic receptor antagonist atropine in the MS and the hippocampus on theta generation. Hippocampal theta rhythm was elicited by electrical stimulation of the pontine reticular formation using series of stimuli with varying intensities. Atropine was administered either systemically (50 mg/kg i.p.) or locally in the MS (microdialysis; 25 and 75 mM for 30 or 90 min) or in the hippocampus on one side (microinjection; 20 or 40 ug). The relative power at the peak theta frequency was calculated and averaged over episodes of low-intensity and high-intensity stimulations. We found that atropine drastically reduced theta rhythmic synchronization when injected in either location. After MS administration of atropine, however, high-frequency theta elicited by high-intensity stimuli was more resistant (58% and 67% decrease after 25 mM and 75 mM atropine, respectively) than slow theta elicited by low-intensity stimuli (86% and 91% decrease). There was no significant difference between the powers of the two oscillations after hippocampal injections (70-75% decrease). We conclude that the theta suppressing effect of atropine involves both hippocampal and septal mechanisms and that low-frequency theta as compared with fast theta rhythm is more sensitive to muscarinic acetylcholine receptor antagonism in the MS but not in the hippocampus. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat,BIDMC,Lab Neurophysiol, Boston, MA 02115 USA. RP Kocsis, B (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Psychiat,BIDMC,Lab Neurophysiol, 330 Brookline Ave,BT-551, Boston, MA 02115 USA. EM bernat_kocsis@hms.harvard.edu RI Kocsis, Bernat/A-8377-2008 FU PHS HHS [62525] NR 54 TC 17 Z9 17 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUN PY 2007 VL 61 IS 6 BP 412 EP 419 DI 10.1002/syn.20388 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 154VB UT WOS:000245534800006 PM 17372965 ER PT J AU Adrover, E Berger, MA Perez, AA Tarazi, FI Antonelli, MC AF Adrover, Ezequiela Berger, Maria Alejandra Perez, Adriana A. Tarazi, Frank I. Antonelli, Marta C. TI Effects of prenatal stress on dopamine D2 receptor asymmetry in rat brain SO SYNAPSE LA English DT Article ID NUCLEUS-ACCUMBENS; FEMALE RATS; BEHAVIOR; LATERALIZATION; METABOLISM; SYSTEMS; CORTEX C1 Univ Buenos Aires, Fac Farm & Bioquim, Inst Quim & Fisioquim Biol, CONICET, Buenos Aires, DF, Argentina. Univ Buenos Aires, Fac Ciencias Exactas & Nat, Lab Biometria, Buenos Aires, DF, Argentina. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Belmont, MA USA. RP Antonelli, MC (reprint author), IQUIFIB, Fac Farm & Bioquim, Junin 956, RA-1113 Buenos Aires, DF, Argentina. EM mca@ffyb.uba.ar NR 23 TC 10 Z9 10 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUN PY 2007 VL 61 IS 6 BP 459 EP 462 DI 10.1002/syn.20389 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 154VB UT WOS:000245534800011 PM 17372983 ER PT J AU Spagnoletti, CL Rubio, DM McNeil, MA AF Spagnoletti, Carla L. Rubio, Doris M. McNeil, Melissa A. TI Internal medicine residents' preparedness to care for reproductive-age and pregnant women SO TEACHING AND LEARNING IN MEDICINE LA English DT Article ID HEALTH CURRICULUM; INFERTILITY; COMPETENCES; ATTITUDES; SKILLS; NEED AB Background. Research that addresses whether residents are prepared to deliver preconception care and manage medical conditions in pregnant and postpartum women has beet? scarce since the publication of women's health competency guidelines for internists in 1997. Purpose: To investigate current attitudes, training, and perceived preparedness in these areas and to explore relationships between resident characteristics and preparedness. Methods: A 62-item questionnaire was given to 105 internal medicine residents and recent graduates at two affiliated residency programs. Results: Eighty-five surveys were returned. Most respondents reported that they had minimal training and were unprepared in these areas but felt that learning these topics is important. Perceived preparedness correlated strongly with relevant didactic and clinical training but was not associated with gender, residency track, or career plan. Conclusions: In light of published competency guidelines, internal medicine training programs should consider adding or increasing curricular content to improve residents' perceived preparedness to deliver care to reproductive-age and pregnant women. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. RP Spagnoletti, CL (reprint author), 9W 923 Montefiore Hosp,200 Lothrup St, Pittsburgh, PA 15213 USA. EM spangloletticl@upmc.edu NR 23 TC 6 Z9 6 U1 1 U2 1 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1040-1334 J9 TEACH LEARN MED JI Teach. Learn. Med. PD SUM PY 2007 VL 19 IS 3 BP 257 EP 263 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 187LV UT WOS:000247850100008 PM 17594221 ER PT J AU Sharma, V Cui, HY Whalen, G Khan, A Torres, M AF Sharma, Vibhavasu Cui, Hongyi Whalen, Giles Khan, Ashraf Torres, Mira TI A case of trabecular adenoma of the thyroid with black pigmentation SO THYROID LA English DT Article ID MINOCYCLINE; CARCINOMA C1 Univ Massachusetts, Med Ctr, Dept Endocrinol, Worcester, MA USA. Univ Massachusetts, Med Ctr, Dept Surg, Worcester, MA USA. Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA USA. RP Sharma, V (reprint author), Southview Hosp, Joslin Diabet Ctr, 1989 Miamisburg Centerville Rd, Dayton, OH 45459 USA. EM vibhavasu.sharma@kmcnetwork.org NR 7 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUN PY 2007 VL 17 IS 6 BP 593 EP 594 DI 10.1089/thy.2006.0151 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 186SW UT WOS:000247799500018 PM 17614784 ER PT J AU Levin, M AF Levin, Michael TI Large-scale biophysics: ion flows and regeneration SO TRENDS IN CELL BIOLOGY LA English DT Review ID PARTIAL LIMB REGENERATION; ELECTRICAL-STIMULATION; GAP-JUNCTIONS; CHICK-EMBRYO; SUSTAINED DEPOLARIZATION; TRANSCRIPTION FACTOR; HUMAN KERATINOCYTES; NEURONAL APOPTOSIS; TAIL REGENERATION; NERVOUS-SYSTEM AB Regeneration requires exquisite orchestration of growth and morphogenesis. A powerful but still largely mysterious system of biophysical signals functions during regeneration, embryonic development and neoplasm. Ion transporters generate pH and voltage gradients, as well as ion fluxes, regulating proliferation, differentiation and migration. Endogenous bioelectrical signals are implicated in the control of wound healing, limb development, left-right patterning and spinal cord regeneration. Recent advances in molecular biology and imaging technology have allowed unprecedented insight into the sources and downstream consequences of ion flows. In complement to the current focus on molecular genetics and stem cell biology, artificial modulation of bioelectrical signals in somatic tissues is a powerful modality that might result in profound advances in understanding and augmentation of regenerative capacity. C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Ctr Regenerat & Dev Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Ctr Regenerat & Dev Biol, 188 Longwood Ave, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCRR NIH HHS [C06RR11244] NR 89 TC 93 Z9 98 U1 1 U2 16 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JUN PY 2007 VL 17 IS 6 BP 261 EP 270 DI 10.1016/j.tcb.2007.04.007 PG 10 WC Cell Biology SC Cell Biology GA 182MH UT WOS:000247508200002 PM 17498955 ER PT J AU Duda, DG Batchelor, TT Willett, CG Jain, RK AF Duda, Dan G. Batchelor, Tracy T. Willett, Christopher G. Jain, Rakesh K. TI VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; RENAL-CELL CARCINOMA; TYROSINE KINASE INHIBITOR; ANTIANGIOGENIC THERAPY; PHASE-I; VASCULAR NORMALIZATION; TUMOR VASCULATURE; BREAST-CANCER; FACTOR RECEPTOR-1 AB Despite setbacks, the clinical development of antiangiogenic agents has accelerated remarkably over the past 3-4 years. Consequently, there are currently three direct inhibitors of the VEGF pathway approved for use in cancer therapy. Other agents that block the VEGF pathway are in advanced stages of clinical development and have shown promising results. With these exciting developments come crucial questions regarding the use of these new molecular-targeted agents, alone or in combination with standard cytotoxic or targeted agents. Importantly, the mechanisms of action of anti-VEGF therapy remain unknown. Here, we discuss several potential mechanisms of action such as tumor vascular normalization, bone marrow-derived cell recruitment blockade and cytostatic effects of anti-VEGF therapy. We review the current progress, the major stumbling blocks and the future directions for anti-cancer therapy using anti-VEGF agents, emphasizing clarification of the underlying molecular mechanisms of action and biomarker identification and validation. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, 100 Blossom St,Cox-734, Boston, MA 02114 USA. EM jain@steele.ntgh.harvard.edu FU NCI NIH HHS [P01 CA080124, P01-CA80124, R01 CA115767, P01 CA080124-08, R01 CA115767-03, R01-CA115767, R21 CA099237, R21 CA099237-02, R21 CA117079, R21 CA117079-02, R21-CA099237, R21-CA117079] NR 69 TC 79 Z9 84 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD JUN PY 2007 VL 13 IS 6 BP 223 EP 230 DI 10.1016/j.molmed.2007.04.001 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 184PS UT WOS:000247654700002 PM 17462954 ER PT J AU Zhang, JQ Loughlin, KR Zou, KH Haker, S Tempany, CMC AF Zhang, Jian Qing Loughlin, Kevin R. Zou, Kelly H. Haker, Steven Tempany, Clare M. C. TI Role of endorectal coil magnetic resonance imaging in treatment of patients with prostate cancer and in determining radical prostatectomy surgical margin status: Report of a single surgeon's practice SO UROLOGY LA English DT Article ID CARCINOMA; MEN AB Objectives To evaluate the role of the combination of endorectal coil and external multicoil array magnetic resonance imaging (MRI) in the management of prostate cancer and predicting the surgical margin status in a single-surgeon practice. Methods We reviewed all patients referred by a single Surgeon from January 1993 to May 2002 for staging prostate MRI before selecting treatment. All MRI examinations were performed using 1.5T (Signa, GE Medical Systems) with a combination of endorectal and pelvic multicoil array. The tumor size, stage, and total gland volume on MRI, prostate-specific antigen (PSA) level, and Gleason score were all compared with the pathologic stage and diagnosis of positive surgical margins (PSMs). Results A total of 232 patients were evaluated, of whom 110 underwent radical prostatectomy, all performed by one surgeon (group 1), and 122 did not (group 2). The results showed that MRI stage, PSA level, and age were all significantly different (P <0.001). In group 1, the results showed a high specificity (99%) and accuracy (91%) for MRI staging of T3 cancer. The postoperative follow-up (median 4.5 years) revealed that 90% of men had PSA levels of less than '0.1 ng/mL. The PSM rate was 16%. No significant difference was found on MRI between the PSM group and non-PSM group. A single tumor length greater than 1.8 cm was the cutpoint above which PSMs were found (P = 0.002). Conclusions The results of our study have shown that the corribined use of clinical data and endorectal MRI can help optimize patient treatment and selection for surgery and, in a single surgeon's practice, lead to successful outcomes. C1 Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Tempany, CMC (reprint author), Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, LI 050,75 Francis St, Boston, MA 02115 USA. EM ctempany@bwh.harvard.edu FU NCI NIH HHS [P01 CA067165, R01 CA109246, R01 CA111288, R01 CA111288-01A1, R01 CA109246-02, P01 CA067165-09A20007]; NCRR NIH HHS [U41 RR019703-01A29002, U41 RR019703-037966, U41 RR019703, U41 RR 019703]; NIA NIH HHS [R01 AG019513, R01 AG 19513, R01 AG019513-01] NR 10 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUN PY 2007 VL 69 IS 6 BP 1134 EP 1137 DI 10.1016/j.urology.2007.01.094 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 188KC UT WOS:000247917800026 PM 17572201 ER PT J AU Mavropoulos, JC Partin, AW Amling, CL Terris, MK Kane, CJ Aronson, WJ Presti, JC Mangold, LA Freedland, SJ AF Mavropoulos, John C. Partin, Alan W. Amling, Christopher L. Terris, Martha K. Kane, Christopher J. Aronson, William J. Presti, Joseph C., Jr. Mangold, Leslie A. Freedland, Stephen J. TI Do racial differences in prostate size explain higher serum prostate-specific antigen concentrations among black men? SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; ANDROGEN RECEPTOR; WHITE PATIENTS; TUMOR VOLUME; CANCER; HYPERPLASIA; PROGRESSION; SPECIMENS; PREDICTOR; AGE AB Objectives To determine whether elevated serum prostate-specific antigen (PSA) values in black men are due, at least partially, to larger prostate size among black men. Methods The study population consisted of two cohorts: (1) 1410 men undergoing radical prostatectomy between 1988 and 2005 at five equal-access medical centers comprising the Shared Equal Access Regional Cancer Hospital (SEARCH) Database; and (2) 9601 men undergoing radical prostatectomy between 1988 and 2004 at the Johns Hopkins Hospital. We evaluated the association between race and serum PSA value and prostate weight using multivariable linear regression while adjusting for demographic and clinicopathologic cancer characteristics. Results In both cohorts, black men had higher serum PSA values (P <= 0.001). After adjusting for either demographic characteristics or demographic and cancer-specific characteristics, there were no significant associations between race and prostate size in either cohort. After adjusting for multiple demographic, clinical, and pathologic cancer-specific characteristics, black men had 15% higher serum PSA values relative to white men in both the SEARCH (P = 0.001) and Hopkins cohorts (P <0.001). Conclusions In this study of patients undergoing radical prostatectomy in two very different practice settings, black men in both cohorts had higher serum PSA values relative to white men, despite adjustment for demographic and cancer-specific characteristics, including prostate weight. The lack of significant association between race and prostate size suggests that alternative reasons are needed to explain higher serum PSA values in black men. C1 Duke Univ, Med Ctr, Div Urol Surg, Duke Prostate Ctr,Sch Med, Durham, NC 27710 USA. Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Sch Med, Duke Prostate Ctr, Dept Surg, Durham, NC 27710 USA. Vet Adm Med Ctr, Urol Sect, Dept Surg, Durham, NC USA. Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA. Univ Alabama, Dept Urol, Birmingham, AL USA. Med Coll Georgia, Dept Surg, Vet Adm Med Ctr, Urol Sect, Augusta, GA 30912 USA. USN, San Diego Hosp, Dept Urol, San Diego, CA 92152 USA. Vet Adm Med Ctr, Urol Sect, Dept Surg, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. Vet Adm Greater Los Angeles Healthcare Syst, Urol Sect, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. Vet Adm Med Ctr, Urol Sect, Dept Surg, Palo Alto, CA 94304 USA. RP Freedland, SJ (reprint author), Duke Univ, Med Ctr, Div Urol Surg, Duke Prostate Ctr,Sch Med, Box 2626, Durham, NC 27710 USA. EM steve.freedland@duke.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [R01CA100938, P50CA58236, P50 CA92131-01A1, P50 CA092131-01A1, P50 CA092131, R01 CA100938, R01 CA100938-05, P50 CA058236] NR 20 TC 11 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUN PY 2007 VL 69 IS 6 BP 1138 EP 1142 DI 10.1016/j.urology.2007.01.102 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 188KC UT WOS:000247917800027 PM 17572202 ER PT J AU Aryana, A Williams, MA AF Aryana, Arash Williams, Mark A. TI Marijuana as a trigger of cardiovascular events: Speculation or scientific certainty? SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Review DE marijuana; cardiovascular disease; tachyarrhythmias; myocardial infarction; vascular disease; congenital heart disease ID PLACEBO-MARIHUANA SMOKING; MYOCARDIAL-INFARCTION; CANNABIS ARTERITIS; ANGINA-PECTORIS; STROKE; DELTA-9-TETRAHYDROCANNABINOL; ASSOCIATION; MECHANISMS; DISEASE; ABUSE AB Marijuana is the most widely used illicit substance in the United States. Cardiovascular complications in association with marijuana use have been reported during the past three decades. In view of the elevated public interest in this drug's role in pharmacotherapy in the recent years and the aging population of long-term marijuana users from the late 1960s, encounters with marijuana-related cardiovascular adversities may be silently on the rise. The purpose of this article is to increase awareness of the potential of marijuana to lead to cardiovascular disease. Here, we will discuss the physiologic effects of marijuana and include a comprehensive review of the studies and case reports that provide supportive evidence for marijuana as a trigger of adverse cardiovascular events, including tachyarrhythmias, acute coronary syndrome, vascular complications, and even congenital heart defects. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Creighton Univ, Sch Med, Cardiac Ctr, Dept Med,Div Cardiol, Omaha, NE 68131 USA. RP Aryana, A (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St GRB 109, Boston, MA 02114 USA. EM aaryana@partners.org; mark.williams@cardiac.creighton.edu NR 43 TC 64 Z9 65 U1 1 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAY 31 PY 2007 VL 118 IS 2 BP 141 EP 144 DI 10.1016/j.ijcard.2006.08.001 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 171NN UT WOS:000246742800002 PM 17005273 ER PT J AU Tahiliani, M Mei, PC Fang, R Leonor, T Rutenberg, M Shimizu, F Li, J Rao, A Shi, YJ AF Tahiliani, Mamta Mei, Pinchao Fang, Rui Leonor, Thiago Rutenberg, Michael Shimizu, Fumiko Li, Jing Rao, Anjana Shi, Yujiang TI The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation SO NATURE LA English DT Article ID RESTRICTIVE SILENCER FACTOR; DOMAIN-CONTAINING PROTEINS; TRANSCRIPTIONAL REGULATION; CO-REPRESSOR; CHANNEL; JMJC; EXPRESSION; DISORDERS; MUTATIONS; EPILEPSY AB Gene transcription is critically influenced by chromatin structure and the modification status of histone tails(1). Methylation of lysine residues in histone tails is dynamically regulated by the opposing activities of histone methyltransferases and histone demethylases(2). Here we show that JARID1C/SMCX, a JmjC-domain-containing protein implicated in X-linked mental retardation and epilepsy(3,4), possesses H3K4 tri-demethylase activity and functions as a transcriptional repressor. An SMCX complex isolated from HeLa cells contains additional chromatin modifiers (the histone deacetylases HDAC1 and HDAC2, and the histone H3K9 methyltransferase G9a) and the transcriptional repressor REST(5), suggesting a direct role for SMCX in chromatin dynamics and REST-mediated repression. Chromatin immunoprecipitation reveals that SMCX and REST co-occupy the neuron-restrictive silencing elements in the promoters of a subset of REST target genes. RNA-interference-mediated depletion of SMCX derepresses several of these targets and simultaneously increases H3K4 trimethylation at the sodium channel type 2A (SCN2A) and synapsin I (SYN1) promoters. We propose that loss of SMCX activity impairs REST-mediated neuronal gene regulation, thereby contributing to SMCX-associated X-linked mental retardation. C1 Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Brigham & Womens Hosp, BCMP, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA. RP Shi, YJ (reprint author), Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM yujiang_shi@hms.harvard.edu OI Mei, Pinchao/0000-0002-1564-0372; Li, Jing/0000-0001-7699-4249 NR 38 TC 245 Z9 255 U1 3 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 31 PY 2007 VL 447 IS 7144 BP 601 EP + DI 10.1038/nature05823 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172YZ UT WOS:000246842000051 PM 17468742 ER PT J AU Stowell, CP Gelfand, JA Shepard, JO Kratz, A Nundy, S AF Stowell, Christopher P. Gelfand, Jeffrey A. Shepard, Jo-Anne O. Kratz, Alexander Nundy, Surajit TI A woman with relapsing fevers and recent onset of dyspnea - Recurrent, fulminant babesiosis in an asplenic patient SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BOVIS-INFECTED ERYTHROCYTES; EXCHANGE-TRANSFUSION; BLOOD-DONORS; MALARIA; CLINDAMYCIN; PARASITEMIA; MICROTI; QUININE C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Stowell, CP (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. NR 26 TC 18 Z9 18 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 31 PY 2007 VL 356 IS 22 BP 2313 EP 2319 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 172PO UT WOS:000246816500012 PM 17538091 ER PT J AU Shih, VE AF Shih, Vivian E. TI Alternative-pathway therapy for hyperammonemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NITROGEN-EXCRETION; UREA SYNTHESIS; INBORN-ERRORS C1 Massachusetts Gen Hosp, Amino Acid Disorder Lab, Boston, MA 02114 USA. RP Shih, VE (reprint author), Massachusetts Gen Hosp, Amino Acid Disorder Lab, Boston, MA 02114 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 31 PY 2007 VL 356 IS 22 BP 2321 EP 2322 DI 10.1056/NEJMe078075 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 172PO UT WOS:000246816500013 PM 17538092 ER PT J AU Tsokas, P Ma, T Iyengar, R Landau, EM Blitzer, RD AF Tsokas, Panayiotis Ma, Tao Iyengar, Ravi Landau, Emmanuel M. Blitzer, Robert D. TI Mitogen-activated protein kinase upregulates the dendritic translation machinery in long-term potentiation by controlling the mammalian target of rapamycin pathway SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mammalian target of rapamycin; mitogen-activated protein kinase; dendrites; ERK; hippocampus; LTP; protein synthesis; synaptic plasticity ID CYTOPLASMIC POLYADENYLATION ELEMENT; MESSENGER-RNA TRANSLATION; HIPPOCAMPAL CA1 REGION; RIBOSOMAL S6 KINASE; SYNAPTIC PLASTICITY; LATE-PHASE; SIGNALING PATHWAY; TUBEROUS SCLEROSIS; PYRAMIDAL CELLS; PHOSPHATIDYLINOSITOL 3-KINASE AB Protein synthesis is required for persistent forms of synaptic plasticity, including long-term potentiation (LTP). A key regulator of LTP-related protein synthesis is mammalian target of rapamycin (mTOR), which is thought to modulate translational capacity by facilitating the synthesis of particular components of the protein synthesis machinery. Recently, extracellularly regulated kinase (ERK) also was shown to mediate plasticity-related translation, an effect that may involve regulation of the mTOR pathway. We studied the interaction between the mTOR and ERK pathways in hippocampal LTP induced at CA3 -CA1synapses by high-frequency synaptic stimulation (HFS). Within minutes after HFS, the expression of multiple translational proteins, the synthesis of which is under the control of mTOR, increased in area CA1 stratum radiatum. This upregulation was detected in pyramidal cell dendrites and was blocked by inhibitors of the ERK pathway. In addition, ERK mediated the stimulation of mTOR by HFS. The possibility that ERK regulates mTOR by acting at a component further upstream in the phosphatidylinositide 3-kinase (PI3K) -mTOR pathway was tested by probing the phosphorylation of p90-S6 kinase, phosphoinositide-dependent kinase 1 (PDK1), and Akt. ERK inhibitors blocked HFS-induced phosphorylation of all three proteins at sites implicated in the regulation of mTOR. Moreover, a component of basal and HFS-induced ERK activity depended on PI3K, indicating that mTOR-mediated protein synthesis in LTP requires coincident and mutually dependent activity in the PI3K and ERK pathways. The role of ERK in regulating PDK1 and Akt, with their extensive effects on cellular function, has important implications for the coordinated response of the neuron to LTP-inducing stimulation. C1 Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Psychiat Serv, Bronx, NY 10463 USA. RP Blitzer, RD (reprint author), Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, Box 1215,1 Gustave Levy Pl, New York, NY 10029 USA. EM robert.blitzer@mssm.edu FU NIDA NIH HHS [DA015863]; NIGMS NIH HHS [GM54508] NR 82 TC 109 Z9 109 U1 1 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 30 PY 2007 VL 27 IS 22 BP 5885 EP 5894 DI 10.1523/JNEUROSCI.4548-06.2007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 175YA UT WOS:000247048700008 PM 17537959 ER PT J AU Putnam, KM Kring, AM AF Putnam, Katherine M. Kring, Ann M. TI Accuracy and intensity of posed emotional expressions in unmedicated schizophrenia patients: Vocal and facial channels SO PSYCHIATRY RESEARCH LA English DT Article DE posed emotion; schizophrenia; emotional expression; flat affect; negative symptoms ID BRAIN-DAMAGED PATIENTS; DEPRESSED-PATIENTS; FLAT AFFECT; NEGATIVE SYMPTOMS; STARTLE REFLEX; PATIENTS SHOW; EXPRESSIVENESS; RECOGNITION; MODULATION; DEFICIT AB This study investigated the ability of schizophrenia patients to volitionally display various emotional expressions. Accuracy and intensity of facial and vocal emotional expression were rated in 26 unmedicated male schizophrenia patients and 20 non-patient male controls while posing emotional facial and vocal expressions. Results indicate that schizophrenia patients, compared to nonpatient controls, had deficits in their ability to portray some, but not all, emotions. Accuracy and intensity of posed facial and vocal expressions were inversely correlated with negative symptoms in the patient group. We conclude that observable flattened affect in schizophrenia during posed expression is not evident across all emotions. Furthermore, substantial disruption in the ability to portray posed emotions may be largely driven by the presence of negative symptoms. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. RP Putnam, KM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. EM Katherine.Putnam@va.gov FU NIMH NIH HHS [MH44116] NR 48 TC 13 Z9 13 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 30 PY 2007 VL 151 IS 1-2 BP 67 EP 76 DI 10.1016/j.psychres.2006.09.010 PG 10 WC Psychiatry SC Psychiatry GA 185WF UT WOS:000247740400008 PM 17368792 ER PT J AU Horan, WP Ventura, J Mintz, J Kopelowicz, A Wirshing, D Christian-Herman, J Foy, D Liberman, RP AF Horan, William P. Ventura, Joseph Mintz, Jim Kopelowicz, Alex Wirshing, Donna Christian-Herman, Jennifer Foy, David Liberman, Robert P. TI Stress and coping responses to a natural disaster in people with schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE schizophrenia; bipolar disorder; stress; disaster; coping; methodology ID RECENT-ONSET SCHIZOPHRENIA; SEVERE MENTAL-ILLNESS; DAILY-LIFE STRESS; EVENT SCALE; BIPOLAR DISORDER; SOCIAL SUPPORT; IMPACT; EARTHQUAKE; SURVIVORS; RELAPSE AB Investigations of how individuals with schizophrenia differ from non-patients in their responses to stressful life events are subject to the criticism that any between-group differences might merely reflect differences in the types of stressful events that each group experiences. This report presents new analyses of data collected from schizophrenia patients (n=96), bipolar disorder patients (n=18), and healthy controls (n= 18) immediately after the Northridge Earthquake that struck Southern California in 1994, a natural experiment that confronted all groups with the same stressful event. Participants completed the, Impact of Events Scale (IES; [Horowitz, M.J., Wilner, N., Alvarez, W., 1979. Impact of Events Scale. A measure of subjective stress. Psychosomatic Medicine 41, 209-218]) at I week and 5 weeks post-earthquake. At the 5-week follow-up, measures of coping, social support, and self-esteem were also completed. Both patient groups reported higher IES avoidance symptoms than controls immediately after the earthquake. The schizophrenia group also reported lower approach coping, self-esteem, and social support than controls, with the bipolar group reporting intermediate levels. Within the schizophrenia group, higher levels of avoidance coping predicted higher residual stress symptoms at follow-up. Results support the validity of prior reports of altered responses to stressful life events in schizophrenia and demonstrate the clinical relevance of individual differences in coping among affected individuals. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. San Fernando Mental Hlth Ctr, Los Angeles, CA USA. Pepperdine Univ, Los Angeles, CA USA. RP Horan, WP (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 UCLA Med Plaza,Room 2240, Los Angeles, CA 90095 USA. EM horan@ucla.edu OI kopelowicz, alex/0000-0002-1728-4105 NR 45 TC 25 Z9 27 U1 3 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 30 PY 2007 VL 151 IS 1-2 BP 77 EP 86 DI 10.1016/j.psychres.2006.10.009 PG 10 WC Psychiatry SC Psychiatry GA 185WF UT WOS:000247740400009 PM 17382405 ER PT J AU Fraguas, R Marci, C Fava, M Iosifescu, DV Bankier, B Loh, R Dougherty, DD AF Fraguas, Renerio, Jr. Marci, Carl Fava, Maurizio Iosifescu, Dan V. Bankier, Bettina Loh, Rebecca Dougherty, Darin D. TI Autonomic reactivity to induced emotion as potential predictor of response to antidepressant treatment SO PSYCHIATRY RESEARCH LA English DT Article DE depressive disorders; heart rate variability; treatment; skin conductance; automatic system; serotonin reuptake inhibitors ID HEART-RATE-VARIABILITY; POSITRON-EMISSION-TOMOGRAPHY; SCRIPT-DRIVEN IMAGERY; MAJOR DEPRESSION; DISORDER; DISEASE; ANGER AB Distinct factors have been identified as potential predictors of antidepressant treatment response. Although autonomic function changes have been described in depressive subjects, their value as predictors of antidepressant response has not been systematically evaluated. Eight un-medicated patients with major depressive order (MDD) have their skin conductance (SC) and heart rate variability (HRV) measured at basal condition and during four induced emotional states: happy, angry, sad and neutral. The high frequency (HE) and low frequency (LF) power parameters of HRV were assessed. Subsequently, patients were treated with fluoxetine 20 mg/day for 8 weeks. The antidepressant response was measured with the Beck Depression Inventory (BDI). The BDI percentage reduction correlated significantly with HRV responses during sad condition in LF power, and during happy condition with LF/HF ratio. The BDI percentage reduction also correlated significantly with HR responses in happy and in neutral conditions, and also with SC responses in neutral condition. These preliminary findings indicate that automatic responses to induced emotions may predict antidepressant response in MDD patients. Confirmatory studies are warranted. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fraguas, R (reprint author), Univ Sao Paulo, Hosp Clin, Fac Med, Inst Psiquiatria, Rua Ovidio Pires Campos S-N, BR-05034010 Sao Paulo, Brazil. EM rfraguas@partners.org FU NIMH NIH HHS [MH017350] NR 15 TC 20 Z9 20 U1 2 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 30 PY 2007 VL 151 IS 1-2 BP 169 EP 172 DI 10.1016/j.psychres.2006.08.008 PG 4 WC Psychiatry SC Psychiatry GA 185WF UT WOS:000247740400021 PM 17360044 ER PT J AU Zhang, ZG Sun, LQ Sun, HG Finkelstein, DA AF Zhang, Zhigang Sun, Liuquan Sun, Hanguo Finkelstein, Dianne A. TI Regression analysis of failure time data with informative interval censoring SO STATISTICS IN MEDICINE LA English DT Article DE failure time data; regression analysis; informative interval censoring; proportional hazards frailty model; EM algorithm ID PROPORTIONAL HAZARDS MODEL; EM ALGORITHM AB Interval censoring arises when a subject misses prescheduled visits at which the failure is to be assessed. Most existing approaches for analysing interval-censored failure time data assume that the censoring mechanism is independent of the true failure time. However, there are situations where this assumption may not hold. In this paper, we consider such a situation in which the dependence structure between the censoring variables and the failure time can be modelled through some latent variables and a method for regression analysis of failure time data is proposed. The method makes use of the proportional hazards frailty model and an EM algorithm is presented for estimation. Finite sample properties of the proposed estimators of regression parameters are examined through simulation studies and we illustrate the method with data from an AIDS study. Copyright (C) 2006 John Wiley & Sons, Ltd. C1 Oklahoma State Univ, Dept Stat, Stillwater, OK 74078 USA. Chinese Acad Sci, Inst Appl Math Sci, Beijing 100080, Peoples R China. Univ Missouri, Dept Stat, Columbia, MO 65211 USA. Harvard Univ, Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Zhang, ZG (reprint author), Oklahoma State Univ, Dept Stat, 301 Math Sci Bldg, Stillwater, OK 74078 USA. EM zhigang.zhang@okstate.edu FU NCI NIH HHS [R01-CA74302-08]; NIAID NIH HHS [R01-AI043353-08] NR 20 TC 13 Z9 13 U1 1 U2 12 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 30 PY 2007 VL 26 IS 12 BP 2533 EP 2546 DI 10.1002/sim.2721 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 167CI UT WOS:000246428000007 PM 17072823 ER PT J AU Hylek, EM Evans-Molina, C Shea, C Henault, LE Regan, S AF Hylek, Elaine M. Evans-Molina, Carmella Shea, Carol Henault, Lori E. Regan, Susan TI Major Hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation SO CIRCULATION LA English DT Article DE anticoagulants; atrial fibrillation; hemorrhage; stroke ID ORAL ANTICOAGULANT-THERAPY; RANDOMIZED CONTROLLED-TRIAL; STROKE PREVENTION; BLEEDING COMPLICATIONS; ANTITHROMBOTIC THERAPY; RISK-FACTORS; INTRACRANIAL HEMORRHAGE; MEDICARE BENEFICIARIES; CLINICAL-PRACTICE; VASCULAR EVENTS AB Background - Warfarin is effective in the prevention of stroke in atrial fibrillation but is under used in clinical care. Concerns exist that published rates of hemorrhage may not reflect real-world practice. Few patients >= 80 years of age were enrolled in trials, and studies of prevalent use largely reflect a warfarin-tolerant subset. We sought to define the tolerability of warfarin among an elderly inception cohort with atrial fibrillation. Methods and Results - Consecutive patients who started warfarin were identified from January 2001 to June 2003 and followed for 1 year. Patients had to be >= 65 years of age, have established care at the study institution, and have their warfarin managed on- site. Outcomes included major hemorrhage, time to termination of warfarin, and reason for discontinuation. Of 472 patients, 32% were >= 80 years of age, and 91% had >= 1 stroke risk factor. The cumulative incidence of major hemorrhage for patients >= 80 years of age was 13.1 per 100 person- years and 4.7 for those < 80 years of age (P = 0.009). The first 90 days of warfarin, age >= 80 years, and international normalized ratio (INR) >= 4.0 were associated with increased risk despite trial-level anticoagulation control. Within the first year, 26% of patients >= 80 years of age stopped taking warfarin. Perceived safety issues accounted for 81% of them. Rates of major hemorrhage and warfarin termination were highest among patients with CHADS(2) scores ( an acronym for congestive heart failure, hypertension, age >= 75, diabetes mellitus, and prior stroke or transient ischemic attack) of >= 3. Conclusions - Rates of hemorrhage derived from younger noninception cohorts underestimate the bleeding that occurs in practice. This finding coupled with the short-term tolerability of warfarin likely contributes to its underutilization. Stroke prevention among elderly patients with atrial fibrillation remains a challenging and pressing health concern. C1 Boston Univ, Sch Med, Boston Med Ctr,Dept Med, Res Unit,Sect Gen Internal Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Univ Virginia, Dept Med, Charlottesville, VA USA. RP Hylek, EM (reprint author), Boston Univ, Sch Med, Boston Med Ctr,Dept Med, Res Unit,Sect Gen Internal Med, 91 E Concord St,Suite 200, Boston, MA 02118 USA. EM ehylek@bu.edu NR 48 TC 547 Z9 581 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP 2689 EP 2696 DI 10.1161/CIRCULATIONHA.106.653048 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600003 PM 17515465 ER PT J AU Reddy, VY Neuzil, P Malchano, ZJ Vijaykumar, R Cury, R Abbara, S Weichet, J McPherson, CD Ruskin, JN AF Reddy, Vivek Y. Neuzil, Petr Malchano, Zachary J. Vijaykumar, Ragu Cury, Ricardo Abbara, Suhny Weichet, Jiri McPherson, Christina D. Ruskin, Jeremy N. TI View-synchronized robotic image-guided therapy for atrial fibrillation ablation - Experimental validation and clinical feasibility SO CIRCULATION LA English DT Article; Proceedings Paper CT 27th Annual Scientific Session of the Heart-Rhythm-Society CY MAY 17-20, 2006 CL Boston, MA SP Heart Rhythm Soc DE catheter ablation; tomography, x-ray computed; fibrillation; imaging; mapping ID MAGNETIC NAVIGATION; CATHETER ABLATION; PULMONARY VEIN; SYSTEM; EXPERIENCE; EFFICACY; IMPACT; HEART AB Background - A robotic catheter navigation system has been developed that provides a significant degree of freedom of catheter movement. This study examines the feasibility of synchronizing this robotic navigation system with electroanatomic mapping and 3-dimensional computed tomography imaging to perform view- synchronized left atrial (LA) ablation. Methods and Results - This study consisted of a porcine experimental validation phase (9 animals) and a clinical feasibility phase (9 atrial fibrillation patients). Preprocedural computed tomography images were reconstructed to provide 3-dimensional surface models of the LA pulmonary veins and aorta. Aortic electroanatomic mapping was performed manually, followed by registration with the corresponding computed tomography aorta image using custom software. The mapping catheter was remotely manipulated with the robotic navigation system within the registered computed tomography image of the LA pulmonary veins. The point-to-surface error between the LA electroanatomic mapping data and the computed tomography image was 2.1 +/- 0.7 and 1.6 +/- 0.1 mm in the preclinical and clinical studies, respectively. The catheter was remotely navigated into all pulmonary veins, the LA appendage, and circumferentially along the mitral valve annulus. In 7 of 9 animals, circumferential radiofrequency ablation lesions were applied periostially to ablate 11 pulmonary veins. In patients, all of the pulmonary veins were remotely electrically isolated in an extraostial fashion. Adjunctive ablation included superior vena cava isolation in 6 patients, cavotricuspid isthmus ablation in 5 patients, and ablation of sites of complex fractionated activity and atypical LA flutters in 3 patients. Conclusions - This study demonstrates the safety and feasibility of an emerging paradigm for atrial fibrillation ablation involving the confluence of 3 technologies: 3-dimensional imaging, electroanatomic mapping, and remote robotic navigation. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Homolka Hosp, Prague, Czech Republic. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM vreddy@partners.org FU NHLBI NIH HHS [K23 HL68064] NR 14 TC 50 Z9 50 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP 2705 EP 2714 DI 10.1161/CIRCULATIONHA.106.677369 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600005 PM 17502570 ER PT J AU Ahmad, H Jones, PG Buchanan, DM Ho, PM Decker, C Spertus, JA AF Ahmad, Homaa Jones, Philip G. Buchanan, Donna M. Ho, P. M. Decker, Carole Spertus, John A. TI Medication use post acute myocardial infarction: A latent class analysis SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Denver VA Med Ctr, Denver, CO USA. Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E587 EP E587 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600185 ER PT J AU Helfrich, CD Sharp, ND Pineros, SL Lowy, E McDermott, KA Sales, AE Larsen, GC Fihn, SD AF Helfrich, Christian D. Sharp, Nancy D. Pineros, Sandra L. Lowy, Elliott McDermott, Kelly A. Sales, Anne E. Larsen, Greg C. Fihn, Stephan D. TI How veterans health administration facilities have changed practices to improve care for patients with acute coronary syndromes SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Alberta, Edmonton, AB T6G 2M7, Canada. VA Med Ctr, Portland, OR USA. RI Sales, Anne/D-9678-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E591 EP E591 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600200 ER PT J AU Ho, PM Magid, DJ Shetterly, SM Olson, KO Peterson, PN Masoudi, FA Rumsfeld, JS AF Ho, P. Michael Magid, David J. Shetterly, Susan M. Olson, Kari O. Peterson, Pamela N. Masoudi, Frederick A. Rumsfeld, John S. TI The importance of therapy intensification and medication non-adherence for blood pressure control in patients with coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Denver VA Med Ctr, Denver, CO USA. Kaiser Permanente, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E580 EP E580 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600151 ER PT J AU Ho, PM Fihn, SD Wang, L Bryson, CL Lowy, E Maynard, C Magid, DJ Peterson, ED Rumsfeld, JS AF Ho, P. Michael Fihn, Stephan D. Wang, Li Bryson, Chris L. Lowy, Elliott Maynard, Charles Magid, David J. Peterson, Eric D. Rumsfeld, John S. TI The impact of clopidogrel use on long-term outcomes following stent implantation for acute coronary syndrome in the VHA SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Denver VA Med Ctr, Denver, CO USA. Puget Sound VA Healthcare Syst, Seattle, WA USA. Kaiser Pemanente Colorado, Denver, CO USA. Duke Clin Res Inst, Durham, NC USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E573 EP E573 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600121 ER PT J AU Jiang, YD Liang, YF Helmy, M Kimball, WR Todres, ID Kacmarek, RM Zapol, WM AF Jiang, Yandong Liang, Yafen Helmy, Mohamed Kimball, William R. Todres, I. David Kacmarek, Robert M. Zapol, Warren M. TI Nasal ventilation is more efficient than oral ventilation in unconscious apneic adult patients SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E600 EP E600 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600244 ER PT J AU Larsen, GC McFalls, E Rumsfeld, JS Pineros, SL Wang, L Zoble, RG Tenney, S Bradley, M Morris, K Steinberg, S Shaikh, M Fihn, SD AF Larsen, Greg C. McFalls, Edward Rumsfeld, John S. Pineros, Sandra L. Wang, Li Zoble, Robert G. Tenney, Scott Bradley, Mark Morris, Kenneth Steinberg, Sidney Shaikh, Muhammed Fihn, Stephan D. TI Is quality of care for unstable angina comparable to that for acute myocardial infarction in the veterans health administration? SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 VA Med Ctr, Portland, OR USA. VA Med Ctr, Minneapolis, MN USA. VA Med Ctr, Denver, CO USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. James A Haley Vet Hosp, Tampa, FL 33612 USA. VA Med Ctr, Sheridan, WY USA. VA Med Ctr, Roseburg, OR USA. VA Med Ctr, Durham, NC USA. WG Bill Hefner VA Med Ctr, Salisbury, NC USA. VA Med Ctr, Fargo, ND USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E598 EP E599 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600235 ER PT J AU Lichtman, JH Wang, YF Curtis, JP Allen, NB Watanabe, E Shaw, LJ Rumsfeld, JS Krumholz, HM AF Lichtman, Judith H. Wang, Yongfei Curtis, Jeptha P. Allen, Norrina B. Watanabe, Emi Shaw, Leslee J. Rumsfeld, John S. Krumholz, Harlan M. TI Conventional risk factors are highest for minority women presenting with myocardial infarction: Results from the ACC-NCDR registry SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Yale Univ, Sch Med, New Haven, CT USA. Emory Univ, Sch Med, Atlanta, GA USA. Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E554 EP E554 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600037 ER PT J AU Lichtman, JH Wang, YF Curtis, JP Watanabe, E Allen, NB Shaw, LJ Rumsfeld, JS Krumholz, HM AF Lichtman, Judith H. Wang, Yongfei Curtis, Jeptha P. Watanabe, Emi Allen, Norrina B. Shaw, Leslee J. Rumsfeld, John S. Krumholz, Harlan M. TI Young women undergoing elective PCI procedures have higher complication rates than similarly aged men: Results from the ACC-NCDR registry SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Yale Univ, Sch Med, New Haven, CT USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E578 EP E578 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600141 ER PT J AU Luther, SA Magid, DJ Ho, PM Brand, DW Peterson, PN Ross, C Rumsfeld, JS Frederick, MA AF Luther, Stacie A. Magid, David J. Ho, P. Michael Brand, David W. Peterson, Pamela N. Ross, Colleen Rumsfeld, John S. Frederick, Masoudi A. TI Sex differences in evaluation and treatment after exercise stress testing SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Kaiser Permanente, Denver, CO USA. Denver VA Med Ctr, Denver, CO USA. Denver Hlth Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E587 EP E587 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600182 ER PT J AU Pineros, SL Rumsfeld, JS Larsen, GC Wang, L McFalls, E Zoble, RG Tenney, S Bradley, M Steinberg, S Shaikh, M Morris, K Fihn, SD AF Pineros, Sandra L. Rumsfeld, John S. Larsen, Greg C. Wang, Li McFalls, Edward Zoble, Robert G. Tenney, Scott Bradley, Mark Steinberg, Sidney Shaikh, Muhammed Morris, Kenneth Fihn, Stephan D. TI Outcomes of acute coronary syndrome patients who report in-hospital depressive symptoms in veterans health administration SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. VA Med Ctr, Denver, CO USA. VA Med Ctr, Portland, OR USA. VA Med Ctr, Minneapolis, MN USA. James A Haley Vet Hosp, Tampa, FL USA. VA Med Ctr, Sheridan, WY USA. VA Med Ctr, Roseburg, OR USA. WG Bill Hefner VA Med Ctr, Salisbury, NC USA. VA Med Ctr, Fargo, ND USA. VA Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E595 EP E595 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600220 ER PT J AU Ramanath, VS Nienaber, CA Evangelista, A Oh, J Llovet, A Beckman, J Hirsch, A Harris, K Cooper, JV Tsai, TT Eagle, KA Isselbacher, E Froehlich, JB AF Ramanath, Vijay S. Nienaber, Christoph A. Evangelista, Arturo Oh, Jae Llovet, Alfredo Beckman, Joshua Hirsch, Alan Harris, Kevin Cooper, Jeanna V. Tsai, Thomas T. Eagle, Kim A. Isselbacher, Eric Froehlich, James B. TI Risk factors, management, and outcomes of recurrent acute aortic dissection in patients from the international registry of acute aortic dissection (IRAD) SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Rostock, Rostock, Germany. Univ Barcelona, Gen Hosp, Barcelona, Spain. Mayo Clin, Rochester, MN USA. Hosp Univ Madrid, Madrid, Spain. Brigham & Womens Hosp, Boston, MA 02115 USA. Minneapolis Heart Inst, Minneapolis, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E557 EP E557 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600051 ER PT J AU Smith, EE Schwamm, LH Watkins, J Hernandez, A AF Smith, Eric E. Schwamm, Lee H. Watkins, Jerry Hernandez, Adrian CA GWTG Steering Comm Investigators TI Comparison of hospital-based hemorrhagic and ischemic acute stroke care in get with the guidelines stroke SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Durham, NC USA. Amer Heart Assoc, Dallas, TX USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E560 EP E560 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600062 ER PT J AU Wang, TY Xiao, L Alexander, KP Kosiborod, MN Rumsfeld, JS Spertus, JA Peterson, ED AF Wang, Tracy Y. Xiao, Lan Alexander, Karen P. Kosiborod, Mikhail N. Rumsfeld, John S. Spertus, John A. Peterson, Eric D. TI Trends in antiplatelet therapy use following discharge among acute myocardial infarction patients with in-hospital bleeding SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Duke Univ, Med Ctr, Durham, NC 27706 USA. Duke Clin Res Inst, Durham, NC USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Denver VA Med Ctr, Denver, CO USA. Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E575 EP E575 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600128 ER PT J AU Weintraub, WS Zhang, ZF Kolm, P Jurkovitz, C Hartigan, P Culler, S Becker, E Lewis, C Veledar, E Bowen, J Dunbar, SB Deaton, C Kaufman, S Maron, D Teo, K O'Rourke, R Goeree, R Barnett, P Spertus, J Boden, WE AF Weintraub, William S. Zhang, Zefeng Kolm, Paul Jurkovitz, Claudine Hartigan, Pamela Culler, Steven Becker, Edmund Lewis, Cheryl Veledar, Emir Bowen, Jim Dunbar, Sandra B. Deaton, Christi Kaufman, Stanley Maron, David Teo, Koon O'Rourke, Robert Goeree, Ron Barnett, Paul Spertus, John Boden, William E. TI Quality-of-life and economic outcomes in the Clinical Outcomes Utilizing Percutaneous coronary Revascularization and Aggressive Guideline-driven Drug Evaluation (COURAGE) trial SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Christiana Care Hlth Syst, Newark, DE USA. W Haven Vet Affairs Med Ctr, West Haven, CT USA. Emory Univ, Atlanta, GA 30322 USA. Univ Manchester, Manchester, Lancs, England. Epimetrics, San Francisco, CA USA. Vanderbilt Univ, Nashville, TN USA. McMaster Univ, Hamilton, ON, Canada. Vet Adm Med Ctr, San Antonio, TX USA. Vet Adm Med Ctr, Palo Alto, CA 94304 USA. Mid Amer Heart Inst, Kansas City, MO USA. Kaleida Hlth Syst, Buffalo, NY USA. RI Deaton, Christi/F-6485-2010; Veledar, Emir/K-2808-2012 OI Veledar, Emir/0000-0002-3831-5433 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E551 EP E551 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600022 ER PT J AU Welch, VL Parashar, S Reid, KJ Lichtman, JH Ahmad, H Spertus, JA Rumsfeld, JS Vaccarino, V AF Welch, Verna L. Parashar, Susmita Reid, Kimberly J. Lichtman, Judith H. Ahmad, Homaa Spertus, John A. Rumsfeld, John S. Vaccarino, Viola TI Depression partially explains worse quality-of-life outcomes of women versus men following acute myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 8th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY MAY 09-11, 2007 CL Washington, DC C1 Morehouse Sch Med, Atlanta, GA 30310 USA. Emory Univ, Atlanta, GA 30322 USA. St Lukes Hlth Syst, Mid Amer Heart Inst, Kansas City, MO USA. Yale Univ, New Haven, CT USA. Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA. Denver VA Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2007 VL 115 IS 21 BP E553 EP E553 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 172LA UT WOS:000246804600031 ER PT J AU Kolodgie, FD Narula, J Yuan, C Burke, AP Finn, AV Virmani, R AF Kolodgie, Frank D. Narula, Jagat Yuan, Chun Burke, Allen P. Finn, Aloke V. Virmani, Renu TI Elimination of neoangiogenesis for plaque stabilization - Is there a role for local drug therapy? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; RED-BLOOD-CELLS; CORONARY-ARTERY-DISEASE; INTRAPLAQUE HEMORRHAGE; ATHEROSCLEROTIC PLAQUES; VASA VASORUM; EXPERIMENTAL HYPERCHOLESTEROLEMIA; VASCULAR-PERMEABILITY; ANGIOGENESIS; NEOVASCULARIZATION AB Emerging data suggest that intraplaque hemorrhage is critical in promoting atherosclerotic lesion instability. Because red blood cell membranes are a rich source of free cholesterol and accumulated red blood cells within plaques promote inflammation, intraplaque hemorrhage is associated with expansion of the necrotic core. Plaque hemorrhage results from the development of immature neointimal vasa vasorum. Therefore, it is proposed that molecular therapies designed to eliminate pathologic neovascularization within developing lesions will interrupt the process of hemorrhage and decrease the rate of necrotic core expansion. The elimination of intraplaque neovascularization would involve targeting of pre-existing and new vessel development. The concept of vascular regression has met some success in other neovascular-dependent diseases, including macular degeneration and malignancies. The efficacy of this novel approach is dependent on gaining critical knowledge of the environment required to support development and maturation of the vasa vasorum within varying plaque types. A multitargeted approach involving selective local antiangiogenic agents should contribute to prevention of plaque progression and its clinical consequences. C1 CVPath Inst, Gaithersburg, MD 20878 USA. Univ Calif Irvine, Irvine, CA USA. Univ Washington, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Virmani, R (reprint author), CVPath Inst, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org FU NHLBI NIH HHS [R01 HL61799-02] NR 61 TC 63 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 29 PY 2007 VL 49 IS 21 BP 2093 EP 2101 DI 10.1016/j.jacc.2006.10.083 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 173SU UT WOS:000246893600004 PM 17531658 ER PT J AU Schacter, DL Addis, DR AF Schacter, Daniel L. Addis, Donna Rose TI The cognitive neuroscience of constructive memory: remembering the past and imagining the future SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Royal-Society Discussion Meeting on Mental Processes in the Human Brain CY OCT 16-17, 2006 CL Royal Soc, London, ENGLAND HO Royal Soc DE constructive memory; false recognition; mental simulation; neuroimaging; amnesia; Alzheimer's disease ID MENTAL TIME-TRAVEL; MEDIAL TEMPORAL-LOBE; COMPLEMENTARY-LEARNING-SYSTEMS; POSITRON-EMISSION-TOMOGRAPHY; PERCEPTUAL FALSE RECOGNITION; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; AMNESIC PATIENTS; PHENOMENAL CHARACTERISTICS; AUTOBIOGRAPHICAL MEMORY AB Episodic memory is widely conceived as a fundamentally constructive, rather than reproductive, process that is prone to various kinds of errors and illusions. With a view towards examining the functions served by a constructive episodic memory system, we consider recent neuropsychological and neuroimaging studies indicating that some types of memory distortions reflect the operation of adaptive processes. An important function of a constructive episodic memory is to allow individuals to simulate or imagine future episodes, happenings and scenarios. Since the future is not an exact repetition of the past, simulation of future episodes requires a system that can draw on the past in a manner that flexibly extracts and recombines elements of previous experiences. Consistent with this constructive episodic simulation hypothesis, we consider cognitive, neuropsychological and neuroimaging evidence showing that there is considerable overlap in the psychological and neural processes involved in remembering the past and imagining the future. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Schacter, DL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM dls@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061; Addis, Donna Rose/0000-0002-6231-1491 FU NIA NIH HHS [AG08441, R01 AG008441, R37 AG008441]; NIMH NIH HHS [MH060941, R01 MH060941] NR 117 TC 485 Z9 495 U1 28 U2 103 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD MAY 29 PY 2007 VL 362 IS 1481 BP 773 EP 786 DI 10.1098/rstb.2007.2087 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 155SS UT WOS:000245599000003 PM 17395575 ER PT J AU Le, XN Langenau, DM Keefe, MD Kutok, JL Neuberg, DS Zon, LI AF Le, Xiuning Langenau, David M. Keefe, Matthew D. Kutok, Jeffery L. Neuberg, Donna S. Zon, Leonard I. TI Heat shock-inducible Cre/Lox approaches to induce diverse types of tumors and hyperplasia in transgenic zebrafish SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE myeloproliferative disorder; RAS; rhabdomyosarcoma; intestine; malignant peripheral nerve sheath tumor ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ONCOGENIC K-RAS; SOMATIC ACTIVATION; DANIO-RERIO; CONDITIONAL EXPRESSION; GENE-EXPRESSION; MOUSE MODELS; IN-VIVO; CANCER; MICE AB RAS family members are among the most frequently mutated oncogenes in human cancers. Given the utility of zebrafish in both chemical and genetic screens, developing RAS-induced cancer models will make large-scale screens possible to understand further the molecular mechanisms underlying malignancy. We developed a heat shock-inducible Cre/Lox-mediated transgenic approach in which activated human kRASG12D can be conditionally induced within transgenic animals by heat shock treatment. Specifically, double transgenic fish Tg(B-actin-LoxP-EGFP-LoxP-kRASG12D, hsp70-Cre) developed four types of tumors and hyperplasia after heat shock of whole zebrafish embryos, including rhabdomyosarcoma, myeloproliferative disorder, intestinal hyperplasia, and malignant peripheral nerve sheath tumor. Using ex vivo heat shock and transplantation of whole kidney marrow cells from double transgenic animals, we were able to generate specifically kRASG12D-induced myeloproliferative disorder in recipient fish. This heat shock-inducible recombination approach allowed for the generation of multiple types of RAS-induced tumors and hyperplasia without characterizing tissue-specific promoters. Moreover, these tumors and hyperplasia closely resemble human diseases at both the morphologic and molecular levels. C1 Childrens Hosp, HHMI, Boston, MA 02115 USA. Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, HHMI, 300 Longwood Ave,Karp 7, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu NR 39 TC 100 Z9 106 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 29 PY 2007 VL 104 IS 22 BP 9410 EP 9415 DI 10.1073/pnas.0611302104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 174IN UT WOS:000246935700059 PM 17517602 ER PT J AU Cianferotti, L Cox, M Skorija, K Demay, MB AF Cianferotti, Luisella Cox, Megan Skorija, Kristi Demay, Marie B. TI Vitamin D receptor is essential for normal keratinocyte stem cell function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE alopecia; knockout; Wnt signaling; Lef ID HAIR FOLLICLE MORPHOGENESIS; BETA-CATENIN; KNOCKOUT MICE; TRANSIENT ACTIVATION; ANDROGEN RECEPTOR; SIGNALING PATHWAY; NUCLEAR RECEPTORS; NULL MICE; DIFFERENTIATION; SKIN AB The major physiological role of the vitamin D receptor (VDR) is the maintenance of mineral ion homeostasis. Mutation of the VDR, in humans and mice, results in alopecia. Unlike the effects of the VDR on mineral ion homeostasis, the actions of the VDR that prevent alopecia are ligand-independent. Although absence of the VDR does not prevent the development of a keratinocyte stem cell niche in the bulge region of the hair follicle, it results in an inability of these stem cells to regenerate the lower portion of the hair follicle in vivo and impairs keratinocyte stem cell colony formation in vitro. VDR ablation is associated with a gradual decrease in keratinocyte stem cells, accompanied by an increase in sebaceous activity, a phenotype analogous to that seen with impaired canonical Wnt signaling. Transient gene expression assays demonstrate that the cooperative transcriptional effects of beta-catenin and Lef1 are abolished in keratinocytes isolated from VDR-null mice, revealing a role for the unliganded VDR in canonical Writ signaling. Thus, absence of the VDR impairs canonical Writ signaling in keratinocytes and leads to the development of alopecia due to a defect in keratinocyte stem cells. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK 46974, R01 DK046974] NR 46 TC 77 Z9 83 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 29 PY 2007 VL 104 IS 22 BP 9428 EP 9433 DI 10.1073/pnas.0702884104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 174IN UT WOS:000246935700062 PM 17517646 ER PT J AU Wilson, PWF Meigs, JB Sullivan, L Fox, CS Nathan, DM D'Agostino, RB AF Wilson, Peter W. F. Meigs, James B. Sullivan, Lisa Fox, Caroline S. Nathan, David M. D'Agostino, Ralph B., Sr. TI Prediction of incident diabetes mellitus in middle-aged adults - The Framingham Offspring Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INSULIN-RESISTANCE ATHEROSCLEROSIS; GLUCOSE-TOLERANCE TEST; METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; HIGH-RISK; ALTERNATIVE DEFINITIONS; FASTING GLUCOSE; HEART; MODEL; VALIDATION AB Background: Prediction rules for type 2 diabetes mellitus (T2DM) have been developed, but we lack consensus for the most effective approach. Methods: We estimated the 7-year risk of T2DM in middle-aged participants who had an oral glucose tolerance test at baseline. There were 160 cases of new T2DM, and regression models were used to predict new T2DM, starting with characteristics known to the subject (personal model, ie, age, sex, parental history of diabetes, and body mass index [calculated as the weight in kilograms divided by height in meters squared]), adding simple clinical measurements that included metabolic syndrome traits (simple clinical model), and, finally, assessing complex clinical models that included (1) 2-hour post-oral glucose tolerance test glucose, fasting insulin, and C-reactive protein levels; (2) the Gutt insulin sensitivity index; or (3) the homeostasis model insulin resistance and the homeostasis model insulin resistance beta- cell sensitivity indexes. Discrimination was assessed with area under the receiver operating characteristic curves (AROCs). Results: The personal model variables, except sex, were statistically significant predictors of T2DM (AROC, 0.72). In the simple clinical model, parental history of diabetes and obesity remained significant predictors, along with hyper-tension, low levels of high-density lipoprotein cholesterol, elevated triglyceride levels, and impaired fasting glucose findings but not a large waist circumference (AROC, 0.85). Complex clinical models showed no further improvement in model discriminations (AROC, 0.850-0.854) and were not superior to the simple clinical model. Conclusion: Parental diabetes, obesity, and metabolic syndrome traits effectively predict T2DM risk in a middleaged white population sample and were used to develop a simple T2DM prediction algorithm to estimate risk of new T2DM during a 7-year follow-up interval. C1 Emory Univ, Sch Med, Emory Program Cardiovasc Outcomes Res & Epidemiol, Atlanta, GA 30306 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Wilson, PWF (reprint author), Emory Univ, Sch Med, Emory Program Cardiovasc Outcomes Res & Epidemiol, 1256 Briarcliff Rd,Suite 1N, Atlanta, GA 30306 USA. EM pwwilso@emory.edu OI Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [N01-HC-25195] NR 36 TC 367 Z9 385 U1 0 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 28 PY 2007 VL 167 IS 10 BP 1068 EP 1074 DI 10.1001/archinte.167.10.1068 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 172AE UT WOS:000246775700011 PM 17533210 ER PT J AU Scheer, FAJL Stone, PH Shea, SA AF Scheer, Frank A. J. L. Stone, Peter H. Shea, Steven A. TI Decreased sleep in heart failure: Are medications to blame? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material C1 Brigham & Womens Hosp, Div Sleep Med, Sleep Disorders Res Program, BIDMC, Boston, MA 02115 USA. RP Scheer, FAJL (reprint author), Brigham & Womens Hosp, Div Sleep Med, Sleep Disorders Res Program, BIDMC, 75 Francis St, Boston, MA 02115 USA. EM fscheer@rics.bwh.harvard.edu RI Scheer, Frank/C-2795-2012 FU NHLBI NIH HHS [K24 HL076446-05] NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 28 PY 2007 VL 167 IS 10 BP 1098 EP 1099 DI 10.1001/archinte.167.10.1098-b PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 172AE UT WOS:000246775700016 PM 17533214 ER PT J AU Crunkhorn, S Dearie, F Mantzoros, C Gami, H da Silva, WS Espinoza, D Faucette, R Barry, K Bianco, AC Patti, ME AF Crunkhorn, Sarah Dearie, Farrell Mantzoros, Christos Gami, Hiral da Silva, Wagner S. Espinoza, Daniel Faucette, Ryan Barry, Kristen Bianco, Antonio C. Patti, Mary Elizabeth TI Peroxisome proliferator activator receptor gamma coactivator-1 expression is reduced in obesity - Potential pathogenic role of saturated fatty acids and p38 mitogen-activated protein kinase activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN SKELETAL-MUSCLE; INSULIN-RESISTANCE; GENE-EXPRESSION; ENERGY-EXPENDITURE; TRANSCRIPTIONAL COACTIVATORS; PGC-1-ALPHA TRANSCRIPTION; 1-ALPHA PGC-1-ALPHA; DIABETES-MELLITUS; DOWN-REGULATION; ADIPOSE-TISSUE AB Peroxisome proliferator activator receptor-gamma coactivator 1 (PGC-1) is a major candidate gene for diabetes-related metabolic phenotypes, contributing to decreased expression of nuclear-encoded mitochondrial genes in muscle and adipose tissue. We have demonstrated that muscle expression of PGC-1 alpha and -beta is reduced in both genetic (Lepob/Lepob) and acquired obesity ( high fat diet). In C57BL6 mice, muscle PGC-1 alpha expression decreased by 43% (p < 0.02) after 1 week of a high fat diet and persisted more than 11 weeks. In contrast, PGC-1 alpha reductions were not sustained in obesity-resistant A/J mice. To identify mediators of obesity-linked reductions in PGC-1, we tested the effects of cellular nutrients in C2C12 myotubes. Although overnight exposure to high insulin, glucose, glucosamine, or amino acids had no effect, saturated fatty acids potently reduced PGC-1 alpha and -beta mRNA expression. Palmitate decreased PGC-1 alpha and -beta expression by 38% (p = 0.01) and 53% (p = 0.006); stearate similarly decreased expression of PGC-1 alpha and -beta by 22% (p = 0.02) and 39% (p = 0.02). These effects were mediated at a transcriptional level, as indicated by an 11-fold reduction of PGC-1 alpha promoter activity by palmitate and reversal of effects by histone deacetylase inhibition. Palmitate also ( a) reduced expression of tricarboxylic acid cycle and oxidative phosphorylation mitochondrial genes and (b) reduced oxygen consumption. These effects were reversed by overexpression of PGC-1 alpha or -beta, indicating PGC-1 dependence. Palmitate effects also required p38 MAPK, as demonstrated by 1) palmitate-induced increase in p38 MAPK phosphorylation, 2) reversal of palmitate effects on PGC-1 and mitochondrial gene expression by p38 MAPK inhibitors, and 3) reversal of palmitate effects by small interfering RNA-mediated decreases in p38 alpha MAPK. These data indicate that obesity and saturated fatty acids decrease PGC-1 and mitochondrial gene expression and function via p38 MAPK-dependent transcriptional pathways. C1 Joslin Diabet Ctr, Div Endocrinol, Div Res, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Thyroid Sect, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Patti, ME (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu RI Bianco, Antonio/A-4965-2008; da Silva, Wagner/A-7835-2008 OI Bianco, Antonio/0000-0001-7737-6813; da Silva, Wagner/0000-0002-0001-0386 FU NIDDK NIH HHS [DK060837, DK062948, DK36836, DK65055] NR 74 TC 135 Z9 141 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 2007 VL 282 IS 21 BP 15439 EP 15450 DI 10.1074/jbc.M611214200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 169JX UT WOS:000246589600019 PM 17416903 ER PT J AU Litovchick, L Sadasivam, S Florens, L Zhu, XP Swanson, SK Velmurugan, S Chen, RS Washburn, MP Liu, XS DeCaprio, JA AF Litovchick, Larisa Sadasivam, Subhashini Florens, Laurence Zhu, Xiaopeng Swanson, Selene K. Velmurugan, Soundarapandian Chen, Runsheng Washburn, Michael P. Liu, X. Shirley DeCaprio, James A. TI Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence SO MOLECULAR CELL LA English DT Article ID INDUCED VULVAL DEVELOPMENT; CAENORHABDITIS-ELEGANS; DNA-REPLICATION; C-ELEGANS; DROSOPHILA; IDENTIFICATION; TRANSCRIPTION; INHIBITION; CHROMATIN; DISTINCT AB The mammalian Retinoblastoma (1313) family including pRB, p107, and p130 represses E2F target genes through mechanisms that are not fully understood. In D. melanogaster, RB-dependent repression is mediated in part by the multisubunit protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an integrated approach combining proteomics, genomics, and bioinformatic analyses, we identified a p130 complex termed DIP, RB-like, E2F, and MuvB (DREAM) that contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54, and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in GO and was required for repression of E2F target genes. In S phase, MuvB proteins dissociated from p130 and formed a distinct submodule that bound MYB. This work reveals an evolutionarily conserved multisubunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent genes in quiescence. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Stowers Inst Med Res, Kansas City, MO 64110 USA. Chinese Acad Sci, Inst Biophys, Bioinformat Lab, Beijing 100101, Peoples R China. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu RI Zhu, Xiaopeng/A-6755-2011; OI Zhu, Xiaopeng/0000-0003-2007-9820; Florens, Laurence/0000-0002-9310-6650; Washburn, Michael/0000-0001-7568-2585 FU NCI NIH HHS [P01 CA50661, R01 CA063113]; NHGRI NIH HHS [R01 HG004069, R01 HG004069-01] NR 39 TC 172 Z9 186 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY 25 PY 2007 VL 26 IS 4 BP 539 EP 551 DI 10.1016/j.molcel.2007.04.015 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 174XF UT WOS:000246975500010 PM 17531812 ER PT J AU Matsuoka, S Ballif, BA Smogorzewska, A McDonald, ER Hurov, KE Luo, J Bakalarski, CE Zhao, ZM Solimini, N Lerenthal, Y Shiloh, Y Gygi, SP Elledge, SJ AF Matsuoka, Shuhei Ballif, Bryan A. Smogorzewska, Agata McDonald, E. Robert, III Hurov, Kristen E. Luo, Ji Bakalarski, Corey E. Zhao, Zhenming Solimini, Nicole Lerenthal, Yaniv Shiloh, Yosef Gygi, Steven P. Elledge, Stephen J. TI ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage SO SCIENCE LA English DT Article ID TYROSINE PHOSPHORYLATION; CHECKPOINT; CELLS; IDENTIFICATION; INVOLVEMENT; ACTIVATION; PROTEOMICS; PATHWAYS; CANCER; SITES AB Cellular responses to DNA damage are mediated by a number of protein kinases, including ATM ( ataxia telangiectasia mutated) and ATR ( ATM and Rad3-related). The outlines of the signal transduction portion of this pathway are known, but little is known about the physiological scope of the DNA damage response (DDR). We performed a large-scale proteomic analysis of proteins phosphorylated in response to DNA damage on consensus sites recognized by ATM and ATR and identified more than 900 regulated phosphorylation sites encompassing over 700 proteins. Functional analysis of a subset of this data set indicated that this list is highly enriched for proteins involved in the DDR. This set of proteins is highly interconnected, and we identified a large number of protein modules and networks not previously linked to the DDR. This database paints a much broader landscape for the DDR than was previously appreciated and opens new avenues of investigation into the responses to DNA damage in mammals. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Howard HUghes Med Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Howard HUghes Med Inst, Ctr Genet & Genom, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Taplin Biol Mass Spectrometry Facil, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02214 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Elledge, SJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Howard HUghes Med Inst, Dept Genet, Boston, MA 02115 USA. EM steven_gygi@hms.harvard.edu; selledge@genetics.med.harvard.edu RI Smogorzewska, Agata/B-8891-2011; Bell, Tiffany/F-4403-2010; OI Bakalarski, Corey/0000-0003-1085-7828 FU PHS HHS [1U19A1067751] NR 31 TC 1516 Z9 2046 U1 13 U2 141 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 25 PY 2007 VL 316 IS 5828 BP 1160 EP 1166 DI 10.1126/science.1140321 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 171GQ UT WOS:000246724300034 PM 17525332 ER PT J AU Wang, B Matsuoka, S Ballif, BA Zhang, D Smogorzewska, A Gygi, SP Elledge, SJ AF Wang, Bin Matsuoka, Shuhei Ballif, Bryan A. Zhang, Dong Smogorzewska, Agata Gygi, Steven P. Elledge, Stephen J. TI Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response SO SCIENCE LA English DT Article ID LIGASE ACTIVITY; F-BOX; PHOSPHORYLATION; REPAIR; HETERODIMER; PROTEOMICS; INTERACTS; DOMAINS; BREAKS; CTIP AB The BRCT repeats of the breast and ovarian cancer predisposition protein BRCA1 are essential for tumor suppression. Phosphopeptide affinity proteomic analysis identified a protein, Abraxas, that directly binds the BRCA1 BRCT repeats through a phospho- Ser-X-X-Phe motif. Abraxas binds BRCA1 to the mutual exclusion of BACH1 (BRCA1-associated C-terminal helicase) and CtIP (CtBP-interacting protein), forming a third type of BRCA1 complex. Abraxas recruits the ubiquitin-interacting motif (UIM)-containing protein RAP80 to BRCA1. Both Abraxas and RAP80 were required for DNA damage resistance, G(2)- M checkpoint control, and DNA repair. RAP80 was required for optimal accumulation of BRCA1 on damaged DNA ( foci) in response to ionizing radiation, and the UIM domains alone were capable of foci formation. The RAP80-Abraxas complex may help recruit BRCA1 to DNA damage sites in part through recognition of ubiquitinated proteins. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Howard Hughes Med Inst, Ctr Genet & Genom, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02214 USA. RP Elledge, SJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. EM selledge@genetics.med.harvard.edu RI Smogorzewska, Agata/B-8891-2011 FU Howard Hughes Medical Institute; NCI NIH HHS [1KO1, CA116275-01, K01 CA116275, T32 CA009216, T32CA09216]; PHS HHS [1U19A1067751] NR 29 TC 394 Z9 419 U1 8 U2 43 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 25 PY 2007 VL 316 IS 5828 BP 1194 EP 1198 DI 10.1126/science.1139476 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 171GQ UT WOS:000246724300044 PM 17525340 ER PT J AU Sobhian, B Shao, GZ Lilli, DR Culhane, AC Moreau, LA Xia, B Livingston, DM Greenberg, RA AF Sobhian, Bijan Shao, Genze Lilli, Dana R. Culhane, Aedin C. Moreau, Lisa A. Xia, Bing Livingston, David M. Greenberg, Roger A. TI RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites SO SCIENCE LA English DT Article ID DOUBLE-STRAND BREAKS; HISTONE H2AX; GENOMIC INSTABILITY; REPAIR; PHOSPHORYLATION; PROTEIN; MDC1; MICE; K6 AB Mutations affecting the BRCT domains of the breast cancer-associated tumor suppressor BRCA1 disrupt the recruitment of this protein to DNA double-strand breaks (DSBs). The molecular structures at DSBs recognized by BRCA1 are presently unknown. We report the interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein. RAP80 targets a complex containing the BRCA1-BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating enzyme (DUB) BRCC36 to MDC1-gamma H2AX- dependent lysine(6)- and lysine(63)-linked ubiquitin polymers at DSBs. These events are required for cell cycle checkpoint and repair responses to ionizing radiation, implicating ubiquitin chain recognition and turnover in the BRCA1-mediated repair of DSBs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pathol, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_livingston@dfci.harvard.edu; rogergr@mail.med.upenn.edu FU NCI NIH HHS [K08 CA106597, K08 CA106597-01A2] NR 22 TC 389 Z9 403 U1 1 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 25 PY 2007 VL 316 IS 5828 BP 1198 EP 1202 DI 10.1126/science.1139516 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 171GQ UT WOS:000246724300045 PM 17525341 ER PT J AU Gorry, PR Dunfee, RL Mefford, ME Kunstman, K Morgan, T Moore, JP Mascola, JR Agopian, K Holm, GH Mehle, A Taylor, J Farzan, M Wang, H Ellery, P Willey, SJ Clapham, PR Wolinsky, SM Crowe, SM Gabuzda, D AF Gorry, Paul R. Dunfee, Rebecca L. Mefford, Megan E. Kunstman, Kevin Morgan, Tom Moore, John P. Mascola, John R. Agopian, Kristin Holm, Geoffrey H. Mehle, Andrew Taylor, Joann Farzan, Michael Wang, Hui Ellery, Philip Willey, Samantha J. Clapham, Paul R. Wolinsky, Steven M. Crowe, Suzanne M. Gabuzda, Dana TI Changes in the V3 region of gp 120 contribute to unusually broad coreceptor usage of an HIV-1 isolate from a CCR5 Delta 32 heterozygote SO VIROLOGY LA English DT Article DE HIV-1; CCR5 Delta 32; ENV; V3; CCR5 ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOKINE RECEPTOR D6; HUMAN MONOCLONAL-ANTIBODIES; LONG-TERM SURVIVOR; DISEASE PROGRESSION; GP120 GLYCOPROTEIN; TYPE-1 INFECTION; SMALL-MOLECULE; IN-VIVO; SEROPOSITIVE INDIVIDUALS AB Heterozygosity for the CCR5 Delta 32 allele is associated with delayed progression to AIDS in human immunodeficiency virus type 1 (HIV-1) infection. Here we describe an unusual HIV-1 isolate from the blood of an asymptomatic individual who was heterozygous for the CCR5 Delta 32 allele and had reduced levels of CCR5 expression. The primary virus used CCR5, CXCR4, and an unusually broad range of alternative coreceptors to enter transfected cells. However, only CXCR4 and CCR5 were Used to enter primary T cells and monocyte-derived macrophages, respectively. Full-length Env clones had an unusually long V1/V2 region and rare amino acid variants in the V3 and C4 regions. Mutagenesis studies and structural models suggested that Y308, D321, and to a lesser extent K442 and E444, contribute to the broad coreceptor usage of these Envs, whereas 1317 is likely to be a compensatory change. Furthermore, database analysis suggests that covariation can occur at positions 308/317 and 308/321 in vivo. Y308 and D321 reduced dependence on the extracellular loop 2 (ECL2) region of CCR5, while these residues along with Y330, K442, and E444 enhanced dependence on the CCR5 N-terminus compared to clade B consensus residues at these positions. These results suggest that expanded coreceptor usage of HIV-1 can occur in some individuals without rapid progression to AIDS as a consequence of changes in the V3 region that reduce dependence on the ECL2 region of CCR5 by enhancing interactions with conserved structural elements in G-protein-coupled receptors. (C) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Macfarlane Burnet Inst Med Res & Publ Hlth, Melbourne, Vic, Australia. Monash Univ, Dept Med, Clayton, Vic 3168, Australia. Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Program Mol Med, Worcester, MA 01655 USA. RP Gabuzda, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St JF816, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu RI Holm, Geoffrey/C-3188-2009; Wolinsky, Steven/B-2893-2012 FU NIAID NIH HHS [R21 AI054207, AI41420, R01 AI041420, R01 AI041420-08, R01 AI041420-09, R01 AI041420-10, R21 AI054207-01A1, R21 AI054207-02]; NIMH NIH HHS [MH64408, R01 MH064408, R01 MH064408-02, R01 MH064408-03, R01 MH064408-04]; NIMHD NIH HHS [L60 MD003100]; NINDS NIH HHS [NS37277, R01 NS037277, R01 NS037277-05A1, R01 NS037277-06, R01 NS037277-07, R01 NS037277-08, R01 NS037277-09] NR 76 TC 29 Z9 29 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 25 PY 2007 VL 362 IS 1 BP 163 EP 178 DI 10.1016/j.virol.2006.11.025 PG 16 WC Virology SC Virology GA 168ZU UT WOS:000246563300018 PM 17239419 ER PT J AU Greene, MF AF Greene, Michael F. TI The intimidation of American physicians - Banning partial-birth abortion SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greene, MF (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 24 PY 2007 VL 356 IS 21 BP 2128 EP 2129 DI 10.1056/NEJMp078084 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 170ON UT WOS:000246673100002 PM 17452436 ER PT J AU Chan, AT Ogino, S Fuchs, CS AF Chan, Andrew T. Ogino, Shuji Fuchs, Charles S. TI Aspirin and the risk of colorectal cancer in relation to the expression of COX-2 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYCLOOXYGENASE-2 GENE-EXPRESSION; FOOD FREQUENCY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; CORONARY-HEART-DISEASE; RANDOMIZED-TRIAL; ADENOMA RECURRENCE; COMPETING RISKS; UP-REGULATION; PREVENTION AB Background: Regular use of aspirin reduces the risk of a colorectal neoplasm, but the mechanism by which aspirin affects carcinogenesis in the colon is not well understood. Methods: We estimated cyclooxygenase-2 (COX-2) expression by immunohistochemical assay of sections from paraffin-embedded colorectal-cancer specimens from two large cohorts of participants who provided data on aspirin use from a questionnaire every 2 years. We applied Cox regression to a competing-risks analysis to compare the effects of aspirin use on the relative risk of colorectal cancer in relation to the expression of COX-2 in the tumor. Results: During 2,446,431 person-years of follow-up of 82,911 women and 47,363 men, we found 636 incident colorectal cancers that were accessible for determination of COX-2 expression. Of the tumors, 423 (67%) had moderate or strong COX-2 expression. The effect of aspirin use differed significantly in relation to COX-2 expression (P for heterogeneity=0.02). Regular aspirin use conferred a significant reduction in the risk of colorectal cancers that overexpressed COX-2 (multivariate relative risk, 0.64; 95% confidence interval [CI], 0.52 to 0.78), whereas regular aspirin use had no influence on tumors with weak or absent expression of COX-2 (multivariate relative risk, 0.96; 95% CI, 0.73 to 1.26). The age-standardized incidence rate for cancers that overexpressed COX-2 was 37 per 100,000 person-years among regular aspirin users, as compared with 56 per 100,000 person-years among those who did not use aspirin regularly; in contrast, the rate for cancers with weak or absent COX-2 expression was 27 per 100,000 person-years among regular aspirin users, as compared with 28 per 100,000 person-years among nonregular aspirin users. Conclusions: Regular use of aspirin appears to reduce the risk of colorectal cancers that overexpress COX-2 but not the risk of colorectal cancers with weak or absent expression of COX-2. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 728A, Boston, MA 02114 USA. EM achan@partners.org RI Chan, Andrew/D-3361-2013 FU NCI NIH HHS [CA10741, CA55075, CA87969] NR 42 TC 360 Z9 378 U1 5 U2 39 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 24 PY 2007 VL 356 IS 21 BP 2131 EP 2142 DI 10.1056/NEJMoa067208 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 170ON UT WOS:000246673100003 PM 17522398 ER PT J AU Shepard, JAO Wright, CD Hasserjian, RP Fidias, P Choi, NCH AF Shepard, Jo-Anne O. Wright, Cameron D. Hasserjian, Robert P. Fidias, Panos Choi, Noah C. H. TI Case 16-2007: A 61-year-old man with a mediastinal mass - Thymoma, WHO type B1, with individual changes after preoperative chemoradiation. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STAGE-III THYMOMA; THYMIC EPITHELIAL TUMORS; RADIATION-THERAPY; MALIGNANT THYMOMA; SURGICAL RESECTION; INVASIVE THYMOMA; MULTIDISCIPLINARY APPROACH; ADJUVANT RADIATION; INTERGROUP TRIAL; LUNG-CANCER C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Shepard, JAO (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 40 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 24 PY 2007 VL 356 IS 21 BP 2185 EP 2193 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 170ON UT WOS:000246673100011 PM 17522403 ER PT J AU Fan, BJ Ko, WC Wang, DY Canlas, O Ritch, R Lam, DSC Pang, CP AF Fan, Bao Jian Ko, Wendy Charles Wang, Dan Yi Canlas, Oscar Ritch, Robert Lam, Dennis S. C. Pang, Chi Pui TI Fine mapping of new glaucoma locus GLC1M and exclusion of neuregulin 2 as the causative gene SO MOLECULAR VISION LA English DT Article ID OPEN-ANGLE GLAUCOMA; WIDE SCAN MAPS; TENSION GLAUCOMA; WDR36 GENE; OPTINEURIN; MUTATIONS; JUVENILE; ADULT; MYOCILIN; PREVALENCE AB PURPOSE: We recently identified a novel glaucoma locus on 5q22.1-q32, designated as GLC1M, in a family from the Philippines with autosomal dominant juvenile-onset primary open angle glaucoma (JOAG). No mutations in myocilin (MYOC), optineurin (OPTN), and WD-repeat protein 36 (WDR36) were found. Neuregulin 2 (NRG2) is an excellent potential functional as well as positional candidate at GLC1M. The goal of the present study was to evaluate the role of the NRG2 gene in this JOAG family and unrelated JOAG patients and to refine the critical interval for GLC1M. METHODS: Genomic DNA was obtained from 27 family members. All coding exons and splicing sites of NRG2 were screened for sequence alterations by polymerase chain reaction (PCR) and DNA sequencing. A cohort of 92 unrelated JOAG patients and 92 control subjects were genotyped for the three single nucleotide polymorphisms (SNPs) of NRG2 by PCR and DNA sequencing. Haplotype and segregation analyses were performed in the family. Fisher's exact test was used to compare the frequencies of the NRG2 polymorphisms between affected and unaffected subjects in the family and between unrelated JOAG patients and control subjects. RESULTS: Three SNPs were identified: c.98G>A (S33N), IVS3+13A>G (rs889022), and c.1976A>G (G659G). None of them segregated with the JOAG phenotype in this family. No association was found between NRG2 and JOAG in the case-control study (p>0.12). However, further inspection of the haplotypes in the family localized the NRG2 gene telomeric to the disease locus. The critical interval of GLC1M was therefore refined to a region of 28 Mb between D5S2051 and NRG2. CONCLUSIONS: The linkage interval for GLC1M was refined to a smaller region. The NRG2 gene was excluded as the causative gene for JOAG. C1 Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Peoples R China. Jose B Lingad Mem Reg Hosp, San Fernando, Philippines. New York Eye & Ear Infirmary, Dept Ophthalmol, New York, NY USA. New York Med Coll, Valhalla, NY USA. RP Fan, BJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM baojian_fan@meei.harvard.edu RI Pang, Chi/I-5388-2014; OI Fan, Baojian/0000-0002-6851-2737 NR 33 TC 15 Z9 19 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD MAY 23 PY 2007 VL 13 IS 80-85 BP 779 EP 784 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 177HR UT WOS:000247144700006 PM 17563728 ER PT J AU Smith, MD Rosenow, MA Wang, MT Allen, JP Szostak, JW Chaput, JC AF Smith, Matthew D. Rosenow, Matthew A. Wang, Meitian Allen, James P. Szostak, Jack W. Chaput, John C. TI Structural Insights into the Evolution of a Non-Biological Protein: Importance of Surface Residues in Protein Fold Optimization SO PLOS ONE LA English DT Article AB Phylogenetic profiling of amino acid substitution patterns in proteins has led many to conclude that most structural information is carried by interior core residues that are solvent inaccessible. This conclusion is based on the observation that buried residues generally tolerate only conserved sequence changes, while surface residues allow more diverse chemical substitutions. This notion is now changing as it has become apparent that both core and surface residues play important roles in protein folding and stability. Unfortunately, the ability to identify specific mutations that will lead to enhanced stability remains a challenging problem. Here we discuss two mutations that emerged from an in vitro selection experiment designed to improve the folding stability of a non-biological ATP binding protein. These mutations alter two solvent accessible residues, and dramatically enhance the expression, solubility, thermal stability, and ligand binding affinity of the protein. The significance of both mutations was investigated individually and together, and the X-ray crystal structures of the parent sequence and double mutant protein were solved to a resolution limit of 2.8 and 1.65 angstrom, respectively. Comparative structural analysis of the evolved protein to proteins found in nature reveals that our non-biological protein evolved certain structural features shared by many thermophilic proteins. This experimental result suggests that protein fold optimization by in vitro selection offers a viable approach to generating stable variants of many naturally occurring proteins whose structures and functions are otherwise difficult to study. C1 [Smith, Matthew D.; Rosenow, Matthew A.; Chaput, John C.] Arizona State Univ, Ctr BioOpt Nanotechnol, Biodesign Inst, Tempe, AZ 85287 USA. [Smith, Matthew D.; Rosenow, Matthew A.; Wang, Meitian; Allen, James P.; Chaput, John C.] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Chaput, JC (reprint author), Arizona State Univ, Ctr BioOpt Nanotechnol, Biodesign Inst, Tempe, AZ 85287 USA. EM john.chaput@asu.edu RI Wang, Meitian/D-3208-2013 FU Biodesign Institute; NIH; NASA Astrobiology Institute FX This work was supported by new laboratory start-up funds from the The Biodesign Institute to JCC and grants from the NIH and NASA Astrobiology Institute to JWS. JWS is an Investigator, and J.C.C. was a Research Associate of the Howard Hughes Medical Institute. NR 47 TC 11 Z9 11 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 23 PY 2007 VL 2 IS 5 AR e467 DI 10.1371/journal.pone.0000467 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DZ UT WOS:000207446000015 PM 17520026 ER PT J AU Morrow, DA AF Morrow, David A. TI Appraisal of Myeloperoxidase for evaluation of patients with suspected acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID NITRIC-OXIDE C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Cardiovasc,TIMI Study Grp, Boston, MA 02115 USA. RP Morrow, DA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Cardiovasc,TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM dmorrow@partners.org NR 12 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 22 PY 2007 VL 49 IS 20 BP 2001 EP 2002 DI 10.1016/j.jacc.2007.03.010 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 171KF UT WOS:000246734100002 PM 17512354 ER PT J AU Kinlay, S AF Kinlay, Scott TI Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein - A meta-analysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; SCANDINAVIAN SIMVASTATIN SURVIVAL; RANDOMIZED CONTROLLED-TRIAL; INCREASES COLLAGEN CONTENT; TYPE-2 DIABETES-MELLITUS; PLACEBO-CONTROLLED TRIAL; COA REDUCTASE INHIBITOR; STABLE ANGINA-PECTORIS; PRIMARY HYPERCHOLESTEROLEMIA; ENDOTHELIAL FUNCTION AB Objectives This study sought to assess the contribution of low-density lipoprotein (LDL)-dependent and LDL-independent effects of LDL-lowering therapies to changes in C-reactive protein (CRP) in healthy or stable subjects. Background Correlations of change in LDL and CRP in individuals are lowered by their measurement variability. By using average changes in LDL and CRP in study groups, meta-analysis reduces this variability to better assess their correlation. Methods A systematic search for randomized place bo-control led trials reporting change in LDL and CRP with LDL-lowering interventions retrieved 23 studies with 57 groups treated with a variety of statins, nonstatin drugs, or other regimens. Meta-analysis techniques assessed the relationships between average mean differences (placebo - treatment) in change in CRP and LDL. Results The overall reduction in CRP was 28% (95% confidence interval 26% to 30%). Significantly greater CRP reduction occurred in statin and statin-ezetimibe interventions, interventions using 80 mg/day of statins, and with greater LDL lowering. Meta-regression analysis showed a strong correlation between the change in LDL and CRP (r = 0.80, p < 0.001). Statin therapies had no significant effect on CRP after adjusting for the change in LDL. In a multivariate model applied to a range of LDL reduction typically seen with statins (20% to 60%), 89% to 98% of CRP change was related to LDL lowering and 2% to 11% was related to non-LDL effects of statins. Conclusions In clinical practice, most of the anti-inflammatory effect of LDL-lowering therapies is related to the magnitude of change in LDL. The potential non-LDL effects of statins on inflammation are much smaller in magnitude. C1 VA Boston Healthcare Syst, Div Cardiovasc, Boston, MA 02132 USA. Brigham & Womens Hosp, Boston, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA 02132 USA. RP Kinlay, S (reprint author), VA Boston Healthcare Syst, Div Cardiovasc, 1400 VFW Pkwy, Boston, MA 02132 USA. EM skinlay@partners.org NR 70 TC 112 Z9 119 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAY 22 PY 2007 VL 49 IS 20 BP 2003 EP 2009 DI 10.1016/j.jacc.2007.01.083 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 171KF UT WOS:000246734100003 PM 17512355 ER PT J AU Wen, PY DeAngelis, LM AF Wen, Patrick Y. DeAngelis, Lisa M. TI Chemotherapy for low-grade gliomas - Emerging consensus on its benefits SO NEUROLOGY LA English DT Editorial Material ID PHASE-II TRIAL; ANAPLASTIC OLIGODENDROGLIOMAS; TEMOZOLOMIDE; OLIGOASTROCYTOMAS; PROCARBAZINE; VINCRISTINE; EXPRESSION; LOMUSTINE; DELETIONS; SURVIVAL C1 Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, 75 Francis St, Boston, MA 02115 USA. EM pwen@partners.org NR 15 TC 15 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 22 PY 2007 VL 68 IS 21 BP 1762 EP 1763 DI 10.1212/01.wnl.0000266866.13748.a9 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 170LI UT WOS:000246664500002 PM 17515537 ER PT J AU Lyketsos, CG AF Lyketsos, C. G. CA ADAPT Res Grp TI Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial SO NEUROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; REPLACEMENT THERAPY; CACHE COUNTY; DOUBLE-BLIND; DEMENTIA; MEMORY; ROFECOXIB; PLACEBO AB Objective: To evaluate the efficacy and safety of naproxen and celecoxib for the primary prevention of Alzheimer disease ( AD). Methods: Randomized, placebo-controlled, double-masked clinical trial conducted at six US dementia research clinics. Volunteers aged 70+ years, with cognitive screening scores above designated cut-offs and a family history of AD, were randomly assigned to celecoxib 200 mg BID, naproxen sodium 220 mg BID, or placebo. Enrollment began in early 2001. The main outcome measure was diagnosis of AD after randomization. Results: On December 17, 2004, treatments were suspended. Events while on treatment yielded hazard ratios vs placebo of 1.99 (95% CI 0.80 to 4.97; p = 0.14) for celecoxib and 2.35 (0.95 to 5.77; p = 0.06) for naproxen. Imperfect screening measures led to enrollment of 7 individuals with dementia and 46 others with milder cognitive syndromes. Their (prevalent) illness was detected at enrollment and diagnosed within 6 months following randomization. Secondary analyses that excluded the 7 cases of prevalent dementia showed increased hazard ratios for AD with both treatments. Neither treatment produced a notable effect on the incidence of milder cognitive syndromes. Conclusions: These results do not support the hypothesis that celecoxib or naproxen prevent Alzheimer dementia, at least within the early years after initiation of treatment. Masked long-term follow-up of these participants will be essential. C1 Johns Hopkins Bayview, Dept Psychiat, Baltimore, MD 21224 USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Sun Hlth Res Inst, Sun City, AZ USA. RP Lyketsos, CG (reprint author), Johns Hopkins Bayview, Dept Psychiat, 5300 Alpha Commons Dr,4th Floor, Baltimore, MD 21224 USA. NR 40 TC 140 Z9 142 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAY 22 PY 2007 VL 68 IS 21 BP 1800 EP 1808 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 170LI UT WOS:000246664500007 ER PT J AU Goh, KI Cusick, ME Valle, D Childs, B Vidal, M Barabasi, AL AF Goh, Kwang-Il Cusick, Michael E. Valle, David Childs, Barton Vidal, Marc Barabasi, Albert-Laszlo TI The human disease network SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biological networks; complex networks; human genetics; systems biology; diseasome ID PROTEIN INTERACTION NETWORK; TOPOLOGICAL FEATURES; BIOLOGY; GENES; INTERACTOME; DISORDERS; ORGANIZATION; MODULARITY; GENOMICS; YEAST AB A network of disorders and disease genes linked by known disorder-gene associations offers a platform to explore in a single graph-theoretic framework all known phenotype and disease gene associations, indicating the common genetic origin of many diseases. Genes associated with similar disorders show both higher likelihood of physical interactions between their products and higher expression profiling similarity for their transcripts, supporting the existence of distinct disease-specific functional modules. We find that essential human genes are likely to encode hub proteins and are expressed widely in most tissues. This suggests that disease genes also would play a central role in the human interactome. In contrast, we find that the vast majority of disease genes are nonessential and show no tendency to encode hub proteins, and their expression pattern indicates that they are localized in the functional periphery of the network. A selection-based model explains the observed difference between essential and disease genes and also suggests that diseases caused by somatic mutations should not be peripheral, a prediction we confirm for cancer genes. C1 Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Korea Univ, Dept Phys, Seoul 136713, South Korea. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. RP Vidal, M (reprint author), Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. EM marc_vidal@dfci.harvard.edu; alb@nd.edu FU NCI NIH HHS [U56 CA113004]; PHS HHS [IH U01 A1070499-01] NR 30 TC 1293 Z9 1348 U1 17 U2 152 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2007 VL 104 IS 21 BP 8685 EP 8690 DI 10.1073/pnas.0701361104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 173DM UT WOS:000246853700004 PM 17502601 ER PT J AU Okada, T Liew, CW Hu, J Hinault, C Michael, MD Krutzfeldt, J Yin, C Holzenberger, M Stoffel, M Kulkarni, RN AF Okada, Terumasa Liew, Chong Wee Hu, Jiang Hinault, Charlotte Michael, M. Dodson Krutzfeldt, Jan Yin, Catherine Holzenberger, Martin Stoffel, Markus Kulkarni, Rohit N. TI Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta-cell growth; compensatory hyperplasia; beta-cell apoptosis ID GENE-EXPRESSION; GLUCOSE-INTOLERANCE; PANCREATIC-ISLETS; RAT PANCREAS; MASS; DIFFERENTIATION; HYPERPLASIA; METABOLISM; SECRETION; KNOCKOUT AB Insulin and insulin-like growth factor 1 (IGF1) are ubiquitous growth factors that regulate proliferation in most mammalian tissues including pancreatic islets. To explore the specificity of insulin receptors in compensatory beta-cell growth, we examined two models of insulin resistance. In the first model, we used liver-specific insulin receptor knockout (LIRKO) mice, which exhibit hyperinsulinemia without developing diabetes due to a compensatory increase in beta-cell mass. LIRKO mice, also lacking functional insulin receptors in P-cells (beta IRKO/LIRKO), exhibited severe glucose intolerance but failed to develop compensatory islet hyperplasia, together leading to early death. In the second model, we examined the relative significance of insulin versus IGF1 receptors in islet growth by feeding high-fat diets to beta IRKO and beta-cell-specific IGF1 receptor knockout (beta IGFRKO) mice. Although both groups on the high-fat diet developed insulin resistance, beta IRKO, but not beta IGFRKO, mice exhibited poor islet growth consistent with insulin-stimulated phosphorylation, nuclear exclusion of FoxC11, and reduced expression of Pdx-1. Together these data provide direct genetic evidence that insulin/FoxO1/Pdx-1 signaling is one pathway that is crucial for islet compensatory growth response to insulin resistance. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Rockefeller Univ, Lab Metab Dis, New York, NY 10021 USA. Hop St Antoine, INSERM, U515, Paris 12, France. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu OI hinault, charlotte/0000-0002-3588-039X FU NIDDK NIH HHS [P30 DK036836, P01 DK042502, P30 DK36836, R01 DK055033, R01 DK067536, R01 DK068721, R01 DK55033, R01 DK67536, R01 DK68721, U10DK42502, U19 DK042502] NR 42 TC 159 Z9 166 U1 2 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2007 VL 104 IS 21 BP 8977 EP 8982 DI 10.1073/pnas.0608703104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 173DM UT WOS:000246853700054 PM 17416680 ER PT J AU Baker, CI Liu, J Wald, LL Kwong, KK Benner, T Kanwisher, N AF Baker, Chris I. Liu, Jia Wald, Lawrence L. Kwong, Kenneth K. Benner, Thomas Kanwisher, Nancy TI Visual word processing and experiential origins of functional selectivity in human extrastriate cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE learning; vision; fMRI; experience; ventral visual pathway ID LETTER-STRING PERCEPTION; SURFACE-BASED ANALYSIS; LEFT FUSIFORM GYRUS; FORM AREA; INFEROTEMPORAL CORTEX; LETTER RECOGNITION; ADULT MONKEYS; FACE AREA; OBJECT; DYSLEXIA AB How do category-selective regions arise in human extrastriate cortex? Visually presented words provide an ideal test of the role of experience: Although individuals have extensive experience with visual words, our species has only been reading for a few thousand years, a period not thought to belong enough for natural selection to produce a genetically specified mechanism dedicated to visual word recognition per se. Using relatively high-resolution functional magnetic resonance imaging (1.4 x 1.4 x 2-mm voxels), we identified a small region of extrastriate cortex in most participants that responds selectively to both visually presented words and consonant strings, compared with line drawings, digit strings, and Chinese characters. Critically, we show that this pattern of selectivity is dependent on experience with specific orthographies: The same region responds more strongly to Hebrew words in Hebrew readers than in nonreaders of Hebrew. These results indicate that extensive experience with a given visual category can produce strong selectivity for that category in discrete cortical regions. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, MIT, Sch Med,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Baker, CI (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Room 4C104, Bethesda, MD 20892 USA. EM bakerchris@mail.nih.gov; ngk@mit.edu RI Liu, Jia/C-5630-2011; Wald, Lawrence/D-4151-2009; OI Baker, Chris/0000-0001-6861-8964 FU NCRR NIH HHS [P41 RR014075, P41-RR14075]; NEI NIH HHS [EY13455, R01 EY013455]; NINDS NIH HHS [NS049052] NR 58 TC 174 Z9 181 U1 1 U2 28 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2007 VL 104 IS 21 BP 9087 EP 9092 DI 10.1073/pnas.0703300104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 173DM UT WOS:000246853700073 PM 17502592 ER PT J AU Unkelbach, J Chan, TCY Bortfeld, T AF Unkelbach, Jan Chan, Timothy C. Y. Bortfeld, Thomas TI Accounting for range uncertainties in the optimization of intensity modulated proton therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIATION-THERAPY; ORGAN MOVEMENTS; BEAM PROFILES; RADIOTHERAPY AB Treatment plans optimized for intensity modulated proton therapy (IMPT) may be sensitive to range variations. The dose distribution may deteriorate substantially when the actual range of a pencil beam does not match the assumed range. We present two treatment planning concepts for IMPT which incorporate range uncertainties into the optimization. The first method is a probabilistic approach. The range of a pencil beam is assumed to be a random variable, which makes the delivered dose and the value of the objective function a random variable too. We then propose to optimize the expectation value of the objective function. The second approach is a robust formulation that applies methods developed in the field of robust linear programming. This approach optimizes the worst case dose distribution that may occur, assuming that the ranges of the pencil beams may vary within some interval. Both methods yield treatment plans that are considerably less sensitive to range variations compared to conventional treatment plans optimized without accounting for range uncertainties. In addition, both approaches-although conceptually different-yield very similar results on a qualitative level. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Ctr Operat Res, Cambridge, MA 02139 USA. RP Unkelbach, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM junkelback@partners.org; tcychan@mit.edu; tbortfeld@partners.org FU NCI NIH HHS [P01-CA21239, R01 CA103904] NR 13 TC 88 Z9 88 U1 0 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAY 21 PY 2007 VL 52 IS 10 BP 2755 EP 2773 DI 10.1088/0031-9155/52/10/009 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 163QL UT WOS:000246177000009 PM 17473350 ER PT J AU Jordan, VC Gelber, RD AF Jordan, V. Craig Gelber, Richard D. TI Problems with the progesterone receptor in practice? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID EARLY BREAST-CANCER; EPIDERMAL GROWTH-FACTOR; ESTROGEN-RECEPTOR; ENDOCRINE THERAPY; POSTMENOPAUSAL WOMEN; PREDICTING RESPONSE; RANDOMIZED-TRIALS; MCF-7 CELLS; ATAC TRIAL; TAMOXIFEN C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jordan, VC (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. RI Jordan, V. Craig/H-4491-2011 FU NCI NIH HHS [P30 CA006927, CA 89018]; NIGMS NIH HHS [R01 GM067156] NR 25 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2007 VL 25 IS 15 BP 1957 EP 1959 DI 10.1200/JCO.2007.10.7342 PG 3 WC Oncology SC Oncology GA 172KW UT WOS:000246804200004 PM 17452674 ER PT J AU Goss, PE Ingle, JN Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, M Tu, DH Shepherd, LE Pritchard, KI Livingston, RB Davidson, NE Norton, L Perez, EA Abrams, JS Cameron, DA Palmer, MJ Pater, JL AF Goss, Paul E. Ingle, James N. Martino, Silvana Robert, Nicholas J. Muss, Hyman B. Piccart, Martine J. Castiglione, Monica Tu, Dongsheng Shepherd, Lois E. Pritchard, Kathleen I. Livingston, Robert B. Davidson, Nancy E. Norton, Larry Perez, Edith A. Abrams, Jeffrey S. Cameron, David A. Palmer, Michael J. Pater, Joseph L. TI Efficacy of letrozole extended adjuvant therapy according to estrogen receptor and progesterone receptor status of the primary tumor: National Cancer Institute of Canada Clinical Trials Group MA.17 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 28th Annual San Antonio Breast Cancer Symposium CY DEC 08-11, 2005 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy & Res Ctr, Univ Texas San Antonio, Hlth Sci Ctr ID EARLY BREAST-CANCER; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; ENDOCRINE THERAPY; TAMOXIFEN THERAPY; UPDATED FINDINGS; PHASE-III; ANASTROZOLE; MULTICENTER; COMBINATION AB Purpose Controversy exists regarding estrogen (ER) and progesterone (PgR) receptor expression on efficacy of adjuvant endocrine therapy. In the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, the benefit of anastrozole over tamoxifen was substantially greater in ER+/PgR- than ER+/PgR+ tumors. In BIG 1-98 (Breast International Group), the benefits of letrozole over tamoxifen were the same in ER+ tumors irrespective of PgR. MA.17 randomized postmenopausal women after 5 years of tamoxifen, to letrozole or placebo. We present outcomes according to tumor receptor status. Patients and Methods Disease-free survival (DFS) and other outcomes were assessed in subgroups by ER and PgR status using Cox's proportional hazards model, adjusting for nodal status and prior adjuvant chemotherapy. Results The DFS hazard ratio (HB) for letrozole versus placebo in ER+/PgR+ tumors (N = 3,809) was 0.49 (95% Cl, 0.36 to 0.67) versus 1.21 (95% Cl, 0.63 to 2.34) in ER+/PgR- tumors (n = 636). ER+/PgR+ letrozole patients experienced significant benefit in distant DFS (DDFS; HR = 0.53, 95% Cl, 0.35 to 0.80) and overall survival (OS, HR = 0.58; 95% Cl, 0.37 to 0.90). A statistically significant difference in treatment effect between EB+/PgR+ and ER+/PgR- subgroups for DFS was observed (P =.02), but not for DDFS (P =.06) or CS (P =.09). Conclusion These results suggest greater benefit for letrozole in DFS DDFS and OS in patients with,, ER+/PgR+ tumors, implying greater activity of letrozole in tumors with a functional ER. However, because this is a subset analysis and receptors were not measured centrally we caution against, using these results for clinical decision making. C1 Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. John Wayne Canc Inst, Santa Monica, CA USA. Inova Fairfax Hosp, Falls Church, VA USA. Univ Vermont, Burlington, VT USA. Inst Jules Bordet, B-1000 Brussels, Belgium. SIBCSG Coordinating Ctr, Bern, Switzerland. Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. Univ Toronto, Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Univ Washington, Seattle, WA 98195 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NCI, Clin Invest Branch, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Jacksonville, FL 32224 USA. Western Gen Hosp, Edinburgh Breast Unit, Edinburgh EH4 2XU, Midlothian, Scotland. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, 55 Fruit St,Lawrence House,LRH-302, Boston, MA 02114 USA. EM pgoss@partners.org OI Norton, Larry/0000-0003-3701-9250 NR 25 TC 79 Z9 81 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2007 VL 25 IS 15 BP 2006 EP 2011 DI 10.1200/JCO.2006.09.4482 PG 6 WC Oncology SC Oncology GA 172KW UT WOS:000246804200012 PM 17452676 ER PT J AU Karlsson, P Cole, BF Price, KN Coates, AS Castiglione-Gertsch, M Gusterson, BA Murray, E Linditner, J Collins, JP Holmberg, SB Fey, MF Thurliumann, B Crivellari, D Forbes, JF Gelber, RD Goldhirsch, A Wallgren, A AF Karlsson, Per Cole, Bernard F. Price, Karen N. Coates, Alan S. Castiglione-Gertsch, Monica Gusterson, Barry A. Murray, Elizabeth Linditner, Jurij Collins, John P. Holmberg, Stig B. Fey, Martin F. Thuerliumann, Beat Crivellari, Diana Forbes, John F. Gelber, Richard D. Goldhirsch, Aron Wallgren, Arne TI The role of the number of uninvolved lymph nodes in predicting locoregional recurrence in breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 5th European Breast Cancer Conference CY MAR 21-25, 2006 CL Nice, FRANCE ID LOCO-REGIONAL RECURRENCE; GROUP TRIALS I; ADJUVANT CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; CLINICAL-TRIALS; POSTOPERATIVE RADIOTHERAPY; RANDOMIZED-TRIALS; RISK-FACTORS; SURVIVAL; MASTECTOMY AB Purpose To identify groups of early breast cancer patients with substantial risk (10-year risk > 20%) for locoregional failure (LRF) who might benefit from postmastectomy radiotherapy (RT). Patients and Methods Prognostic factors for LRF were evaluated among 6,660 patients (2,588 node-negative patients, 4,072 node-positive patients) in International Breast Cancer Study Group Trials I to IX treated with chemotherapy and/or endocrine therapy, and observed for a median of 14 years. In total, 1,251 LRFs were detected. All patients were treated with mastectomy without RT. Results No group with 10-year LRF risk exceeding 20% was found among patients with node-negative disease. Among patients with node-positive breast cancer, increasing numbers of uninvolved nodes were significantly associated with decreased risk of LBF, even after adjustment for other prognostic factors. The highest quartile of uninvolved nodes was compared with the lowest quartile. Among premenopausal patients, LRF risk was decreased by 35% (P =.0010); among postmenopausal patients, LRF risk was decreased by 46% (P <.0001). The 10-year cumulative incidence of LRF was 20% among patients with one to three involved lymph nodes and fewer than 10 uninvolved nodes. Age younger than 40 years and vessel invasion were also associated significantly with increased risk. Among patients with node-positive disease, overall survival was significantly greater in those with higher numbers of uninvolved nodes examined (P <.0001). Conclusion Patients with one to three involved nodes and a low number of uninvolved nodes, vessel invasion, or young age have an increased risk of LRF and may be candidates for a similar treatment as those with at least four lymph node metastases. C1 Gothenburg Univ, Sahlgrenska Univ Hosp, Dept Oncol, S-41345 Gothenburg, Sweden. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, IBCSG,Stat Ctr, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Dartmouth Coll Sch Med, Lebanon, NH USA. Inselspital Bern, CH-3010 Bern, Switzerland. IBCSG, Bern, Switzerland. Kantonsspital, Senol Ctr Eastern Switzerland, St Gallen, Switzerland. Oncol Inst So Switzerland, Bellinzona, Switzerland. Swiss Grp Clin Canc Res, Bern, Switzerland. Univ Sydney, Sydney, NSW 2006, Australia. Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. Univ Newcastle, Newcastle Mater Hosp, Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW 2308, Australia. Univ Glasgow, Western Infirm, Div Canc Sci & Mol Pathol, Glasgow G11 6NT, Lanark, Scotland. Groote Shuur Hosp, Cape Town, South Africa. Univ Cape Town, ZA-7925 Cape Town, South Africa. Inst Oncol, Ljubljana, Slovenia. Ctr Riferimento Oncol, I-33081 Aviano, Italy. European Inst Oncol, Milan, Italy. RP Karlsson, P (reprint author), Gothenburg Univ, Sahlgrenska Univ Hosp, Dept Oncol, S-41345 Gothenburg, Sweden. EM per.karlsson@oncology.gu.se RI gusterson, barry/D-3752-2009 FU NCI NIH HHS [CA-75362] NR 34 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2007 VL 25 IS 15 BP 2019 EP 2026 DI 10.1200/JCO.2006.09.8152 PG 8 WC Oncology SC Oncology GA 172KW UT WOS:000246804200014 PM 17420511 ER PT J AU Schwartz, CL Garlick, R Teot, L Krailo, M Chen, ZJ Goorin, A Grier, HE Bernstein, ML Meyers, P AF Schwartz, Cindy L. Garlick, Richard Teot, Lisa Krailo, Mark Chen, Zhengjia Goorin, Allen Grier, Holcombe E. Bernstein, Mark L. Meyers, Paul TI Multiple drug resistance in osteogenic sarcoma: INT0133 from the Children's Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE METHOTREXATE; P-GLYCOPROTEIN; NONMETASTATIC OSTEOSARCOMA; PREOPERATIVE CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; EXPRESSION; EXTREMITIES; DOXORUBICIN; TRIAL; TUMOR AB Purpose Multiple drug resistance due to P-glycoprotein (P-gp) expression has been reported to be a cause of disease recurrence in osteosarcoma. Tumor specimens derived from children and young adults with osteosarcoma enrolled onto a national Intergroup trial (INT0133) were analyzed prospectively to determine the role of multiple drug resistance in osteosarcoma. Patients and Methods From October 15, 1992, to November 25, 1997, 685 patients with localized, high-grade osteosarcoma were enrolled onto INT0133. Paraffin-embedded diagnostic tumor specimens were assayed for P-gp using monoclonal antibodies C-494 (139 patients) and JSB-1 (133 patients). Percent necrosis at the time of definitive surgery (NEC), event-free survival (EFS), and overall survival (OS) were evaluated as outcome measures for patients with P-gp-positive disease and were compared with patients with P-gp-negative disease. Results P-gp expression in the biopsy specimen did not significantly increase the risk for adverse outcomes as measured by EFS, OS, or NEC. EFS for those patients with C-494-positive tumors was 59% at 4 years versus 61% at 4 years for patients with C-494-negative tumors (P =.79), or 58% at 4 years versus 61% at 4 years for patients with JSB-1 -positive versus JSB-1-negative tumors (P =.65). OS for patients with C-494-positive tumors was 82% at 4 years versus 82% at 4 years for patients with C-494-negative tumors (P =.61). Conclusion Prospective analysis of the role of multiple drug resistance in localized osteosarcoma did not find that immunohistochemical analysis of P-gp expression predicted outcome for patients treated on INT0133. C1 Hasbro Childrens Hosp, Brown Med Sch, Providence, RI 02903 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Childrens Oncol Grp Operat Ctr, Arcadia, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. RP Schwartz, CL (reprint author), Hasbro Childrens Hosp, Brown Med Sch, 593 Eddy St MP117, Providence, RI 02903 USA. EM cschwartz1@lifespan.org OI Meyers, Paul/0000-0001-6146-6101 FU NCI NIH HHS [CA 13539, CA 30969, U10 CA 98543] NR 24 TC 53 Z9 57 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2007 VL 25 IS 15 BP 2057 EP 2062 DI 10.1200/JCO.2006.07.7776 PG 6 WC Oncology SC Oncology GA 172KW UT WOS:000246804200019 PM 17513810 ER PT J AU Mitchell, MS Abrams, J Thompson, JA Kashani-Sabet, M DeConti, RC Hwu, WJ Atkins, MB Whitman, E Ernstoff, MS Haluska, FG Jakowatz, JG Das Gupta, TK Richards, JM Samlowski, WE Costanzi, JJ Aronson, FR Deisseroth, AB Dudek, AZ Jones, VE AF Mitchell, Malcolm S. Abrams, Judith Thompson, John A. Kashani-Sabet, Mohammed DeConti, Ronald C. Hwu, Wen-Jen Atkins, Michael B. Whitman, Eric Ernstoff, Marc S. Haluska, Frank G. Jakowatz, James G. Das Gupta, Tapas K. Richards, Jon M. Samlowski, Wolfram E. Costanzi, John J. Aronson, Frederick R. Deisseroth, Albert B. Dudek, Arkadiusz Z. Jones, Vicky E. TI Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon alfa-2b compared with high-dose interferon alfa-2b for resected stage III cutaneous melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 19-23, 2000 CL NEW ORLEANS, LA SP Amer Soc Clin Oncol ID HIGH-RISK MELANOMA; ACTIVE SPECIFIC IMMUNOTHERAPY; NODE-NEGATIVE MELANOMA; ADJUVANT IMMUNOTHERAPY; INTERMEDIATE-THICKNESS; MALIGNANT-MELANOMA; ONCOLOGY-GROUP; TUMOR VACCINE; THERAPY; ALPHA AB Purpose To compare the overall survival (OS) of patients with resected stage III melanoma administered active specific immunotherapy and low-dose interferon alfa-2b (IFN-alpha-2b) with the OS achieved using high-dose IFN-alpha-2b. Patients and Methods An Ad Hoc Melanoma Working Group of 25 investigators treated 604 patients from April 1997 to January 2003. Patients were stratified by sex and number of nodes and were randomly assigned to receive either 2 years of treatment with active specific immunotherapy with allogeneic melanoma lysates and low-dose IFN-alpha-2b (arm 1) or high-dose IFN-alpha-2b alone for 1 year (arm 2). Active specific immunotherapy was injected subcutaneously (SC) weekly for 4 weeks, at week 8, and bimonthly thereafter. IFN-alpha-2b SIC was begun on week 4 and continued thrice weekly at 5 MU/m(2) for 2 years. IFN-alpha-2b in arm 2 was administered according to the Eastern Cooperative Oncology Group 1684 study regimen. Results Median follow-up time was 32 months for all patients and 42 months for surviving patients. Median OS time exceeds 84 months in arm 1 and is 83 months in arm 2 (P =.56). Five-year OS rate is 61% in arm 1 and 57% in arm 2. Estimated 5-year relapse-free survival (RFS) rate is 50% in arm 1 and 48% in arm 2, with median RFS times of 58 and 50 months, respectively. The incidence of serious adverse events as a result of treatment was the same in both arms, but more severe neuropsychiatric toxicity was seen in arm 2. Conclusion OS and RFS achieved by active specific immunotherapy and low-dose IFN-alpha-2b were indistinguishable from those achieved by high-dose IFN-alpha-2b. Long RFS and OS times were observed in both treatment arms. C1 Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Univ Calif San Diego, Ctr Canc, San Diego, CA 92103 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. Ctr Canc, San Francisco, CA USA. Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. Ctr Canc, Irvine, CA USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. St Johns Hosp, Van Elslander Canc Ctr, Grosse Pointe Woods, MI USA. Univ Washington, Sch Med, Seattle, WA USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Yale Univ, Ctr Comprehens Canc, New Haven, CT USA. Harvard Univ, Sch Med, Beth Israel Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Melanoma Ctr St Louis, St Louis, MO USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Hanover, NH USA. Univ Illinois, Chicago, IL USA. Oncol Specialists, Park Ridge, IL USA. Univ Utah, Huntsman Canc Ctr, Salt Lake City, UT USA. Lone Star Oncol, Austin, TX USA. Maine Ctr Canc Med, Scarborough, ME USA. Univ Minnesota, Minneapolis, MN USA. RP Mitchell, MS (reprint author), Univ Texas, 500 Univ Ave, El Paso, TX 79968 USA. EM malcolmsmitcheil@yahoo.com OI Samlowski, Wolfram/0000-0002-0713-914X NR 28 TC 47 Z9 50 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2007 VL 25 IS 15 BP 2078 EP 2085 DI 10.1200/JCO.2006.10.1709 PG 8 WC Oncology SC Oncology GA 172KW UT WOS:000246804200022 PM 17513813 ER PT J AU Asch, DA Armstrong, K AF Asch, David A. Armstrong, Katrina TI Aggregating and partitioning populations in health care disparities research: Differences in perspective SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article AB Health and health care are distributed unevenly across individuals and populations, and identifying these disparities is the first step toward remedying them. We reveal how conceptual and statistical challenges make even the identification of disparities difficult. These difficulties arise because the social, biologic, and environmental causes of disparities are intertwined, leading to statistical confounding. These difficulties arise also because the same data can be analyzed to examine care from the perspective of the patient, or from the perspective of organizations such as health systems or jurisdictions, and these alternative perspectives can yield contradictory results. The result is that health care disparities can be challenging to interpret unless the analytic and policy perspective is clear. C1 Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Asch, DA (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, 3641 Locust Walk, Philadelphia, PA 19104 USA. EM asch@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X NR 9 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2007 VL 25 IS 15 BP 2117 EP 2121 DI 10.1200/JCO.2006.09.3336 PG 5 WC Oncology SC Oncology GA 172KW UT WOS:000246804200027 PM 17513818 ER PT J AU Hudis, CA Barlow, WE Costantino, JP Gray, RJ Pritchard, KI Chapman, JAW Sparano, JA Hunsberger, S Enos, RA Gelber, RD Zujewski, JA AF Hudis, Clifford A. Barlow, William E. Costantino, Joseph P. Gray, Robert J. Pritchard, Kathleen I. Chapman, Judith-Anne W. Sparano, Joseph A. Hunsberger, Sally Enos, Rebecca A. Gelber, Richard D. Zujewski, Jo Anne TI Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: The STEEP system SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; TAMOXIFEN THERAPY; ANASTROZOLE; LETROZOLE AB Purpose Standardized definitions of breast cancer clinical trial end points must be adopted to permit the consistent interpretation and analysis of breast cancer clinical trials and to facilitate cross-trial comparisons and meta-analyses. Standardizing terms will allow for uniformity in data collection across studies, which will optimize clinical trial utility and efficiency. A given end point term (eg, overall survival) used in a breast cancer trial should always encompass the same set of events (eg, death attributable to breast cancer, death attributable to cause other than breast cancer, death from unknown cause), and, in turn, each event within that end point should be commonly defined across end points and studies. Methods A panel of experts in breast cancer clinical trials representing medical oncology, biostatistics, and correlative science convened to formulate standard definitions and address the confusion that nonstandard definitions of widely used end point terms for a breast cancer clinical trial can generate. We propose standard definitions for efficacy end points and events in early-stage adjuvant breast cancer clinical trials. In some cases, it is expected that the standard end points may not address a specific trial question, so that modified or customized end points would need to be prospectively defined and consistently used. Conclusion The use of the proposed common end point definitions will facilitate interpretation of trial outcomes. This approach may be adopted to develop standard outcome definitions for use in trials involving other cancer sites. C1 Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, New York, NY 10021 USA. Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. Canc Res & Biostat, Seattle, WA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Biostat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Div Canc Treatment & Diag, Biometr Res Branch, Rockville, MD USA. EMMES Corp, Rockville, MD USA. NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Rockville, MD USA. Univ Toronto, Toronto, ON, Canada. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Queens Univ, Kingston, ON, Canada. RP Hudis, CA (reprint author), Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, 1275 York Ave,Box 206, New York, NY 10021 USA. EM hudisc@mskcc.org NR 7 TC 273 Z9 276 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2007 VL 25 IS 15 BP 2127 EP 2132 DI 10.1200/JCO.2006.10.3523 PG 6 WC Oncology SC Oncology GA 172KW UT WOS:000246804200029 PM 17513820 ER PT J AU Dawson, S Gould, DA AF Dawson, Steven Gould, Derek A. TI Procedural simulation's developing role in medicine SO LANCET LA English DT Editorial Material ID EDUCATION C1 Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02139 USA. Royal Liverpool Univ Trust, Dept Radiol, Liverpool, Merseyside, England. RP Dawson, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02139 USA. EM sdawson@partners.org NR 8 TC 11 Z9 11 U1 6 U2 6 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 20 PY 2007 VL 369 IS 9574 BP 1671 EP 1673 DI 10.1016/S0140-6736(07)60760-0 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 169ZT UT WOS:000246631300007 PM 17512839 ER PT J AU Cuzick, J Ambroisine, L Davidson, N Jakesz, R Kaufmann, M Regan, M Sainsbury, R AF Cuzick, J. Ambroisine, L. Davidson, N. Jakesz, R. Kaufmann, M. Regan, M. Sainsbury, R. CA LHRH agonists Early Breast Canc Ov TI Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials SO LANCET LA English DT Article ID QUALITY-OF-LIFE; RESEARCH-ASSOCIATION; OVARIAN SUPPRESSION; GOSERELIN; CHEMOTHERAPY; CYCLOPHOSPHAMIDE; FLUOROURACIL; METHOTREXATE; THERAPY; TAMOXIFEN AB Background Several trials have been done to assess treatment of premenopausal breast cancer with luteinising-hormone-releasing hormone (LHRH) agonists, but results have been inconclusive, especially for patients with hormone-receptor-positive cancer. Methods We collected individual patients' data from published trials and did analyses focused on women with tumours positive for oestrogen receptor, progesterone receptor, or both. The main endpoints were recurrence and death after recurrence. Findings We obtained data for 11906 premenopausal women with early breast cancer randomised in 16 trials. When used as the only systemic adjuvant treatment, LHRH agonists did not significantly reduce recurrence (28.4% relative reduction, 95% CI consistent with 50.5% reduction to 3.5% increase, p=0.08) or death after recurrence (17.8%, 52.8% reduction to 42.9% increase, p=0.49) in hormone-receptor-positive cancers. Addition of LHRH agonists to tamoxifen, chemotherapy, or both reduced recurrence by 12.7% (2.4-21.9, p=0.02); and death after recurrence by 15.1% (1.8-26.7, p=0.03). LHRH agonists showed similar efficacy to chemotherapy (recurrence 3.9% increase, 7.7% reduction to 17.0% increase; death after recurrence 6.7% reduction, 20.7% reduction to 9.6% increase; both not significant). No trials had assessed an LHRH agonist versus chemotherapy with tamoxifen in both arms. LHRH agonists were ineffective in hormone-receptor-negative tumours. Interpretation LHRH agonists provide an additional class of agents for treatment of premenopausal women with hormone-receptor-positive breast cancer. Optimum duration of use is unknown. C1 Univ London, Queen Marys Sch Med & Dent, Canc Res UK Ctr Epidemiol Math & Stat, Wolfson Inst Prevent Med, London EC1M 6BQ, England. Johns Hopkins Univ, Sydney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Med Univ Vienna, Vienna, Austria. Goethe Univ Frankfurt, Frauenklin, D-6000 Frankfurt, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. UCL, Dept Surg, London, England. RP Cuzick, J (reprint author), Univ London, Queen Marys Sch Med & Dent, Canc Res UK Ctr Epidemiol Math & Stat, Wolfson Inst Prevent Med, London EC1M 6BQ, England. EM jack.cuzick@cancer.org.uk NR 23 TC 194 Z9 209 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAY 20 PY 2007 VL 369 IS 9574 BP 1711 EP 1723 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 169ZT UT WOS:000246631300027 ER PT J AU Rubin, BP Heinrich, MC Corless, CL AF Rubin, Brian P. Heinrich, Michael C. Corless, Christopher L. TI Gastrointestinal stromal tumour SO LANCET LA English DT Review ID C-KIT GENE; RECEPTOR TYROSINE KINASE; TERM-FOLLOW-UP; AUTONOMIC NERVE TUMORS; OF-FUNCTION MUTATIONS; BONE-SARCOMA-GROUP; EORTC-SOFT-TISSUE; GERMLINE MUTATION; IMATINIB MESYLATE; INTERSTITIAL-CELLS AB Gastrointestinal stromal tumours are the most common mesenchymal neoplasm of the gastrointestinal tract and are highly resistant to conventional chemotherapy and radiotherapy. Such tumours usually have activating mutations in either KIT (75-80%) or PDGFRA (5-10%), two closely related receptor tyrosine kinases. These mutations lead to ligand-independent activation and signal transduction mediated by constitutively activated KIT or PDGFRA. Targeting these activated proteins with imatinib mesylate, a small-molecule kinase inhibitor, has proven useful in the treatment of recurrent or metastatic gastrointestinal stromal tumours and is now being tested as an adjuvant or neoadjuvant. However, resistance to imatinib is a growing problem and other targeted therapeutics such as sunitinib are available. The important interplay between the molecular genetics of gastrontestinal stromal turnout and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumours. C1 Cleveland Clin Fdn, Dept Anat Pathol, Taussig Canc Ctr, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Mol Genet, Taussig Canc Ctr, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. Oregon Hlth & Sci Univ, Inst Canc, Dept Pathol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Inst Canc, Dept Med, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Inst Canc, Dept Cell & Dev Biol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. RP Rubin, BP (reprint author), Cleveland Clin Fdn, Dept Anat Pathol, Taussig Canc Ctr, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM rubinb2@ccf.org NR 135 TC 267 Z9 302 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY 20 PY 2007 VL 369 IS 9574 BP 1731 EP 1741 DI 10.1016/S0140-6736(07)60780-6 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 169ZT UT WOS:000246631300029 PM 17512858 ER PT J AU Harel, O Zhou, XH AF Harel, Ofer Zhou, Xiao-Hua TI Multiple imputation for the comparison of two screening tests in two-phase Alzheimer studies SO STATISTICS IN MEDICINE LA English DT Article DE missing data; multiple imputation; verification bias; two-phase studies ID CORRELATED BINARY PROPORTIONS; CONFIDENCE-INTERVALS; BINOMIAL PROPORTIONS; VERIFICATION BIAS; DIAGNOSTIC-TESTS; PAIRED DATA; DIFFERENCE; DISTRIBUTIONS; SELECTION; DEMENTIA AB Two-phase designs are common in epidemiological studies of dementia, and especially in Alzheimer research. In the first phase, all subjects are screened using a common screening test(s), while in the second phase, only a subset of these subjects is tested using a more definitive verification assessment, i.e. golden standard test. When comparing the accuracy of two screening tests in a two-phase study of dementia, inferences are commonly made using only the verified sample. It is well documented that in that case, there is a risk for bias, called verification bias. When the two screening tests have only two values (e.g. positive and negative) and we are trying to estimate the differences in sensitivities and specificities of the tests, one is actually estimating a confidence interval for differences of binomial proportions. Estimating this difference is not trivial even with complete data. It is well documented that it is a tricky task. In this paper, we suggest ways to apply imputation procedures in order to correct the verification bias. This procedure allows us to use well-established complete-data methods to deal with the difficulty of the estimation of the difference of two binomial proportions in addition to dealing with incomplete data. We compare different methods of estimation and evaluate the use of multiple imputation in this case. Our simulation results show that the use of multiple imputation is superior to other commonly used methods. We demonstrate our finding using Alzheimer data. Copyright (C) 2006 John Wiley & Sons, Ltd. C1 Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. RP Harel, O (reprint author), Univ Connecticut, Dept Stat, 215 Glenbrook Rd,Unit 4120, Storrs, CT 06269 USA. EM oharel@stat.uconn.edu FU NIMH NIH HHS [K01 MH087219] NR 29 TC 10 Z9 10 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 20 PY 2007 VL 26 IS 11 BP 2370 EP 2388 DI 10.1002/sim.2715 PG 19 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 163LN UT WOS:000246161400006 PM 17054089 ER PT J AU Liang, HY Van Remmen, H Frohlich, V Lechleiter, J Richardson, A Ran, QT AF Liang, Hanyu Van Remmen, Holly Frohlich, Victoria Lechleiter, James Richardson, Arlan Ran, Qitao TI Gpx4 protects mitochondrial ATP generation against oxidative damage SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE glutathione peroxidase 4; mitochondria; oxidative stress; ATP production; transgenic mice ID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; HYPOGLYCEMIA-INDUCED APOPTOSIS; PERMEABILITY TRANSITION; HYDROGEN-PEROXIDE; CYTOCHROME-C; CELLS; CARDIOLIPIN; OXYGEN; STRESS; INJURY AB Mitochondrial ATP production can be impaired by oxidative stress. Glutathione peroxidase 4 (Gpx4) is an antioxidant defense enzyme found in mitochondria as well as other subcellular organelles that directly detoxifies membrane lipid hydroperoxides. To determine if Gpx4 protects ATP production in vivo, we compared mitochondrial ATP production between wild-type mice and Gpx4 transgenic mice using a diquat model. Diquat (50 mg/kg) significantly decreased mitochondrial ATP synthesis in livers of wild-type mice; however, no decrease in mitochondrial ATP synthesis was detected in Gpx4 transgenic mice after diquat. We observed no differences in activities of mitochondrial respiratory chain complexes between Gpx4 transgenic mice and wild-type mice. However, compared to wild-type mice, diquat-induced loss of mitochondrial membrane potential was attenuated in Gpx4 transgenic mice. Therefore, our results indicate that decreased ATP production under oxidative stress is primarily due to reduced mitochondrial membrane potential and overexpression of Gpx4 maintains mitochondrial membrane potential under oxidative stress. (c) 2007 Published by Elsevier Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. RP Ran, QT (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM ran@uthscsa.edu RI Liang, Hanyu/A-1066-2010 FU NIA NIH HHS [1P30-AG13319, P01 AG19316, P01AG020591] NR 39 TC 42 Z9 50 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 18 PY 2007 VL 356 IS 4 BP 893 EP 898 DI 10.1016/j.bbrc.2007.03.045 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 158ZD UT WOS:000245833500011 PM 17395155 ER PT J AU Lee-Huang, S Huang, PL Zhang, DW Lee, JW Bao, J Sun, YT Chang, YT Zhang, J Huang, PL AF Lee-Huang, Sylvia Huang, Philip Lin Zhang, Dawei Lee, Jae Wook Bao, Ju Sun, Yongtao Chang, Young-Tae Zhang, John Huang, Paul Lee TI Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: Part 1. Integrase inhibition (vol 354, pg 872, 2007) SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Correction C1 NYU, Sch Med, Dept Biochem, New York, NY 10006 USA. Amer Biosci, Boston, MA 02114 USA. NYU, Dept Chem, New York, NY 10003 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Lee-Huang, S (reprint author), NYU, Sch Med, Dept Biochem, New York, NY 10006 USA. EM sylvia.lee-huang@med.nyu.edu RI Bao, Ju/E-6242-2012; OI Lee-Huang, Sylvia/0000-0003-3302-241X NR 1 TC 0 Z9 0 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 18 PY 2007 VL 356 IS 4 BP 1068 EP 1068 DI 10.1016/j.bbrc.2007.03.022 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 158ZD UT WOS:000245833500039 ER PT J AU Kuperberg, GR AF Kuperberg, Gina R. TI Neural mechanisms of language comprehension: Challenges to syntax SO BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the International-Cognitive-Neuroscience-Society (ICON 9) CY 2006 CL San Francisco, CA SP Int Congnit Neurosci Soc, Elsevier, Univ Calif Davis, Ctr Mind & Brain DE language; N400; P600; ERP; semantic; snytax; thematic role ID EVENT-RELATED POTENTIALS; INFERIOR PREFRONTAL CORTEX; RIGHT CEREBRAL HEMISPHERES; LATENT SEMANTIC ANALYSIS; BRAIN POTENTIALS; SENTENCE COMPREHENSION; THOUGHT-DISORDER; LEXICAL DECISION; FUNCTIONAL MRI; POSITIVE SHIFT AB In 1980, the N400 event-related potential was described in association with semantic anomalies within sentences. When, in 1992, a second waveform, the P600, was reported in association with syntactic anomalies and ambiguities, the story appeared to be complete: the brain respected a distinction between semantic and syntactic representation and processes. Subsequent. studies showed that the P600 to syntactic anomalies and ambiguities was modulated by lexical and discourse factors. Most surprisingly, more than a decade after the P600 was first described, a series of studies reported that semantic verb-argument violations, in the absence of any violations or ambiguities of syntax can evoke robust P600 effects and no N400 effects. These observations have raised fundamental questions about the relationship between semantic and syntactic processing in the brain. This paper provides a comprehensive review of the recent studies that have demonstrated P600s to semantic violations in light of several proposed triggers: semantic-thematic attraction, semantic associative relationships, animacy and semantic-thematic violations, plausibility, task, and context. I then discuss these findings in relation to a unifying theory that attempts to bring some of these factors together and to link the P600 produced by semantic verb-argument violations with the P600 evoked by unambiguous syntactic violations and syntactic ambiguities. I suggest that normal language comprehension proceeds along at least two competing neural processing streams: a semantic memory-based mechanism, and a combinatorial mechanism (or mechanisms) that assigns structure to a sentence primarily on the basis of morphosyntactic rules, but also on the basis of certain semantic-thematic constraints. I suggest that conflicts between the different representations that are output by these distinct but interactive streams lead to a continued combinatorial analysis that is reflected by the P600 effect. I discuss some of the implications of this non-syntactocentric, dynamic model of language processing for understanding individual differences, language processing disorders and the neuroanatomical circuitry engaged during language comprehension. Finally, I suggest that that these two processing streams may generalize beyond the language system to real-world visual event comprehension. (c) 2007 Published by Elsevier B.V. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Kuperberg, GR (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02155 USA. EM kuperber@nmr.mgh.harvard.edu FU NIMH NIH HHS [R01 MH071635] NR 161 TC 324 Z9 333 U1 6 U2 48 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 18 PY 2007 VL 1146 SI SI BP 23 EP 49 DI 10.1016/j.brainres.2006.12.063 PG 27 WC Neurosciences SC Neurosciences & Neurology GA 168AK UT WOS:000246494200003 PM 17400197 ER PT J AU Oviedo, NJ Levin, M AF Oviedo, Nestor J. Levin, Michael TI Gap junctions provide new links in left-right patterning SO CELL LA English DT Editorial Material ID CAENORHABDITIS-ELEGANS; ASYMMETRY AB Gap junctions are increasingly recognized as key regulators of embryonic development, nervous system function, and neoplasia. Chuang et al. (2007) now show that developing neural circuits use communication through gap junctions to establish left-right asymmetry in the central nervous system of the worm Caenorhabditis elegans, revealing that nematodes share a mechanism for left-right asymmetry in common with vertebrates. C1 Forsyth Inst, Forsyth Ctr Regenerat & Dev Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Forsyth Inst, Forsyth Ctr Regenerat & Dev Biol, 140 The Fenway, Boston, MA 02115 USA. EM mievin@forsyth.org FU NIGMS NIH HHS [F32 GM078774-02, F32 GM078774-01A1, F32 GM078774] NR 8 TC 19 Z9 19 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 18 PY 2007 VL 129 IS 4 BP 645 EP 647 DI 10.1016/j.cell.2007.05.005 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 172FA UT WOS:000246788300006 PM 17512395 ER PT J AU Moldovan, GL Pfander, B Jentsch, S AF Moldovan, George-Lucian Pfander, Boris Jentsch, Stefan TI PCNA, the maestro of the replication fork SO CELL LA English DT Review ID CELL NUCLEAR ANTIGEN; DNA-POLYMERASE-DELTA; ASSEMBLY FACTOR-I; MISMATCH-REPAIR; LIGASE-I; SACCHAROMYCES-CEREVISIAE; PHYSICALLY INTERACTS; FACTOR-C; MONOUBIQUITINATED PCNA; FLAP ENDONUCLEASE-1 AB Inheritance requires genome duplication, reproduction of chromatin and its epigenetic information, mechanisms to ensure genome integrity, and faithful transmission of the information to progeny. Proliferating cell nuclear antigen (PCNA)-a cofactor of DNA polymerases that encircles DNA-orchestrates several of these functions by recruiting crucial players to the replication fork. Remarkably, many factors that are involved in replication-linked processes interact with a particular face of PCNA and through the same interaction domain, indicating that these interactions do not occur simultaneously during replication. Switching of PCNA partners may be triggered by affinity-driven competition, phosphorylation, proteolysis, and modification of PCNA by ubiquitin and SUMO. C1 Max Planck Inst Biochem, Dept Mol Cell Biol, D-82152 Martinsried, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Canc Res UK, Clare Hall Labs, S Mimms EH6 3LD, Herts, England. RP Jentsch, S (reprint author), Max Planck Inst Biochem, Dept Mol Cell Biol, Am Klopferspitz 18, D-82152 Martinsried, Germany. EM jentsch@biochem.mpg.de RI Pfander, Boris/A-8703-2013; OI George-Lucian, Moldovan/0000-0003-3825-149X NR 105 TC 820 Z9 845 U1 17 U2 88 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 18 PY 2007 VL 129 IS 4 BP 665 EP 679 DI 10.1016/j.cell.2007.05.003 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 172FA UT WOS:000246788300013 PM 17512402 ER PT J AU Zhang, LF Huynh, KD Lee, JT AF Zhang, Li-Feng Huynh, Khanh D. Lee, Jeannie T. TI Perinucleolar targeting of the inactive X during S phase: Evidence for a role in the maintenance of silencing SO CELL LA English DT Article ID EARLY MOUSE EMBRYOS; TRANSFER-RNA GENES; CHROMOSOME INACTIVATION; DNA-REPLICATION; HUMAN-FIBROBLASTS; XIST GENE; INTERPHASE; TSIX; LOCALIZATION; CELL AB In mammalian females, two X chromosomes are epigenetically distinguished as active and inactive chromosomes to balance X-linked gene dosages between males and females. How the Xs are maintained differently in the same nucleus remains unknown. Here, we demonstrate that the inactive X (Xi) is targeted to a distinct nuclear compartment following pairing with its homologous partner. During mid-to-late S phase, 80%-90% of Xi contact the nucleolus and reside within a Snf2h-enriched ring. Autosomes carrying ectopic X-inactivation center sequences are also targeted to the perinucleolar compartment. Deleting Xist results in a loss of nucleolar association and an inability to maintain Xi heterochromatin, leading to Xi reactivation at the single gene level. We propose that the Xi must continuously visit the perinucleolar compartment to maintain its epigenetic state. These data raise a mechanism by which chromatin states can be replicated by spatial and temporal separation in the nucleus. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Zhang, Li-Feng/0000-0003-0917-0017 FU NCI NIH HHS [K01-CA115593]; NIGMS NIH HHS [R01-GM58839] NR 48 TC 155 Z9 158 U1 1 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 18 PY 2007 VL 129 IS 4 BP 693 EP 706 DI 10.1016/j.cell.2007.03.036 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 172FA UT WOS:000246788300015 PM 17512404 ER PT J AU Engelman, JA Zejnullahu, K Mitsudomi, T Song, YC Hyland, C Park, JO Lindeman, N Gale, CM Zhao, XJ Christensen, J Kosaka, T Holmes, AJ Rogers, AM Cappuzzo, F Mok, T Lee, C Johnson, BE Cantley, LC Janne, PA AF Engelman, Jeffrey A. Zejnullahu, Kreshnik Mitsudomi, Tetsuya Song, Youngchul Hyland, Courtney Park, Joon Oh Lindeman, Neal Gale, Christopher-Michael Zhao, Xiaojun Christensen, James Kosaka, Takayuki Holmes, Alison J. Rogers, Andrew M. Cappuzzo, Federico Mok, Tony Lee, Charles Johnson, Bruce E. Cantley, Lewis C. Janne, Pasi A. TI MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling SO SCIENCE LA English DT Article ID GROWTH-FACTOR-RECEPTOR; GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE; ACQUIRED-RESISTANCE; IMATINIB MESYLATE; INHIBITOR; MUTATIONS; THERAPY; GENE; ADENOCARCINOMA AB The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Signal Transduct, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Aichi Canc Ctr Hosp, Dept Thorac Surg, Nagoya, Aichi 4648681, Japan. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Pfizer Global Res & Dev, Dept Res Pharmacol, San Diego, CA 92121 USA. Ist Clin Humanitas, Dept Hematol Oncol, I-20089 Rozzano, Italy. Chinese Univ Hong Kong, Dept Clin Oncol, Shatin, Hong Kong, Peoples R China. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. EM pjanne@partners.org RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Cappuzzo, Federico/0000-0002-6295-6767; Mitsudomi, Tetsuya/0000-0001-9860-8505 FU NCI NIH HHS [K08CA120060-01, P01 CA089021, P20CA90578-02, R01-CA111560, R01CA114465-01, 1K12CA87723-01]; NIGMS NIH HHS [GM41890, R01 GM041890] NR 22 TC 2295 Z9 2380 U1 31 U2 220 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 18 PY 2007 VL 316 IS 5827 BP 1039 EP 1043 DI 10.1126/science.1141478 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 168WF UT WOS:000246554000050 PM 17463250 ER PT J AU Wechsler, ME Shepard, JAO Mark, EJ AF Wechsler, Michael E. Shepard, Jo-Anne O. Mark, Eugene J. TI Woman with asthma and cardiorespiratory arrest - Status asthmaticus with hyperinflated lungs, pleural and pericardial interstitial emphysema, mucus plugging, bronchiolar scarring, and eosinophilic pneumonitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INHALED CORTICOSTEROIDS; FATAL ASTHMA; CONTROLLED-TRIAL; EXACERBATIONS; SALMETEROL; RECEPTOR; AIRWAYS; POLYMORPHISMS; OMALIZUMAB; ALBUTEROL C1 Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wechsler, ME (reprint author), Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, 75 Francis St, Boston, MA 02115 USA. RI Wechsler, Michael /B-3979-2013 OI Wechsler, Michael /0000-0003-3505-2946 NR 40 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 17 PY 2007 VL 356 IS 20 BP 2083 EP 2091 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 167ZD UT WOS:000246490500011 PM 17507708 ER PT J AU Swisher, JD Halko, MA Merabet, LB McMains, SA Somers, DC AF Swisher, Jascha D. Halko, Mark A. Merabet, Lotfi B. McMains, Stephanie A. Somers, David C. TI Visual topography of human intraparietal sulcus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retinotopy; parietal cortex; individual differences; vision; multisensory; tactile ID POSTERIOR PARIETAL CORTEX; SURFACE-BASED ANALYSIS; SHORT-TERM-MEMORY; SPATIAL ATTENTION; FUNCTIONAL-ORGANIZATION; MACAQUE MONKEYS; STRIATE CORTEX; HUMAN BRAIN; AREAS; FMRI AB Human parietal cortex is implicated in a wide variety of sensory and cognitive functions, yet its precise organization remains unclear. Visual field maps provide a potential structural basis for descriptions of functional organization. Here, we detail the topography of a series of five maps of the contralateral visual hemifield within human posterior parietal cortex. These maps are located along the medial bank of the intraparietal sulcus (IPS) and are revealed by direct visual stimulation during functional magnetic resonance imaging, allowing these parietal regions to be routinely and reliably identified simultaneously with occipital visual areas. Two of these maps (IPS3 and IPS4) are novel, whereas two others (IPS1 and IPS2) have previously been revealed only by higher-order cognitive tasks. Area V7, a previously identified visual map, is observed to lie within posterior IPS and to share a foveal representation with IPS1. These parietal maps are reliably observed across scan sessions; however, their precise topography varies between individuals. The multimodal organization of posterior IPS mirrors this variability in visual topography, with complementary tactile activations found immediately adjacent to the visual maps both medially and laterally. These visual maps may provide a practical framework in which to characterize the functional organization of human IPS. C1 Boston Univ, Program Neurosci, Perceptual Neuroimaging Lab, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Ctr Noninvas Brain Stimulat, Boston, MA 02115 USA. Princeton Univ, Dept Psychol, Neurosci Attent & Percept Lab, Princeton, NJ 08544 USA. Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Swisher, JD (reprint author), Boston Univ, Program Neurosci, Perceptual Neuroimaging Lab, 2 Cummington St, Boston, MA 02215 USA. EM swisher@mind.bu.edu RI Somers, David/G-5802-2010; Halko, Mark/G-8633-2016; OI Halko, Mark/0000-0002-7427-0789; Somers, David/0000-0002-4169-5895 FU NEI NIH HHS [K23 EY016131-01] NR 80 TC 239 Z9 239 U1 3 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 16 PY 2007 VL 27 IS 20 BP 5326 EP 5337 DI 10.1523/JNEUROSCI.0991-07.2007 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 171FL UT WOS:000246720600008 PM 17507555 ER PT J AU El-Serag, HB Lau, M AF El-Serag, H. B. Lau, M. TI Temporal trends in new and recurrent oesophageal strictures in a Medicare population SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GASTROESOPHAGEAL-REFLUX-DISEASE; PROTON PUMP INHIBITORS; BARRETTS-ESOPHAGUS; CONCEPTUAL-FRAMEWORK; OMEPRAZOLE; DYSPLASIA; THERAPY AB Background The widespread use of proton pump inhibitors for gastro-oesophageal reflux disease could result in a decline in new as well as recurrent gastro-oesophageal reflux disease-related oesophageal strictures. The temporal trends of strictures have not been examined in population-based studies. Methods To examine the temporal trends in strictures, we calculated the age-adjusted incidence rates of new oesophageal strictures with or without oesophageal dilation in a sample of Medicare beneficiaries between 1992 and 2000. We also examined recurrent dilations recorded at least 3 months after a new stricture or the preceding recurrent stricture. Results The age-adjusted rates for strictures accompanied with dilation declined by approximately 11% from 215 per million to 192 per million. New oesophageal strictures with dilation declined as a proportion of all upper endoscopies procedures (from 2.6% to 1.9%). Recurrent dilation within 1 year declined dramatically from 16% (9.5% CI: 12.5 - 20.3) in 1992 to 8% ( 95% CI: 4.43 - 10.62) in 2000. In multivariable proportional hazards model, there was a 30% risk reduction of recurrent oesophageal strictures. Conclusions This population-based study indicates that the incidence of new as well as recurrent oesophageal strictures has been declining. In the face of rising incidence of other gastro-oesophageal reflux disease-related complications, it is important to understand the explanation of the present observations. C1 Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Gastroenterol Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 15 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD MAY 15 PY 2007 VL 25 IS 10 BP 1223 EP 1229 DI 10.1111/j.1365-2036.2007.03310.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 160JX UT WOS:000245937800009 PM 17451568 ER PT J AU Bennett, KM Hernandez, AF Chen, AY Mulgund, J Newby, L Rumsfeld, JS Hochman, JS Hoekstra, JW Ohman, EM Gibler, WB Roe, MT Peterson, ED AF Bennett, Kyla M. Hernandez, Adrian F. Chen, Anita Y. Mulgund, Jyotsna Newby, L. Kristin Rumsfeld, John S. Hochman, Judith S. Hoekstra, James W. Ohman, E. Magnus Gibler, W. Brian Roe, Matthew T. Peterson, Eric D. TI Heart failure with preserved left ventricular systolic function among patients with non-ST-segment elevation acute coronary syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; NATIONAL-REGISTRY; CLINICAL-EVIDENCE; GUIDELINE UPDATE; VALIANT REGISTRY; DYSFUNCTION; MORBIDITY; MANAGEMENT; MORTALITY AB Previous studies of non-ST-segment elevation acute coronary syndromes (NSTE ACSs) complicated by heart failure (HF) have focused primarily on patients with left ventricular systolic dysfunction defined by an ejection fraction (EF) <40%. Little is known about HF with preserved systolic function (EF >= 40%) in the NSTE ACS population. We identified high-risk patients with NSTE ACS (ischemic electrocardiographic changes and/or positive cardiac markers) from the CRUSADE quality improvement initiative who had an EF recorded and who had information on HF status. Management and outcomes were analyzed and compared based on the presence or absence of HF and whether left ventricular EF was >= 40%. Of 94,558 patients with NSTE ACS, 21,561 (22.8%) presented with signs of HF, and most had HF with preserved systolic function (n = 11,860,'55%). Mortality rates were 10.7% for HF/systolic dysfunction, 5.8% for HF/preserved systolic function, 5.7% for no HF/systolic dysfunction, and 1.5% for no HF/preserved systolic function. Use of guideline-recommended medical therapies and interventions was frequently significantly lower in those with HF regardless of EF compared with those without HF, except for use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. In conclusion, NSTE ACS complicated by HF with preserved systolic function is common and associated with a 2.3-fold higher mortality compared with NSTE ACS without HF or systolic dysfunction. Guideline-recommended therapies and interventions are under-utilized in patients with NSTE ACS and HF, with and without preserved systolic function, compared with those without HF. (c) 2007 Elsevier Inc. All rights reserved. C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80202 USA. NYU, Sch Med, New York, NY USA. Univ Cincinnati, Sch Med, Cincinnati, OH 45221 USA. RP Hernandez, AF (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. EM herna014@mc.duke.edu RI Hernandez, Adrian F./A-7818-2016; OI Hernandez, Adrian F./0000-0003-3387-9616; Hochman, Judith/0000-0002-5889-5981 NR 24 TC 10 Z9 13 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2007 VL 99 IS 10 BP 1351 EP 1356 DI 10.1016/j.amjcard.2006.12.057 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 171DU UT WOS:000246715900001 PM 17493458 ER PT J AU Cavusoglu, E Ruwende, C Eng, C Chopra, V Yanamadala, S Clark, LT Pinsky, DJ Marmur, JD AF Cavusoglu, Erdal Ruwende, Cyril Eng, Calvin Chopra, Vineet Yanamadala, Sunitha Clark, Luther T. Pinsky, David J. Marmur, Jonathan D. TI Usefulness of baseline plasma myeloperoxidase levels as an independent predictor of myocardial infarction at two years in patients presenting with acute coronary syndrome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC HEART-FAILURE; CARDIAC MORTALITY; PROGNOSTIC VALUE; CHEST-PAIN; ASSOCIATION; ADIPONECTIN; DISEASE; RISK AB Baseline plasma myeloperoxidase (MPO) levels have been shown to independently predict the early risk of myocardial infarction (MI) in patients presenting with chest pain. In addition, baseline MPO levels have been demonstrated to predict the development of adverse cardiac events up to 6 months after an acute coronary syndrome (ACS). However, in contrast to other biomarkers, there are no data about the long-term independent predictive value of baseline MPO values in patients with ACS. The present study investigated the long-term prognostic significance of baseline MPO levels in a well-characterized cohort of 193 men with ACS who were referred for coronary angiography at a Veterans Administration Medical Center. All patients were followed prospectively for the development of death and MI, and follow-up data were available for all patients at 24 months. After controlling for different baseline clinical, laboratory, and angiographic variables, baseline plasma MPO values were a strong and independent predictor of MI at 24 months by multivariate analysis. Using the median MPO value of the entire cohort of patients (i.e., 20.34 ng/ml) as a prespecified cutoff, the MI-free survival at 24 months for the group whose baseline MPO values were <= 20.34 ng/ml was 88% compared with 74% in those whose values were > 20.34 ng/ml (p = 0.0249 by log-rank test). In conclusion, these data demonstrate that baseline MPO levels independently predict MI at 2 years in patients with ACS. (c) 2007 Elsevier Inc. All rights reserved. C1 Suny Downstate Med Ctr, Div Cardiol, Dept Med, Brooklyn, NY 11203 USA. Bronx Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. RP Cavusoglu, E (reprint author), Suny Downstate Med Ctr, Div Cardiol, Dept Med, Brooklyn, NY 11203 USA. EM ecavusoglu@aol.com NR 17 TC 72 Z9 84 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2007 VL 99 IS 10 BP 1364 EP 1368 DI 10.1016/j.amjcard.2006.12.060 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 171DU UT WOS:000246715900004 PM 17493461 ER PT J AU Tricoci, P Peterson, ED Chen, AY Newby, LK Harrington, RA Greenbaum, AB Cannon, CP Gibson, CM Hoekstra, JW Pollack, CV Ohman, EM Gibler, WB Roe, MT AF Tricoci, Pierluigi Peterson, Eric D. Chen, Anita Y. Newby, L. Kristin Harrington, Robert A. Greenbaum, Adam B. Cannon, Chistopher P. Gibson, C. Michael Hoekstra, James W. Pollack, Charles V., Jr. Ohman, E. Magnus Gibler, W. Brian Roe, Matthew T. TI Timing of glycoprotein IIb/IIIa inhibitor use and outcomes among patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (Results from CRUSADE) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID UNSTABLE ANGINA; TIROFIBAN; TRIAL; MANAGEMENT; EPTIFIBATIDE; ASSOCIATION; COMMITTEE; RECEPTOR AB Although glycoprotein (GP) IIb/IIIa inhibitors are recommended for patients with unstable angina and non-ST-segment elevation myocardial infarction who undergo percutaneous coronary intervention (PCI), the American College of Cardiology/American Heart Association guidelines do not specify optimal timing for their initiation. We compared patient characteristics and clinical outcomes in 30,830 patients with non-ST-segment elevation myocardial infarction included in the CRUSADE initiative (January 2001 to December 2004) who underwent PCI with upstream (> 1 hour before PCI) or periprocedural use of GP IIb/IIIa inhibitors.. GP IIb/IIIa inhibitors were administered upstream in 43% of patients versus periprocedurally in 57%. Time from. arrival to PCI was longer for patients who received GP IIb/IIIa inhibitors upstream (median 25.6 hours) compared with periprocedurally (18.2 hours). Unadjusted incidence of in-hospital death or reinfarction was lower with upstream GP IIb/IIIa inhibitor use (3.8% vs 4.3%, p = 0.046), but after adjusting for patient and hospital characteristics, this difference was not statistically significant. Treatment with upstream GP IIb/IIIa inhibitors was associated with a lower incidence of unadjusted death or reinfarction in patients who underwent PCI < 12 hours from hospital arrival. In conclusion, in this observational analysis, overall ischemic outcomes were similar between the 2 groups, but clinical trials are needed to solve the controversy over optional timing of GP IIb/IIIa inhibitor use. (c) 2007 Elsevier Inc. All rights reserved. C1 Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27706 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Henry Ford Heart & Vasc Inst, Detroit, MI USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Univ Penn, Hlth Syst, Penn Hosp, Philadelphia, PA 19104 USA. Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. RP Tricoci, P (reprint author), Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27706 USA. EM trico001@dcri.duke.edu NR 15 TC 20 Z9 22 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2007 VL 99 IS 10 BP 1389 EP 1393 DI 10.1016/j.amjcard.2006.12.066 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 171DU UT WOS:000246715900009 PM 17493466 ER PT J AU Greenberg, JO Greenberg, H AF Greenberg, Jeffrey O. Greenberg, Henry TI More physicians are not the answer SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID HEART-FAILURE; PRIMARY-CARE; MANAGEMENT; QUALITY AB The Association of American Medical Colleges has called for an increase of 30% in matriculation in United States medical schools to treat the growing number of elderly patients with chronic illnesses. However, increasing the physician supply is unlikely to address the underlying problem, that being the growth of chronic disease, which necessitates a shift in orientation from treatment to management and prevention. This shift will in turn require a change in the makeup of health care providers. Instead of more physicians, more nonphysician professionals must be trained so as to aggressively coordinate comprehensive chronic disease care. A disease management model led by physicians, but including advanced practice nurses and other professionals, offers the opportunity to enhance efficiency, improve quality, reduce hospitalization, and meet evidence-based mandates. Such a workforce transition can become the inaugural step in converting the entire health care system from treatment based to prevention and management based. In conclusion, the position of the Association of American Medical Colleges should be a platform for discussion. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Columbia Univ, Coll Phys & Surg, Dept Med, Div Cardiol,St Lukes Roosevelt Hosp, New York, NY 10027 USA. Columbia Univ, Coll Phys & Surg, Inst Human Nutr, Div Cardiol,St Lukes Roosevelt Hosp, New York, NY 10027 USA. RP Greenberg, JO (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM jogreenberg@partners.org NR 15 TC 6 Z9 6 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 2007 VL 99 IS 10 BP 1476 EP 1478 DI 10.1016/j.amjcard.2006.12.084 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 171DU UT WOS:000246715900028 PM 17493485 ER PT J AU Oh, K Willett, WC Wu, K Fuchs, CS Giovannucci, EL AF Oh, Kyungwon Willett, Walter C. Wu, Kana Fuchs, Charles S. Giovannucci, Edward L. TI Calcium and vitamin D intakes in relation to risk of distal colorectal adenoma in women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adenoma; calcium; vitamin D ID EPITHELIAL-CELL PROLIFERATION; FOOD FREQUENCY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; COLON-CANCER; DAIRY-PRODUCTS; DIETARY CALCIUM; UNITED-STATES; PROSPECTIVE COHORT; ASPIRIN USE; D-RECEPTOR AB The authors examined intakes of calcium and vitamin D, and interaction with retinol, in relation to risk of adenoma of the distal colon or rectum among 48,115 US women who were free of colorectal cancer or polyps, completed a food frequency questionnaire in 1980, and underwent endoscopy by 2002. They documented 2,747 cases of adenoma (1,064 large, 1,531 small, 2,085 distal colon, and 779 rectal). Total calcium intake was weakly associated with distal colorectal adenoma risk (multivariable relative risk (RR) for extreme quintiles = 0.88, 95% confidence interval (CI): 0.74, 1.04; p(trend) = 0.06), particularly for large adenoma (RR = 0.73, 95% CI: 0.56, 0.96; p(trend) = 0.02). Total vitamin D intake was weakly associated with reduced risk of distal colorectal adenoma (RR = 0.79, 95% CI: 0.63, 0.99; p(trend) = 0.07), but more strongly with distal colon adenoma risk (RR = 0.67, 95% CI: 0.52, 0.87; p(trend) = 0.004). The combinations of high vitamin D and low retinol intake (RR = 0.55, 95% CI: 0.28, 1.10) further decreased risk of distal colorectal adenoma when compared with the opposite extreme. Higher total calcium and vitamin D intakes were associated with reduced risk, and the actions of vitamin D may be attenuated by high retinol intake. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Korea Ctr Dis Controll & Prevent, Div Chron Dis Surveillance, Seoul, South Korea. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Giovannucci, EL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM edward.giovannucci@channing.harvard.edu FU NCI NIH HHS [CA 55075, CA 87969]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 59 TC 59 Z9 61 U1 0 U2 1 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 MAY 15 PY 2007 VL 165 IS 10 BP 1178 EP 1186 DI 10.1093/aje/kwm026 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 162WK UT WOS:000246120000011 PM 17379616 ER PT J AU Camargo, CA Ramachandran, S Ryskina, KL Lewis, BE Legorreta, AP AF Camargo, Carlos A., Jr. Ramachandran, Sulabha Ryskina, Kira L. Lewis, Barbara Edelman Legorreta, Antonio P. TI Association between common asthma therapies and recurrent asthma exacerbations in children enrolled in a state Medicaid plan SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE aerosols; asthma; budesonicle; compliance; health-benefit programs; patients; pediatrics; steroids; cortico- ID BUDESONIDE INHALATION SUSPENSION; HEALTH MAINTENANCE ORGANIZATION; PERSISTENT ASTHMA; YOUNG-CHILDREN; CHILDHOOD ASTHMA; ANTIINFLAMMATORY THERAPY; MANAGEMENT GUIDELINES; EMERGENCY-DEPARTMENT; SPECIALTY CARE; HOSPITALIZATION AB Purpose. To evaluate the effectiveness of budesonide inhalation suspension relative to other common asthma therapies in a high-risk population, a study was conducted to compare the risk of having a repeat asthma-related hospitalization or emergency department (ED) visit in a Medicaid population of children; the relationship between asthma medication adherence level and repeat asthma hospitalizations or ED visits was also evaluated. Methods. Children eight years of age or younger, with a hospitalization or ED visit for asthma between January 1999 and June 2001 (index event), were identified in a Florida Medicaid database. Claims data for each child were examined 12 months before and after the index event. Cox proportional hazards regression was used to model the risk of subsequent asthma exacerbation according to the asthma medication received during the first 30 days after the index event. Logistic regression was used to model the relationship between medication adherence as measured by the medication possession ratio (MPR) and the likelihood of a subsequent asthma exacerbation. Results. There were 10,976 children in the study. Patients who had a claim for budesonide inhalation suspension had a lower risk of a subsequent hospitalization or ED visit (hazard ratio, 0.55; 95% confidence interval, 0.41-0.76; p < 0.001) than patients who did not have budesonide inhalation suspension claims. Other controller medications were not associated with a reduction in the risk of subsequent asthma exacerbations. Adherence to medication was poor (a median MPR of 0.08 for budesonide inhalation suspension and a median MPR of 0.16 for any asthma controller medication). The odds of a repeat hospitalization or ED visit were significantly lower for children who were adherent to their asthma controller medication. Conclusion. Children with asthma and insured by Medicaid were at a high risk of repeat exacerbations leading to increased hospitalizations and ED visits. Treatment with budesonide inhalation suspension in the first 30 days after a hospitalization or ED visit for asthma was associated with a significant reduction in the risk of repeat asthma-related hospitalizations or ED visits during the following year. Children who were adherent to their asthma controller medication had significantly lower odds of having a subsequent asthma exacerbation. C1 Massachusetts Gen Hosp, EMNet Coordinating Ctr, Boston, MA 02114 USA. AstraZeneca LP, Hlth Econ & Outcomes Res, Wilmington, DE USA. Hlth Benchmarks Inc, Woodland Hills, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, 326 cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 38 TC 28 Z9 29 U1 1 U2 4 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 15 PY 2007 VL 64 IS 10 BP 1054 EP 1061 DI 10.2146/ajhp060256 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169NS UT WOS:000246599500012 PM 17494905 ER PT J AU Kinane, TB AF Kinane, T. Bernard TI Lung development and implications for hypoplasia found in congenital diaphragmatic hernia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE congenital diaphragmatic hernia (CDH); pulmonary hypoplasia; branching; lung development ID GROWTH-FACTOR RECEPTORS; DEVELOPING MOUSE LUNG; BRANCHING MORPHOGENESIS; SIGNALING PATHWAY; SONIC HEDGEHOG; TRACHEAL SYSTEM; MUTANT MICE; MAP KINASE; EXPRESSION; DROSOPHILA AB Congenital diaphragmatic hernia (CDH) is associated with various degrees of pulmonary hypoplasia and severe persistent pulmonary hypertension in the newborn. These conditions have significant implications for the outcome for the patient. Defects in early lung development are likely to be central to the generation of hypoplasia. A number of mouse models with defects in pathways that are central to lung development were found to have CDH. Understanding all aspects of early lung development will provide fresh insight into the pathogenesis of CDH and its associated conditions. (C) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kinane, TB (reprint author), Massachusetts Gen Hosp, 55 Gruit St,GRJ 1414, Boston, MA 02114 USA. EM tkinane@partners.org NR 86 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD MAY 15 PY 2007 VL 145C IS 2 BP 117 EP 124 DI 10.1002/ajmg.c.30124 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 165FE UT WOS:000246288700003 PM 17436303 ER PT J AU Kling, DE Schnitzer, JJ AF Kling, David E. Schnitzer, Jay J. TI Vitamin A deficiency (VAD), teratogenic, and surgical models of congenital diaphragmatic hernia (CDH) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Review DE teratogen; fetal; lung; retinol; retinoic acid ID HERBICIDE 2,4-DICHLOROPHENYL-PARA-NITROPHENYL ETHER; RETINOIC ACID RECEPTORS; HYPOPLASTIC LUNG GROWTH; FETAL PULMONARY ACINUS; EHLERS-DANLOS-SYNDROME; RAR DOUBLE MUTANTS; ANIMAL-MODEL; LAMB MODEL; DIFFERENTIAL EXPRESSION; MORPHOMETRIC-ANALYSIS AB Congenital diaphragmatic hernia (CDH) is a congenital malformation that occurs with a frequency of 0.08 to 0.45 per 1,000 births. Children with CDH are born with the abdominal contents herniated through the diaphragm and exhibit an associated pulmonary hypoplasia which is frequently accompanied by severe morbidity and mortality. Although the etiology of CDH is largely unknown, considerable progress has been made in understanding its molecular mechanisms through the usage of genetic, teratogenic, and surgical models. The following review focuses on the teratogenic and surgical models of CDH and the possible molecular mechanisms of nitrofen (a diphenyl ether, formerly used as an herbicide) in both induction of CDH and pulmonary hypoplasia. In addition, the mechanisms of other compounds including several anti-inflammatory agents that have been linked to CDH will be discussed. Furthermore, this review will also explore the importance of vitamin A in lung and diaphragm development and the possible mechanisms of teratogen interference in vitamin A homeostasis. Continued exploration of these models will bring forth a clearer understanding of CDH and its molecular underpinnings, which will ultimately facilitate development of therapeutic strategies. (C) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Boston Schriners Hosp, Boston, MA USA. RP Kling, DE (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, CPZ6-100,185 Cambridge St, Boston, MA 02114 USA. EM dkling@partners.org NR 171 TC 19 Z9 21 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD MAY 15 PY 2007 VL 145C IS 2 BP 139 EP 157 DI 10.1002/ajmg.c.30129 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA 165FE UT WOS:000246288700005 PM 17436305 ER PT J AU Kantarci, S Donahoe, PK AF Kantarci, Sibel Donahoe, Patricia K. TI Congenital diaphragmatic hernia (CDH) etiology as revealed by pathway genetics SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE congenital diaphragmatic hernia (CDH); genetic pathways; Fryns syndrome; Donnai-Barrow syndrome; homozygosity mapping ID COMPARATIVE GENOMIC HYBRIDIZATION; LUNG DEVELOPMENT; CANDIDATE REGION; SONIC HEDGEHOG; RING CHROMOSOME-15; FRYNS-SYNDROME; DELETION; DEFECTS; MICE; DISEASE AB Congenital diaphragmatic hernia (CDH) is a common birth defect with high mortality and morbidity. Two hundred seventy CDH patients were ascertained, carefully phenotyped, and classified as isolated (diaphragm defects alone) or complex (with additional anomalies) cases. We established different strategies to reveal CDH-critical chromosome loci and genes in humans. Candidate genes for sequencing analyses were selected from CDH animal models, genetic intervals of recurrent chromosomal aberration in humans, such as 15q26.1-q26.2 or 1q41-q42.12, as well as genes in the retinoic acid and related pathways and those known to be involved in embryonic lung development. For instance, FOG2, GATA4, and COUP-TFII are all needed for both normal diaphragm and lung development and are likely all in the same genetic and molecular pathway. Linkage analysis was applied first in a large inbred family and then in four multiplex families with Donnai-Barrow syndrome (DBS) associated with CDH. 10K SNP chip and microsatellite markers revealed a DBS locus on chromosome 2q23.3-q31.1. We applied array-based comparative genomic hybridization (aCGH) techniques to over 30, mostly complex, CDH patients and found a de novo microdeletion in a patient with Fryns syndrome related to CDH. Fluorescence in situ hybridization (FISH) and multiplex ligation-dependent probe amplification (MLPA) techniques allowed us to further define the deletion interval. Our aim is to identify genetic intervals and, in those, to prioritize genes that might reveal molecular pathways, mutations in any step of which, might contribute to the same phenotype. More important, the elucidation of pathways may ultimately provide clues to treatment strategies. (C) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, CPZN N 6 206, Boston, MA 02114 USA. EM pdonahoe@partners.org NR 61 TC 31 Z9 32 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD MAY 15 PY 2007 VL 145C IS 2 BP 217 EP 226 DI 10.1002/ajmg.c.30132 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 165FE UT WOS:000246288700010 PM 17436295 ER PT J AU McClure, MM Barch, DM Romero, MJ Minzenberg, MJ Triebwasser, J Harvey, PD Siever, LJ AF McClure, Margaret M. Barch, Deanna M. Romero, Michelle J. Minzenberg, Michael J. Triebwasser, Joseph Harvey, Philip D. Siever, Larry J. TI The effects of guanfacine on context processing abnormalities in Schizotypal personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE cognition; guanfacine; pharmacology; schizophrenia; Schizotypal; working memory ID SCHIZOPHRENIA; DEFICITS; DYSFUNCTION; COGNITION; DOPAMINE; CORTEX AB Background: The signature of impaired cognition in people with schizotypal personality disorder (SPD) maybe centrally related to working memory impairments. Guanfacine, an alpha(2A) agonist that acts post-synaptically in the prefrontal cortex (PFC), has shown potential for reducing working memory limitations in other populations. This study examined the potential of guanfacine for improving context processing, a feature of working memory, in SPD. Methods: 29 individuals with SPD entered into a 4-week, randomized parallel-design, double-blind, placebo-controlled trial of guanfacine treatment, followed by a 4-week open-label extension. A modified version of the AX-Continuous Performance Test (AX-CPT) was administered. On this task, evidence of intact context processing includes few BX errors (false cue, correct probe) and higher levels of AY errors (correct cue, false probe). Results: At the end of double-blind treatment, participants treated with guanfacine demonstrated a significant reduction in BX errors and a small but significant increase in AY errors, a pattern that was not seen in the participants treated with placebo. Conclusions: SPD participants improved in their context processing toward a normal response bias, making fewer BX and more AY errors, after being treated with guanfacine. C1 Bronx Vet Adm Med Ctr, VA VISN 3 MIRECC, Bronx, NY 10468 USA. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA. James J Peters Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. RP McClure, MM (reprint author), Bronx Vet Adm Med Ctr, VA VISN 3 MIRECC, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM margaret.mcnamara@mssm.edu RI Barch, Deanna/G-8638-2013 FU NCRR NIH HHS [M01-RR-00071]; NIMH NIH HHS [MH 56140, MH 63116] NR 18 TC 22 Z9 23 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 2007 VL 61 IS 10 BP 1157 EP 1160 DI 10.1016/j.biopsych.2006.06.034 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 165VV UT WOS:000246335100007 PM 16950221 ER PT J AU Armand, P Kim, HT Cutler, CS Ho, VT Koreth, J Alyea, EP Soiffer, RJ Antin, JH AF Armand, Philippe Kim, Haesook T. Cutler, Corey S. Ho, Vincent T. Koreth, John Alyea, Edwin P. Soiffer, Robert J. Antin, Joseph H. TI Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; IRON-CHELATION-THERAPY; LONG-TERM SURVIVORS; RISK-FACTOR; THALASSEMIA; OVERLOAD; HEMOCHROMATOSIS; LEUKEMIA; DISEASE AB Iron overload could be a significant contributor to treatment-related mortality (TRM) for patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). We studied 590 patients who underwent myeloablative allogeneic HSCT at our institution, and on whom a pretransplantation serum ferritin was available. An elevated pretransplantation serum ferritin level was strongly associated with lower overall and disease-free survival. Subgroup multivariable analyses demonstrated that this association was restricted to patients with acute leukemia or myelodysplastic syndrome (MDS); in the latter group, the inferior survival was attributable to a significant increase in TRM. There was also a trend toward an increased risk of veno-occlusive disease in patients with high ferritin. Our results argue that iron overload plays an important role in transplantation outcome for patients with acute leukemia or MDS, as it does in thalassemia. They also suggest future prospective trials to examine the potential benefit of chelation therapy in this setting. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM parmand@partners.org FU NCI NIH HHS [T32 CA009172]; NHLBI NIH HHS [P01 HL070 149] NR 18 TC 255 Z9 268 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 2007 VL 109 IS 10 BP 4586 EP 4588 DI 10.1182/blood-2006-10-054924 PG 3 WC Hematology SC Hematology GA 169RJ UT WOS:000246609100071 PM 17234738 ER PT J AU D'Amico, AV Denham, JW Bolla, M Collette, L Lamb, DS Tai, KH Steigler, A Chen, MH AF D'Amico, Anthony V. Denham, James W. Bolla, Michel Collette, Laurence Lamb, David S. Tai, Keen-Hun Steigler, Allison Chen, Ming-Hui TI Short- vs long-term androgen suppression plus external beam radiation therapy and survival in men of advanced age with node-negative high-risk adenocarcinoma of the prostate SO CANCER LA English DT Article DE prostate cancer; androgen suppression therapy; survival ID RANDOMIZED CONTROLLED-TRIAL; DEPRIVATION THERAPY; PHASE-III; SERUM TESTOSTERONE; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; HORMONAL-THERAPY; CANCER; TIME; NORMALIZATION AB BACKGROUND. The study evaluated whether the use of 3 years as compared with 6 months of androgen suppression therapy (AST) combined with external beam radiation therapy (RT) in the treatment of high-risk prostate cancer was associated with prolonged survival in advanced age men. METHODS. A pooled analysis of 311 men enrolled in 3 prospective randomized trials between 1987 and 2000 who received 6 months or 3 years of AST and RT for locally advanced or high-grade localized adenocarcinoma of the prostate comprised the study cohort. Cox regression multivariable analysis was performed adjusting for known prognostic factors to determine whether the treatment received was associated with time to death after randomization. The median age and follow-up was 70 and 5.9 years, respectively, during which 82 (26%) deaths occurred. RESULTS. Treatment received was not significantly associated with survival time after randomization (adjusted hazard ratio [AHR]: 1.1; 95% confidence interval [CI]: 0.7, 1.8; P = .70), whereas age at randomization (AHR: 1.05; 95% CI: 1.01, 1.09; P = .02) was. The presence of Gleason score 8 to 10 cancers approached significance (AHR: 1.6; 95% CI: 0.9, 2.6; P = .09). CONCLUSIONS. After adjusting for known prognostic factors, the treatment of node-negative, high-risk prostate cancer using 3 years as compared with 6 months of AST with RT was not associated with prolonged survival in men of advanced age. The European Organization for Research and Treatment of Cancer randomized trial will help answer whether unknown confounding factors affected the results of the study. Cancer 2007;109:2004-10. (C) 2007 American Cancer Society. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Newcastle Mater Hosp, TransTasman Radiat Oncol Grp, Newcastle, NSW, Australia. Ctr Hosp Reg Grenoble, Dept Radiat Oncol, Grenoble, France. European Org Res Treatment Canc, Ctr Data, Dept Stat, Brussels, Belgium. Wellington Hosp, Dept Radiat Oncol, Wellington, New Zealand. Peter MacCallum Canc Inst, Dept Radiat Oncol, Melbourne, Vic 3000, Australia. 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@lroc.harvard.edu RI DENHAM, JAMES/G-7505-2013 OI DENHAM, JAMES/0000-0002-4177-9503 NR 31 TC 24 Z9 26 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 2007 VL 109 IS 10 BP 2004 EP 2010 DI 10.1002/cncr.22628 PG 7 WC Oncology SC Oncology GA 164RX UT WOS:000246252800011 PM 17397033 ER PT J AU Ramsey, MR Krishnamurthy, J Pei, XH Torrice, C Lin, WL Carrasco, DR Ligon, KL Xiong, Y Sharpless, NE AF Ramsey, Matthew R. Krishnamurthy, Janakiraman Pei, Xin-Hai Torrice, Chad Lin, Weili Carrasco, Daniel R. Ligon, Keith L. Xiong, Yue Sharpless, Norman E. TI Expression of p16(Ink4a) compensates for p18(Ink4c) loss in cyclin-dependent kinase 4/6-dependent tumors and tissues SO CANCER RESEARCH LA English DT Article ID CELL-CYCLE; INHIBITORS P18(INK4C); INK4 FAMILY; MICE; TUMORIGENESIS; CDK4; SUPPRESSOR; GENE; P19(INK4D); SENESCENCE AB Cell cycle progression from G(1) to S phase depends on phosphorylation of pRb by complexes containing a cyclin (D type or E type) and cyclin-dependent kinase (e.g., cdk2, cdk4, or cdk6). Ink4 proteins function to oppose the action of cdk4/6-cyclin D complexes by inhibiting cdk4/6. We employed genetic and pharmacologic approaches to study the interplay among Ink4 proteins and cdk4/6 activity in vivo. Mouse embryo fibroblasts (MEF) lacking p16(Ink4a) and p18(Ink4c) showed similar growth kinetics as wild-type MEFs despite increased cdk4 activity. In vivo, germline deficiency of p16(Ink4a) and p18(Ink4c) resulted in increased proliferation in the intermediate pituitary and pancreatic islets of adult mice, and survival of p16(Ink4a-/-);p18(Ink4c-/-) mice was significantly reduced due to aggressive pituitary tumors. Compensation among the Ink4 proteins was observed both in vivo in p18(Ink4c-/-) mice and in MEFs from p16(Ink4a-/-), p18(Ink4c-/-), or p16(Ink4a-/-);p18(Ink4c-/-) mice. Treatment with PD 0332991, a specific cdk4/6 kinase inhibitor, abrogated proliferation in those compartments where Ink4 deficiency was associated with enhanced proliferation (i.e., islets, pituitary, and B lymphocytes) but had no effect on proliferation in other tissues such as the small bowel. These data suggest that p16(Ink4a) and p18(Ink4c) coordinately regulate the in vivo catalytic activity of cdk4/6 in specific compartments of adult mice. C1 Univ N Carolina, Sch Med, Dept Med & Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Neurol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Curriculum Genet & Mol Biol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sharpless, NE (reprint author), Univ N Carolina, Sch Med, Dept Med & Genet, Lineberger Comprehens Canc Ctr, CB 7295, Chapel Hill, NC 27599 USA. EM nes@med.une.edu RI Pei, Xin-Hai/P-1812-2014; OI Ramsey, Matthew/0000-0003-2402-8502 FU NIA NIH HHS [AG024379]; NIDDK NIH HHS [DK34987]; NIGMS NIH HHS [GM008581] NR 48 TC 41 Z9 41 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2007 VL 67 IS 10 BP 4732 EP 4741 DI 10.1158/0008-5472.CAN-06-3437 PG 10 WC Oncology SC Oncology GA 172BG UT WOS:000246778500023 PM 17510401 ER PT J AU van Vlerken, LE Duan, ZF Seiden, MV Amiji, MM AF van Vlerken, Lilian E. Duan, Zhenfeng Seiden, Michael V. Amiji, Mansoor M. TI Modulation of intracellular ceramide using polymeric nanoparticles to overcome multidrug resistance in cancer SO CANCER RESEARCH LA English DT Article ID TUMOR-TARGETED DELIVERY; APOPTOTIC CELL-DEATH; POLY(EPSILON-CAPROLACTONE) NANOPARTICLES; CARCINOMA-CELLS; BREAST-CANCER; GLUCOSYLCERAMIDE; TAMOXIFEN; GLYCOSYLATION; SPHINGOLIPIDS; DEGRADATION AB Although multidrug resistance (MDR) is known to develop through a variety of molecular mechanisms within the tumor cell, many tend to converge toward the alteration of apoptotic signaling. The enzyme glucosylceramide synthase (GCS), responsible for bioactivation of the proapoptotic mediator ceramide to a nonfunctional moiety glucosylceramide, is overexpressed in many MDR tumor types and has been implicated in cell survival in the presence of chemotherapy. The purpose of this study was to investigate the therapeutic strategy of coadministering ceramide with paclitaxel, a commonly used chemotherapeutic agent, in an attempt to restore apoptotic signaling and overcome MDR in the human ovarian cancer cell line SKOV3. Poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticles were used to encapsulate and deliver the therapeutic agents for enhanced efficacy. Results show that indeed the cotherapy eradicates the complete population of MDR cancer cells when they are treated at their IC50 dose of paclitaxel. More interestingly, when the cotherapy was combined with the properties of nanoparticle drug delivery, the MDR cells can he resensitized to a dose of paclitaxel near the IC50 of non-MDR (drug sensitive) cells, indicating a 100-fold increase in chemosensitization via this approach. Molecular analysis of activity verified the hypothesis that the efficacy of this therapeutic approach is indeed due to a restoration in apoptotic signaling, although the beneficial properties of PEO-PCL nanoparticle delivery seemed to enhance the therapeutic success even further, showing the promising potential for the clinical use of this therapeutic strategy to overcome MDR. C1 Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. RP Amiji, MM (reprint author), 110 Mugar Life Sci Bldg,360 Huntington Ave, Boston, MA 02115 USA. EM m.amiji@neu.edu RI Amiji, Mansoor/A-4365-2014 OI Amiji, Mansoor/0000-0001-6170-881X FU NCI NIH HHS [CA-095522, CA-119617] NR 39 TC 119 Z9 122 U1 5 U2 28 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 MAY 15 PY 2007 VL 67 IS 10 BP 4843 EP 4850 DI 10.1158/0008-5472.CAN-06-1648 PG 8 WC Oncology SC Oncology GA 172BG UT WOS:000246778500036 PM 17510414 ER PT J AU Ji, HB Wang, ZX Perera, SA Li, DA Liang, MC Zaghlul, S McNamara, K Chen, L Albert, M Sun, YP Al-Hashem, R Chirieac, LR Padera, R Bronson, RT Thomas, RK Garraway, LA Janne, PA Johnson, BE Chin, L Wong, KK AF Ji, Hongbin Wang, Zhenxiong Perera, Samanthi A. Li, Danan Liang, Mei-Chih Zaghlul, Sara McNamara, Kate Chen, Liang Albert, Mitchell Sun, Yanping Al-Hashem, Ruqayyah Chirieac, Lucian R. Padera, Robert Bronson, Roderick T. Thomas, Roman K. Garraway, Levi A. Janne, Pasi A. Johnson, Bruce E. Chin, Lynda Wong, Kwok-Kin TI Mutations in BRAF and KRAS converge on activation of the mitogen-activated protein kinase pathway in lung cancer mouse models SO CANCER RESEARCH LA English DT Article ID ORAL MEK INHIBITOR; IN-VIVO; K-RAS; C-RAF; CI-1040; MICE; SENSITIVITY; GROWTH; ADENOCARCINOMAS; TUMORIGENESIS AB Mutations in the BRAF and KRAS genes occur in similar to 1% to 2% and 20% to 30% of non-small-cell lung cancer patients, respectively, suggesting that the mitogen-activated protein kinase (MAPK) pathway is preferentially activated in lung cancers. Here, we show that lung-specific expression of the BRAF V600E mutant induces the activation of extracellular signal-regulated kinase (ERK)-1/2 (MAPK) pathway and the development of lung adenocarcinoma with bronchioloalveolar carcinoma features in vivo. Deinduction of transgene expression led to dramatic tumor regression, paralleled by dramatic dephosphorylation of ERK1/2, implying a dependency of BRAF-mutant lung tumors on the MAPK pathway. Accordingly, in vivo pharmacologic inhibition of MAPK/ERK kinase (MEK; MAPKK) using a specific MEK inhibitor, CI-1040, induced tumor regression associated with inhibition of cell proliferation and induction of apoptosis in these de novo lung tumors. CI-1040 treatment also led to dramatic tumor shrinkage in murine lung tumors driven by a mutant KRas allele. Thus, somatic mutations in different signaling intermediates of the same pathway induce exquisite dependency on a shared downstream effector. These results unveil a potential common vulnerability of BRA-F and KRas mutant lung tumors that potentially affects rational deployment of MEK targeted therapies to non-small-cell lung cancer patients. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Ludwig Ctr Canc Res Dana Farber, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Broad Inst MIT & Harvard, Cambridge, MA USA. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D810, Boston, MA 02115 USA. EM kwong1@partners.org OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [CA122794, CA90679]; NIA NIH HHS [AG024379, AG2400401] NR 20 TC 105 Z9 110 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 2007 VL 67 IS 10 BP 4933 EP 4939 DI 10.1158/0008-5472.CAN-06-4592 PG 7 WC Oncology SC Oncology GA 172BG UT WOS:000246778500046 PM 17510423 ER PT J AU Mostaghel, EA Page, ST Lin, DW Fazli, L Coleman, IM True, LD Knudsen, B Hess, DL Nelson, CC Matsumoto, AM Bremner, WJ Gleave, ME Nelson, PS AF Mostaghel, Elahe A. Page, Stephanie T. Lin, Daniel W. Fazli, Ladan Coleman, Ilsa M. True, Lawrence D. Knudsen, Beatrice Hess, David L. Nelson, Colleen C. Matsumoto, Alvin M. Bremner, Witham J. Gleave, Martin E. Nelson, Peter S. TI Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: Therapeutic implications for castration-resistant prostate cancer SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; DEPRIVATION THERAPY; HORMONAL-THERAPY; RESPONSIVE GENES; RECEPTOR; TISSUE; PROGRESSION; CELLS; ANTIANDROGENS; MICROARRAYS AB Androgen deprivation therapy (ADT) remains the primary treatment for advanced prostate cancer. The efficacy of ADT has not been rigorously evaluated by demonstrating suppression of prostatic androgen activity at the target tissue and molecular level. We determined the efficacy and consistency of medical castration in suppressing prostatic androgen levels and androgen-regulated gene expression. Androgen levels and androgen-regulated gene expression (by microarray profiling, quantitative reverse transcription-PCR, and immunohistochemistry) were measured in prostate samples from a clinical trial of short-term castration (1 month) using the gonadotropin-releasing hormone antagonist, Acyline, versus placebo in healthy men. To assess the effects of long-term ADT, gene expression measurements were evaluated at baseline and after 3, 6, and 9 months of neoadjuvant ADT in prostatectomy samples from men with localized prostate cancer. Medical castration reduced tissue androgens by 75% and reduced the expression of several androgen-regulated genes (NDRG1, FKBP5, and TMPRSS2). However, many androgen-responsive genes, including the androgen receptor (A-R) and prostate-specific antigen (PSA), were not suppressed after short-term castration or after 9 months of neoadjuvant ADT. Significant heterogeneity in PSA and AR protein expression was observed in prostate cancer samples at each time point of ADT. Medical castration based on serum testosterone levels cannot be equated with androgen ablation in the prostate microenvironment. Standard androgen deprivation does not consistently suppress androgen-dependent gene expression. Suboptimal suppression of tumoral androgen activity may lead to adaptive cellular changes allowing prostate cancer cell survival in a low androgen environment. Optimal clinical efficacy will require testing of novel approaches targeting complete suppression of systemic and intracrine contributions to the prostatic androgen microenvironment. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Vancouver Gen Hosp, Vancouver, BC, Canada. Oregon Natl Primate Res Ctr, Beaverton, OR USA. RP Nelson, PS (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,MS D4-100, Seattle, WA 98109 USA. EM pnelson@fhcrc.org FU NCI NIH HHS [K23 CA122820-01, P50CA97186, T32 CA09515-21]; NCRR NIH HHS [RR0163]; NIA NIH HHS [K23AG027238-01A1, K23 AG027238, K23 AG027238-01A1]; NICHD NIH HHS [U54 HD42454]; NIDDK NIH HHS [DK65083, DK65204] NR 49 TC 297 Z9 302 U1 0 U2 9 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 MAY 15 PY 2007 VL 67 IS 10 BP 5033 EP 5041 DI 10.1158/0008-5472.CAN-06-3332 PG 9 WC Oncology SC Oncology GA 172BG UT WOS:000246778500059 PM 17510436 ER PT J AU Behler, CM Vittinghoff, E Lin, F Chung, RT Peters, MG Robbins, GK Volberding, PA AF Behler, Caroline M. Vittinghoff, Eric Lin, Feng Chung, Raymond T. Peters, Marion G. Robbins, Gregory K. Volberding, Paul A. TI Hematologic toxicity associated with interferon-based hepatitis C therapy in HIV type 1-coinfected subjects SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; HCV-INFECTED PATIENTS; INJECTION-DRUG USERS; COMBINATION THERAPY; SUSTAINED RESPONSE; INITIAL TREATMENT; GROWTH-FACTORS; LIVER-DISEASE; COINFECTION AB Background. This study investigates whether dose modifications for adverse hematologic effects or the use of hematopoietic growth factors influenced the outcome of therapy for hepatitis C virus (HCV) infection in patients who were coinfected with HCV and human immunodeficiency virus (HIV) and who were participants in a randomized, controlled trial. Methods. Subjects were randomized to receive ribavirin plus interferon-alfa-2a (IFN-alfa-2a) or pegylated IFN-alfa-2a for a total of 48 weeks. Doses were modified for a number of adverse effects ( including hematologic toxicity), and hematopoietic growth factors were administered at the discretion of the physician. Associations of dose modifications or initiation of hematopoietic growth factor support with treatment outcomes were determined by standard statistical methods. Results. One hundred thirty-three subjects were included in this study. Subjects treated with pegylated IFN-alfa-2a were more likely to have had dose modifications (dose reduction or discontinuation) than were those treated with IFN-alfa-2a. By multivariate analysis, treatment with pegylated IFN-alfa-2a is associated with higher sustained virologic and/or histologic response. Dose modifications for nonhematologic toxicity are independently associated with lower sustained virologic and/ or histologic responses. Although hematologic toxicity was not directly associated with clinical outcome in this analysis, use of hematopoietic growth factors was associated with an increased sustained virologic and/ or histologic response. Conclusions. Dose modifications for anti-HCV therapy may adversely affect the outcome of treatment of HCV in individuals who are coinfected with HIV. The use of hematopoietic growth factor support may be associated with an improved clinical response to therapy. C1 Univ Calif San Francisco, Dept Hematol & Oncol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Gastroenterol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Vet Adm Med Ctr, Dept Infect Dis, San Francisco, CA 94121 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Behler, CM (reprint author), Univ Calif San Francisco, Dept Hematol & Oncol, 505 Parnassus Ave,M1286,Box 1270, San Francisco, CA 94143 USA. EM caroline.behler@ucsf.edu FU NIAID NIH HHS [P30 AI027763, U01 AI27663, U01 AI069502, P30 AI27763, U01 AI027663] NR 37 TC 13 Z9 13 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2007 VL 44 IS 10 BP 1375 EP 1383 DI 10.1086/515398 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 158HD UT WOS:000245781500019 PM 17443478 ER PT J AU Watanabe, S Nagano, S Duce, J Kiaei, M Li, QX Tucker, SM Tiwari, A Brown, RH Beal, MF Hayward, LJ Culotta, VC Yoshihara, S Sakoda, S Bush, AI AF Watanabe, Shohei Nagano, Seiichi Duce, James Kiaei, Mahmoud Li, Qiao-Xin Tucker, Stephanie M. Tiwari, Ashutosh Brown, Robert H., Jr. Beal, M. Flint Hayward, Lawrence J. Culotta, Valeria C. Yoshihara, Satoshi Sakoda, Saburo Bush, Ashley I. TI Increased affinity for copper mediated by cysteine 111 in forms of mutant superoxide dismutase 1 linked to amyotrophic lateral sclerosis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE amyotrophic lateral sclerosis; Cu,Zn-superoxide dismutase; copper; immobilized metal affinity chromatography; Cu chaperone for SOD1; cysteine; protein stability; oxidative stress; free radicals ID ZINC SUPEROXIDE-DISMUTASE; MOTOR-NEURON DEGENERATION; BINDING-SITE; CONFORMATIONAL STABILITY; PROTEIN-BINDING; TRANSGENIC MICE; MODEL MICE; DISEASE; SOD1; ALS AB Mutations in Cu,Zn-superoxide dismutase (SODI) cause familial amyotrophic lateral sclerosis (ALS). It has been proposed that neuronal cell death might occur due to inappropriately increased Cu interaction with mutant SODI. Using Cu immobilized metal-affinity chromatography (IMAC), we showed that mutant SOD1 (A4V, G85R, and G93A) expressed in transfected COS7 cells, transgenic mouse spinal cord tissue, and transformed yeast possessed higher affinity for Cu than wild-type SOD1. Serine substitution for cysteine at the Cyst 111 residue in mutant SODI abolished the Cu interaction on IMAC. C111S substitution reversed the accelerated degradation of mutant SOD1 in transfected cells, suggesting that the Cyst 111 residue is critical for the stability of mutant SOD1. Aberrant Cu binding at the Cys 111 residue may be a significant factor in altering mutant SOD1 behavior and may explain the benefit of controlling Cu access to mutant SODI in models of familial ALS. (c) 2007 Elsevier Inc. All rights reserved. C1 Osaka Univ, Grad Sch Med, Dept Neurol, Suita, Osaka 5650871, Japan. Univ Melbourne, Oxidat Disorders Lab, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Osaka Univ, Grad Sch Med, Dept Mol Med, Suita, Osaka 5650871, Japan. RP Nagano, S (reprint author), Osaka Univ, Grad Sch Med, Dept Neurol, Suita, Osaka 5650871, Japan. EM abush@mhri.edu.au RI Tiwari, Ashutosh/A-7458-2008; Bush, Ashley/A-1186-2007 OI Tiwari, Ashutosh/0000-0001-7373-349X; Bush, Ashley/0000-0001-8259-9069 FU NIGMS NIH HHS [GM 50016]; NINDS NIH HHS [R01 NS044170] NR 51 TC 28 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 15 PY 2007 VL 42 IS 10 BP 1534 EP 1542 DI 10.1016/j.freradbiomed.2007.02.004 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 163MR UT WOS:000246164500009 PM 17448900 ER PT J AU Liu, HF Schmidt-Supprian, M Shi, YJ Hobeika, E Barteneva, N Jumaa, H Pelanda, R Reth, M Skok, J Rajewsky, K Shi, Y AF Liu, Huifei Schmidt-Supprian, Marc Shi, Yujiang Hobeika, Elias Barteneva, Natasha Jumaa, Hassan Pelanda, Roberta Reth, Michael Skok, Jane Rajewsky, Klaus Shi, Yang TI Yin Yang 1 is a critical regulator of B-cell development SO GENES & DEVELOPMENT LA English DT Article DE YY1; immunoglobulin gene; B-cell development; V(D)J recombination ID HEAVY-CHAIN GENE; TRANSCRIPTION FACTOR YY1; IGH INTRONIC ENHANCER; DNA-BINDING PROTEIN; POLYCOMB GROUP GENE; TRANSGENIC SUBSTRATE; V(D)J RECOMBINATION; PRO-B; LOCUS; RECEPTOR AB The role of the transcription factor Yin Yang 1 (YY1) in development is largely unknown. Here we show that specific ablation of YY1 in mouse B cells caused a defect in somatic rearrangement in the immunoglobulin heavy-chain (IgH) locus and a block in the progenitor-B-to-precursor-B-cell transition, which was partially rescued by a prerearranged IgH transgene. Three-dimensional DNA fluorescence in situ hybridization analysis revealed an important function for YY1 in IgH locus contraction, a process indispensable for distal V(H) to D(H)J(H) recombination. We provide evidence that YY1 binds the intronic Ei mu enhancer within the IgH locus, consistent with a direct role for YY1 in V(H)D(H)J(H) recombination. These findings identified YY1 as a critical regulator of early B-cell development. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Max Planck Inst Immunobiol, D-79108 Freiburg, Germany. Univ Freiburg, Inst Biol 3, D-79108 Freiburg, Germany. CBR Inst Biomed Res Inc, Flow Cytometry Core Facil, Boston, MA 02115 USA. UCL, Div Infect & Immun, Dept Immunol & Mol Pathol, London W1T 4JF, England. RP Shi, Y (reprint author), NYU, Sch Med, Dept Pathol, 550 1St Ave, New York, NY 10016 USA. EM yang_shi@hms.harvard.edu RI Schmidt-Supprian, Marc/F-5893-2011; OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Skok, Jane/0000-0002-4145-1516 FU NIAID NIH HHS [AI057947, R01 AI057947]; NIGMS NIH HHS [GM53874, R01 GM053874]; Wellcome Trust NR 60 TC 127 Z9 131 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 2007 VL 21 IS 10 BP 1179 EP 1189 DI 10.1101/gad.1529307 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 168NR UT WOS:000246531800007 PM 17504937 ER PT J AU Allen, BL Tenzen, T McMahon, AP AF Allen, Benjamin L. Tenzen, Toyoaki McMahon, Andrew P. TI The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development SO GENES & DEVELOPMENT LA English DT Article DE mouse; Hedgehog; neural tube; development; Gas1; Cdo ID ARREST-SPECIFIC GENE-1; PROGENITOR-CELL IDENTITY; CENTRAL-NERVOUS-SYSTEM; VENTRAL NEURAL-TUBE; SONIC-HEDGEHOG; FLOOR PLATE; NEURONAL FATE; SPINAL-CORD; GROWTH; MICE AB Hedgehog (Hh) signaling is critical for patterning and growth during mammalian embryogenesis. Transcriptional profiling identified Growth-arrest-specific 1 (Gas1) as a general negative target of Shh signaling. Data presented here define Gas1 as a novel positive component of the Shh signaling cascade. Removal of Gas1 results in a Shh dose- dependent loss of cell identities in the ventral neural tube and facial and skeletal defects, also consistent with reduced Shh signaling. In contrast, ectopic Gas1 expression results in Shh- dependent cell-autonomous promotion of ventral cell identities. These properties mirror those of Cdo, an unrelated, cell surface Shh-binding protein. We show that Gas1 and Cdo cooperate to promote Shh signaling during neural tube patterning, craniofacial, and vertebral development. Overall, these data support a new paradigm in Shh signaling whereby positively acting ligand- binding components, which are initially expressed in responding tissues to promote signaling, are then down- regulated by active Hh signaling, thereby modulating responses to ligand input. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP McMahon, AP (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM mcmahon@mcb.harvard.edu FU NINDS NIH HHS [R37 NS033642] NR 65 TC 138 Z9 143 U1 0 U2 1 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 MAY 15 PY 2007 VL 21 IS 10 BP 1244 EP 1257 DI 10.1101/gad.1543607 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 168NR UT WOS:000246531800012 PM 17504941 ER PT J AU Shelbourne, PF Keller-McGandy, C Bi, WL Yoon, SR Dubeau, L Veitch, NJ Vonsattel, JP Wexler, NS Arnheim, N Augood, SJ AF Shelbourne, Peggy F. Keller-McGandy, Christine Bi, Wenya Linda Yoon, Song-Ro Dubeau, Louis Veitch, Nicola J. Vonsattel, Jean Paul Wexler, Nancy S. Arnheim, Norman Augood, Sarah J. CA US Venezuela Collaborative Res Grp TI Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain SO HUMAN MOLECULAR GENETICS LA English DT Article ID PALLIDOLUYSIAN ATROPHY DRPLA; CAG-REPEAT; SOMATIC MOSAICISM; TRINUCLEOTIDE REPEAT; MUTANT HUNTINGTIN; EXPANSION; NEURONS; INSTABILITY; GENE; MICRODISSECTION AB Huntington disease is caused by the expansion of a CAG repeat encoding an extended glutamine tract in a protein called huntingtin. Here, we provide evidence supporting the hypothesis that somatic increases of mutation length play a role in the progressive nature and cell-selective aspects of HD pathogenesis. Results from micro-dissected tissue and individual laser-dissected cells obtained from human HID cases and knock-in HD mice indicate that the CAG repeat is unstable in all cell types tested although neurons tend to have longer mutation length gains than glia. Mutation length gains occur early in the disease process and continue to accumulate as the disease progresses. In keeping with observed patterns of cell loss, neuronal mutation length gains tend to be more prominent in the striatum than in the cortex of low-grade human HD cases, less so in more advanced cases. Interestingly, neuronal sub-populations of HD mice appear to have different propensities for mutation length gains; in particular, smaller mutation length gains occur in nitric oxide synthase-positive striatal interneurons (a relatively spared cell type in HD) compared with the pan-striatal neuronal population. More generally, the data demonstrate that neuronal changes in HD repeat length can be at least as great, if not greater, than those observed in the germline. The fact that significant CAG repeat length gains occur in non-replicating cells also argues that processes such as inappropriate mismatch repair rather than DNA replication are involved in generating mutation instability in HD brain tissue. C1 Univ So Calif, Program Mol & Computat Biol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. Univ Glasgow, Div Mol Genet, Glasgow G11 6NU, Lanark, Scotland. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Mass Gen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, New York Brain Bank, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Neurol & Psychiat, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Herediatary Dis Fdn, New York, NY 10032 USA. RP Arnheim, N (reprint author), Univ So Calif, Program Mol & Computat Biol, Los Angeles, CA 90089 USA. EM arnheim@usc.edu FU NIGMS NIH HHS [GM36745, R01 GM036745, R01 GM036745-21] NR 33 TC 69 Z9 70 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 15 PY 2007 VL 16 IS 10 BP 1133 EP 1142 DI 10.1093/hmg/ddm054 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 182VC UT WOS:000247531100001 PM 17409200 ER PT J AU Mihai, S Chiriac, MT Takahashi, K Thurman, JM Holers, VM Zillikens, D Botto, M Sitaru, C AF Mihai, Sidonia Chiriac, Mircea T. Takahashi, Kazue Thurman, Joshua M. Holers, V. Michael Zillikens, Detlef Botto, Marina Sitaru, Cassian TI The alternative pathway of complement activation is critical for blister induction in experimental epidermolysis bullosa acquisita SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DERMAL-EPIDERMAL SEPARATION; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; COLLAGEN-INDUCED ARTHRITIS; VII COLLAGEN; PASSIVE TRANSFER; FACTOR-B; AUTOANTIBODIES; MICE; NEUTROPHILS; C5A AB Epidermolysis bullosa acquisita is a subepidermal blistering disease associated with tissue-bound and circulating autoantibodies against type VII collagen, a major constituent of the dermal-epidermal junction. The passive transfer of Abs against type VII collagen into mice induces a subepidermal blistering disease dependent upon activation of terminal complement components. To further dissect the role of the different complement activation pathways in this model, we injected C1qdeficient, mannan-binding lectin-deficient, and factor B-deficient mice with rabbit Abs against murine type VII collagen. The development and evolution of blistering had a similar pattern in mannan-binding lectin-deficient and control mice and was initially only marginally less extensive in Clq-deficient mice compared with controls. Importantly, factor B-deficient mice developed a delayed and significantly less severe blistering disease compared with factor B-sufficient mice. A significantly lower neutrophilic infiltration was observed in factor B-deficient mice compared with controls and local reconstitution with granulocytes restored the blistering disease in factor B-deficient mice. Our study provides the first direct evidence for the involvement of the alternative Pathway in an autoantibody-induced blistering disease and should facilitate the development of new therapeutic strategies for epidermolysis bullosa acquisita and related autoimmune diseases. The Journal of Immunology, 2007, 178: 6514-6521. C1 Med Univ Lubeck, Dept Dermatol, D-23538 Lubeck, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Dev Immunol,Dept Pediat, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80218 USA. Imperial Coll Sch Med, Rheumatol Sect, London, England. RP Sitaru, C (reprint author), Med Univ Lubeck, Dept Dermatol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM csitaru@fastmail.fm RI Sitaru, Cassian/E-5830-2010; Zillikens, Detlef/C-8572-2011 OI Sitaru, Cassian/0000-0002-0370-1270; FU NIAID NIH HHS [R01 AI-31105]; NIDDK NIH HHS [K08 DK64790] NR 47 TC 46 Z9 45 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2007 VL 178 IS 10 BP 6514 EP 6521 PG 8 WC Immunology SC Immunology GA 165EG UT WOS:000246286200059 PM 17475881 ER PT J AU Kitamura, M Iwabuchi, K Kitaichi, N Kon, S Kitamei, H Namba, K Yoshida, K Denhardt, DT Rittling, SR Ohno, S Uede, T Onoe, K AF Kitamura, Mizuki Iwabuchi, Kazuya Kitaichi, Nobuyoshi Kon, Shigeyuki Kitamei, Hirokuni Namba, Kenichi Yoshida, Kazuhiko Denhardt, David T. Rittling, Susan R. Ohno, Shigeaki Uede, Toshimitsu Onoe, Kazunori TI Osteopontin aggravates experimental autoimmune uveoretinitis in mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CRYPTIC EPITOPE SLAYGLR; RHEUMATOID-ARTHRITIS; MURINE MODEL; IN-VITRO; T-CELLS; UVEITIS; CYTOKINE; RECEPTOR; PEPTIDE; MIGRATION AB Human endogenous uveitis is a common sight-threatening intraocular inflammatory disease and has been studied extensively using a murine model of experimental autoimmune uveoretinitis (EAU). It is possibly mediated by Th1 immune responses. In the present study, we investigated the role of osteopontin (OPN), a protein with pleiotropic functions that contributes to the development of Th1 cell-mediated immunity. Accompanying EAU progression, OPN was elevated in wild-type (WT) mice that had been immunized with human interphotoreceptor retinoid-binding protein (hIRBP) peptide 1-20. OPN-deficient (OPN-/-) mice showed milder EAU progression in clinical and histopathological scores compared with those of WT mice. The T cells from hIRBPimmunized OPN-/- mice exhibited reduced Ag-specific proliferation and proinflammatory cytokine (TNF-alpha and IFN-,gamma) production compared with those of WT T cells. When hIRBP-immunized WT mice were administered M5 Ab reacting to SLAYGLR sequence, a cryptic binding site to integrins within OPN, EAU development was significantly ameliorated. T cells from hIRBPimmunized WT mice showed significantly reduced proliferative responses and proinflammatory cytokine production upon stimulation with hIRBP peptide in the presence of M5 Ab in the culture. Our present results demonstrate that OPN may represent a novel therapeutic target to control uveoretinitis. The Journal of Immunology, 2007, 178: 6567-6572. C1 Hokkaido Univ, Inst Med Genet, Div Immunobiol, Kita Ku, Sapporo, Hokkaido 0600815, Japan. Hokkaido Univ, Dept Ophthalmol & Visual Sci, Grad Sch Med, Sapporo, Hokkaido, Japan. Hokkaido Univ, Inst Med Genet, Div Mol Immunol, Sapporo, Hokkaido, Japan. Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA. Forsyth Inst, Boston, MA 02115 USA. RP Onoe, K (reprint author), Hokkaido Univ, Inst Med Genet, Div Immunobiol, Kita Ku, Kita 15,Nishi 7, Sapporo, Hokkaido 0600815, Japan. EM kazunori@igm.hokudai.ac.jp RI Kon, Shigeyuki/A-3809-2012; uede, toshimitsu/A-4273-2012 NR 50 TC 27 Z9 29 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2007 VL 178 IS 10 BP 6567 EP 6572 PG 6 WC Immunology SC Immunology GA 165EG UT WOS:000246286200065 PM 17475887 ER PT J AU Fan, J Li, Y Levy, RM Fan, JJ Hackam, DJ Vodovotz, Y Yang, H Tracey, KJ Billiar, TR Wilson, MA AF Fan, Jie Li, Yuehua Levy, Ryan M. Fan, Janet J. Hackam, David J. Vodovotz, Yoram Yang, Huan Tracey, Kevin J. Billiar, Timothy R. Wilson, Mark A. TI Hemorrhagic shock induces NAD(P)H oxidase activation in neutrophils: Role of HMGB1-TLR4 signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MOBILITY GROUP BOX-1; TOLL-LIKE RECEPTOR-4; NF-KAPPA-B; MEDIATES HEPATIC-INJURY; END-PRODUCTS RAGE; PROTEIN-KINASE-C; NADPH OXIDASE; CUTTING EDGE; SYSTEMIC INFLAMMATION; LUNG INFLAMMATION AB Hemorrhagic shock/resuscitation (HS/R)-induced generation of reactive oxygen species (ROS) plays an important role in posthemorrhage inflammation and tissue injury. We have recently reported that HS/R-activated neutrophils (PMN), through release of ROS, serve an important signaling function in mediating alveolar macrophage priming and lung inflammation. PMN NAD(P)H oxiclase has been thought to be an important source of ROS following HS/R. TLR4 sits at the interface of microbial and sterile inflammation by mediating responses to both bacterial endotoxin and multiple endogenous ligands, including high-mo bility group box 1 (HMGB1). Recent studies have implicated HMGB1 as an early mediator of inflammation after HS/R and organ ischemia/ reperfusion. In the present study, we tested the hypothesis that HS/R activates NAD(P)H oxidase in PMN through HMGB1/TLR4 signaling. We demonstrated that HS/R induced PMN NAD(P)H oxidase activation, in the form of phosphorylation of p47(phox)subunit of NAD(P)H oxidase, in wild-type mice; this induction was significantly diminished in TLR4-mutant C3H/HeJ mice. HMGB1 levels in lungs, liver, and serum were increased as early as 2 h after HS/R. Neutralizing Ab to HMGB1 prevented HS/R-induced phosphorylation of p47(phox) in PMN. In addition, in vitro stimulation of PMN with recombinant HMGB1 caused TLR4-dependent activation of NAD(P)H oxidase as well as increased ROS production through both MyD88-IRAK4-p38 MAPK and MyD88-IRAK4-Akt signaling pathways. Thus, PMN NAD(P)H oxidase activation, induced by HS/R and as mediated by HMGBI/TLR4 signaling, is an important mechanism responsible for PMN-mediated inflammation and organ injury after hemorrhage. The Journal of Immunology, 2007, 178: 6573-6580. C1 Vet Affairs Pittsburgh Healthcare Syst, Dept Surg, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA. Childrens Hosp Pittsburgh, Div Pediat Surg, Pittsburgh, PA 15213 USA. NYU, Sch Med, N Shore Univ Hosp, Lab Biomed Sci, Manhasset, NY 11030 USA. RP Fan, J (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Dept Surg, CHERP Bldg 25 151C-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM jif7@pitt.edu OI Tracey, Kevin J/0000-0003-1884-6314 FU NHLBI NIH HHS [R01-HL-079669]; NIGMS NIH HHS [P50-GM-53789] NR 62 TC 166 Z9 181 U1 2 U2 13 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2007 VL 178 IS 10 BP 6573 EP 6580 PG 8 WC Immunology SC Immunology GA 165EG UT WOS:000246286200066 PM 17475888 ER PT J AU Alter, G Teigen, N Ahern, R Streeck, H Meier, A Rosenberg, ES Altfeld, M AF Alter, Galit Teigen, Nickolas Ahern, Ryan Streeck, Hendrik Meier, Angela Rosenberg, Eric S. Altfeld, Marcus TI Evolution of innate and adaptive effector cell functions during acute HIV-1 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NATURAL-KILLER-CELLS; IMMUNODEFICIENCY VIRUS-INFECTION; IMMUNE-RESPONSES; NK CELL; TYPE-1 INFECTION; VIREMIA; MACAQUES; PLASMA; AIDS; REPLICATION AB Early events during acute human immunodeficiency virus type 1 (HIV-1) infection are critical in determining the course of disease progression. Cells of the innate and adaptive immune responses are involved in this acute response to infection; however, little is known about the coevolution of innate and adaptive effector cell populations during the initial phase of HIV-1 infection. Here, we have characterized the development of innate natural killer (NK) cell and adaptive HIV-1-specific CD8(+) T cell function during acute HIV-1 infection. Although NK cell populations were significantly expanded during acute infection before HIV-1 seroconversion, HIV-1-specific CD8(+) T cell responses were absent or weak and were inversely correlated with the level of NK cell activity. NK cell activity was directly correlated with the level of viral replication during acute HIV-1 infection and declined rapidly in subjects who initiated highly active antiretroviral therapy, whereas NK cell activity remained elevated in subjects who did not initiate therapy. Yet, reexposure to HIV-1 antigen during treatment discontinuation in chronic infection resulted in a synchronous increase in NK and CD8(+) T cell activity. Overall, these data demonstrate that expansion of the NK cell population precedes the development of adaptive HIV-1-specific CD8(+) T cells during acute infection but that both effector cell subsets respond with similar kinetics during chronic HIV-1 infection. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Charlestown, MA 02129 USA. RP Altfeld, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Rm 6613, Charlestown, MA 02129 USA. EM maltfeld@partners.org FU NIAID NIH HHS [5R01AI67031, 1 P30 AI060354-01] NR 30 TC 86 Z9 88 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 15 PY 2007 VL 195 IS 10 BP 1452 EP 1460 DI 10.1086/513878 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 158HG UT WOS:000245781800010 PM 17436225 ER PT J AU White, D Moore, S Waring, S Cook, K Lai, E AF White, Donna Moore, Suzanne Waring, Stephen Cook, Karon Lai, Eugene TI Identifying incident cases of parkinsonism among veterans using a tertiary medical center SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; secondary; veterans; incidence; vital status; ICD-9 CM ID QUALITY-OF-LIFE; DISEASE; PREVALENCE; PRISONERS; SPAIN; WAR AB To better understand the impact of incident Parkinson's disease (PD) on the Veteran's Health Administration (VHA) and to develop methods applicable to future epidemiological research, we performed a medical record review study at a tertiary referral VHA medical center. Searching the local data base, we identified 782 veterans with diagnostic codes for PD or secondary parkinsonism (SP) between 1998 and 2000. Based on structured medical record review, a movement disorders specialist confirmed diagnoses for incident parkinsonism cases. Among the 782, 191 incident parkinsonism cases were identified (100 PD, 75 SP, and 16 Parkinson's Plus). Incident PD cases were older at diagnosis (74.5 vs. 70.4 yr; P < 0.05) and more likely to be white (81% vs. 62; P < 0.07) than incident SP cases. Diagnostic codes were insufficient to distinguish between incident PD and SP (positive predictive value, 57% and 39%, respectively), and VHA sources failed to identify 21% of confirmed deaths among the incident PD cohort by November 2004. Although the large number of incident cases identified suggests PD is an important cause of disability among elderly VHA users, observed limitations of VHA sources for identifying incident PD cases and determining their vital status should be considered when designing future studies. (C) 2007 Movement Disorder Society. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Dept Epidemiol, Houston, TX USA. Univ Washington, Seattle, WA 98195 USA. RP Lai, E (reprint author), 2002 Holcombe Blvd, Houston, TX 77030 USA. EM elai@bcm.edu NR 29 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY 15 PY 2007 VL 22 IS 7 BP 915 EP 923 DI 10.1002/mds.21353 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 174BU UT WOS:000246917000002 PM 17415798 ER PT J AU Schrag, A Dodel, R Spottke, A Bornschein, B Siebert, U Quinn, NP AF Schrag, Anette Dodel, Richard Spottke, Annika Bornschein, Bernhard Siebert, Uwe Quinn, Niall P. TI Rate of clinical progression in Parkinson's disease. A prospective study SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; progression; UPDRS; scales ID POSITRON-EMISSION-TOMOGRAPHY; BETA-CIT SPECT; DOPAMINE TRANSPORTER; MOTOR IMPAIRMENT; NATURAL-HISTORY; PET; DISABILITY; LEVODOPA; MORTALITY; SYSTEM AB Few prospective data on the clinical progression of Parkinson's disease (PD) in patient groups outside treatment trials in selected patients are available, and controversy exists on the rate of clinical disease progression with advancing disease. In this study, we investigated the rate of clinical progression of PD in a clinic-based sample of 145 patients over 1 year and in a community-based sample of 124 patients over 4 years. Depending on the sample and clinical scale used, mean deterioration of motor and disability scores ranged from 2.4 to 7.4% of the maximum possible score per year, and standard deviations indicated that there was considerable variability of progression rates between individuals. The progression of motor scores decreased with follow-up over 4 years and significantly decreased in more advanced disease stages. Deterioration of disability scores did not differ between disease stages; this may reflect the increasing rate of disease complications, which contribute to increasing disability in addition to motor impairment alone, in more advanced disease. Thus, motor fluctuations, hallucinations, depression, memory problems, and bladder symptoms were all reported more often at follow-up in the community-based sample (all P < 0.01), and dyskinesias, motor fluctuations, falls, and hallucinations were more common and cognitive and depression scores worse in higher disease stages in the clinic-based sample (all P < 0.001). We conclude that progression of motor scores in PD decreases with advancing disease in PD. However, disability continues to deteriorate with advancing disease and with the development of disease complications that are likely to be related to additional extrastriatal pathology. (C) 2007 Movement Disorder Society. C1 UCL, Dept Clin Neurosci, Royal Free Hosp, London NW3 2PF, England. UCL, Dept Motor Neurosci & Movement Disorders, Inst Neurol, London, England. Univ Marburg, Dept Neurol, Marburg, Germany. UMIT Univ Hlth Sci Med Informat & Technol, Hall, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Schrag, A (reprint author), UCL, Dept Clin Neurosci, Royal Free Hosp, London NW3 2PF, England. EM a.schrag@medsch.ucl.ac.uk RI Schrag, Anette/B-4181-2011 OI Schrag, Anette/0000-0002-9872-6680 NR 53 TC 68 Z9 76 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY 15 PY 2007 VL 22 IS 7 BP 938 EP 945 DI 10.1002/mds.21429 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 174BU UT WOS:000246917000005 PM 17415791 ER PT J AU D'Arceuil, H de Crespigny, A AF D'Arceuil, Helen de Crespigny, Alex TI The effects of brain tissue decomposition on diffusion tensor imaging and tractography SO NEUROIMAGE LA English DT Article ID WATER DIFFUSION; MOUSE-BRAIN; PRIMATE BRAIN; ANISOTROPY; NEWBORN; MATTER; WHITE AB There have been numerous high resolution diffusion tensor imaging studies in fixed animal brains, but relatively few studies in human brains. While animal tissues are generally fixed pre-mortem or directly postmortem, this is not possible for human tissue, therefore there is always some delay between death and tissue fixation. The elapsed time between death and tissue fixation, the postmortem interval (PMI), will most likely adversely affect the tissue's diffusion properties. We studied the effects of PMI on the diffusion properties of rodent brain. Eight mice were euthanized and the brains (kept in the skull) were placed in formalin at PMIs of 0, 1, 4 and 14 days. Post fixation they were placed in a solution of GdDTPA and phosphate buffered saline. Brains were scanned with a 3D EPI DTI sequence at 4.7T. DTI data were processed to generate apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps. DTI tractography was also performed. The temporal changes in regional ADC and FA values were analyzed statistically using a one-way ANOVA, followed by individual Student's T-tests. Regional FA and ADC of gray and white matter decreased significantly with time (p < 0.05). DTI tractography showed a decrease in the number and coherence of reconstructed fiber pathways between PV[Is 0 and 14. Elapsed time between death and tissue fixation has a major effect upon the brain's diffusion properties and should be born in mind when interpreting fixed brain DTI. (C)) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, NMR Ctr, Charlestown, MA 02129 USA. RP D'Arceuil, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, NMR Ctr, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM helen@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR014075-06, P41 RR014075-08, 1S10RR016811, P41RR14075, S10 RR016811, S10 RR016811-01, P41 RR014075]; NIBIB NIH HHS [R01 EB000790, EB00790, R01 EB000790-05]; NINDS NIH HHS [R01 NS041285, NS41285, R01 NS041285-01A1, R01 NS041285-04] NR 15 TC 82 Z9 82 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2007 VL 36 IS 1 BP 64 EP 68 DI 10.1016/j.neuroimage.2007.02.039 PG 5 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 168YI UT WOS:000246559500007 PM 17433879 ER PT J AU Cook, DB O'Connor, PJ Lange, G Steffener, J AF Cook, Dane B. O'Connor, Patrick J. Lange, Gudrun Steffener, Jason TI Functional neuroimaging correlates of mental fatigue induced by cognition among chronic fatigue syndrome patients and controls SO NEUROIMAGE LA English DT Article ID VERBAL WORKING-MEMORY; BECK DEPRESSION INVENTORY; VISUAL ANALOG SCALES; HUMAN BRAIN; FMRI; TASK; COMPONENTS; SYSTEM; MRI; EPIDEMIOLOGY AB The neural mechanisms underlying feelings of fatigue are poorly understood. The primary purpose of the study was to use functional magnetic resonance imaging (fMRI) to determine the association between feelings of mental fatigue and blood oxygen level dependent (BOLD) brain responses during a mentally fatiguing cognitive task. Healthy, non-fatigued controls and chronic fatigue syndrome (CFS) patients were included to determine the influence of chronic levels of fatigue on brain responses. We hypothesized that mental fatigue would be significantly related to brain activity during a fatiguing cognitive task but not during either a non-fatiguing motor (finger tapping) or cognitive (auditory monitoring) task. Patients (n = 9) and controls (n = 11) completed a finger tapping task, a simple auditory monitoring task and a challenging working memory task, designed to induce mental fatigue, while undergoing fMRI. Fatigue was measured prior to scanning and following each task during fMRI data collection. Results showed that mental fatigue was significantly related to brain activity during the fatiguing cognitive task but not the finger tapping or simple auditory monitoring tasks. Significant (p <= 50.005) positive relationships were found for cerebellar, temporal, cingulate and frontal regions. A significant (p=0.001) negative relationship was found for the left posterior parietal cortex. CFS participants did not differ from controls for either finger tapping or auditory monitoring tasks, but exhibited significantly greater activity, in several cortical and subcortical regions during the fatiguing cognitive task. Our results suggest an association between subjective feelings of mental fatigue and brain responses during fatiguing cognition. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Wisconsin, Dept Kinesiol, Unit Gym 2, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Vet Affairs, Madison, WI 53706 USA. Univ Georgia, Dept Kinesiol, Athens, GA 30602 USA. New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ 07018 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Radiol, Newark, NJ 07103 USA. Columbia Univ, Cognit Neurosci Div, Taub Inst Res Alzheimers Dis Aging Brain, New York, NY 10032 USA. RP Cook, DB (reprint author), Univ Wisconsin, Dept Kinesiol, Unit Gym 2, 2000 Observ Dr, Madison, WI 53706 USA. EM dcook@education.wisc.edu NR 61 TC 104 Z9 106 U1 10 U2 32 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 15 PY 2007 VL 36 IS 1 BP 108 EP 122 DI 10.1016/j.neuroimage.2007.02.033 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 168YI UT WOS:000246559500011 PM 17408973 ER PT J AU Gjoerup, OV Wu, JP Chandler-Militello, D Williams, GL Zhao, J Schaffhausen, B Jat, PS Roberts, TM AF Gjoerup, Ole V. Wu, Jiaping Chandler-Militello, Devin Williams, Grace L. Zhao, Jean Schaffhausen, Brian Jat, Parmjit S. Roberts, Thomas M. TI Surveillance mechanism linking Bub1 loss to the p53 pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aneuploidy; senescence; simian virus 40 ID LARGE T-ANTIGEN; SV40 LARGE-T; AGING-ASSOCIATED PHENOTYPES; CHECKPOINT PROTEIN BUB1; CELL-CYCLE PROGRESSION; KINETOCHORE LOCALIZATION; MITOTIC CHECKPOINT; SPINDLE CHECKPOINT; CHROMOSOME CONGRESSION; HUMAN-FIBROBLASTS AB Bub1 is a kinase believed to function primarily in the mitotic spindle checkpoint. Mutation or aberrant Bub1 expression is associated with chromosomal instability, aneuploidy, and human cancer. We now find that targeting Bub1 by RNAi or simian virus 40 (SV40) large T antigen in normal human diploid fibroblasts results in premature senescence. Interestingly, cells undergoing replicative senescence were also low in BUM expression, although ectopic BUM expression in presenescent cells was insufficient to extend lifespan. Premature senescence caused by lower Bub1 levels depends on p53. Senescence induction was blocked by dominant negative p53 expression or depletion of p21(CIP1), a p53 target. Importantly, cells with lower Bub1 levels and inactivated p53 became highly aneuploid. Taken together, our data highlight a role for p53 in monitoring Bub1 function, which may be part of a more general spindle checkpoint surveillance mechanism. Our data support the hypothesis that BUM compromise triggers p53-dependent senescence, which limits the production of aneuploid and potentially cancerous cells. C1 Univ Pittsburgh, Inst Canc, Mol Virol Program, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. UCL, Dept Neurodegenerat Dis, Inst Neurol, London WC1N 3BG, England. RP Gjoerup, OV (reprint author), Univ Pittsburgh, Inst Canc, Mol Virol Program, Pittsburgh, PA 15213 USA. EM ovg27@pitt.edu; thomas_roberts@dfci.harvard.edu FU NCI NIH HHS [CA34722, CA30002, P01 CA050661, P01-CA50661, R01 CA030002, R01 CA034722, R37 CA030002]; Wellcome Trust [072672] NR 49 TC 38 Z9 38 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 2007 VL 104 IS 20 BP 8334 EP 8339 DI 10.1073/pnas.0703164104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 169NW UT WOS:000246599900027 PM 17488820 ER PT J AU Hazen, RM Griffin, PL Carothers, JM Szostak, JW AF Hazen, Robert M. Griffin, Patrick L. Carothers, James M. Szostak, Jack W. TI Functional information and the emergence of biocomplexity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on In the Light of Evolution I CY DEC 01-02, 2006 CL Irvine, CA SP Natl Acad Sci, Arnold & Mabel Beckman Ctr DE origin of life; artificial life; evolution; aptamers; emergent systems ID SOCIAL AMEBAS; COMPLEXITY; GENOME; RNA; ORGANISMS; EVOLUTION; SELECTION; ADAPTATION; ROBUSTNESS; SEQUENCE AB Complex emergent systems of many interacting components, including complex biological systems, have the potential to perform quantifiable functions. Accordingly, we define "functional information," I(E-x), as a measure of system complexity. For a given system and function, x (e.g., a folded RNA sequence that binds to GTP), and degree of function, E-x (e.g., the RNA-GTP binding energy), I(E-x) = -log(2)[F(E-x)], where F(E-x) is the fraction of all possible configurations of the system that possess a degree of function >= E-x. Functional information, which we illustrate with letter sequences, artificial life, and biopolymers, thus represents the probability that an arbitrary configuration of a system will achieve a specific function to a specified degree. In each case we observe evidence for several distinct solutions with different maximum degrees of function, features that lead to steps in plots of information versus degree of function. C1 Carnegie Inst Sci, Geophys Lab, Washington, DC 20015 USA. Univ Calif Berkeley, Calif Inst Quantitat Biomed Res, Berkeley, CA 94720 USA. Univ Calif Berkeley, Berkeley Ctr Synth Biol, Berkeley, CA 94720 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Simches Res Ctr 7215, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Simches Res Ctr 7215, Boston, MA 02114 USA. RP Hazen, RM (reprint author), Carnegie Inst Sci, Geophys Lab, 5251 Broad Branch Rd NW, Washington, DC 20015 USA. EM rhazen@gl.ciw.edu NR 70 TC 40 Z9 42 U1 2 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 2007 VL 104 SU 1 BP 8574 EP 8581 DI 10.1073/pnas.0701744104 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 170WV UT WOS:000246697800003 PM 17494745 ER PT J AU Ilvesaro, JM Merrell, MA Swain, TM Davidson, J Zayzafoon, M Harris, KW Selander, KS AF Ilvesaro, Joanna M. Merrell, Melinda A. Swain, Telisha Millender Davidson, Jennifer Zayzafoon, Majd Harris, Kevin W. Selander, Katri S. TI Toll like receptor-9 agonists stimulate prostate cancer invasion in vitro SO PROSTATE LA English DT Article DE toll-like receptor 9; prostate cancer; invasion; matrix metalloproteinase-13 ID EPITHELIAL-CELLS; CPG-OLIGODEOXYNUCLEOTIDES; SUBCELLULAR-LOCALIZATION; HELICOBACTER-PYLORI; DENDRITIC CELLS; EXPRESSION; TLR9; ACTIVATION; RECOGNITION; ESTROGEN AB BACKGROUND. Toll-like receptor 9 (TLR9) recognizes microbial DNA. In addition to immune cells, TLR9 expression has been detected in various cancer cells. We showed recently that TLR9 agonistic CpG-oligonucleotides (CpG-ODNs) induce matrix metalloproteinase-13 (MMP-13)-mediated invasion in TLR9-expressing (TLR9(+)) breast cancer cells. We investigated here TLR9 expression and function in human prostate cancer (CaP) cells. METHODS. TLR9 expression was detected with Western blotting and immunohistochemistry. Invasion was studied with Matrigel-assays. MMP-13 was assayed with ELISA. RESULTS. Human CaP cell lines and clinical samples exhibit various levels of TLR9 expression. Treatment of TLR9+, but not TLR9(-) CaP cells with CpG-ODNs or bacterial DNA increased their invasion, which was inhibited with chloroquine. CpG-ODN-treatment also increased MMP-13 activity and neutralizing anti-MMP-13 antibody prevented CpG-ODNinduced invasion in TLR9+ Cap cells. Estradiol up-regulated TLR9 expression in LnCaP cells. CONCLUSIONS. TLR9-mediated invasion may represent a novel mechanism through which infections promote prostate cancer. C1 UAB, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. UAB, Dept Pathol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Selander, KS (reprint author), UAB, Dept Med, Div Hematol Oncol, WTI T558,1824 6th Ave S, Birmingham, AL 35294 USA. EM Katri.Selander@ccc.uab.edu NR 47 TC 100 Z9 109 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY 15 PY 2007 VL 67 IS 7 BP 774 EP 781 DI 10.1002/pros.20562 PG 8 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 161NM UT WOS:000246022200010 PM 17373717 ER PT J AU Dhingra, R Sullivan, LM Fox, CS Wang, TJ D'Agostino, RB Gaziano, JM Vasan, RS AF Dhingra, Ravi Sullivan, Lisa M. Fox, Caroline S. Wang, Thomas J. D'Agostino, Ralph B. Gaziano, J. Michael Vasan, Ramachandran S. TI Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; PARATHYROID-HORMONE; MORTALITY RISK; HEMODIALYSIS-PATIENTS; BLOOD-PRESSURE; RENAL-DISEASE; YOUNG-ADULTS; KLOTHO GENE; PHOSPHATE; CALCIFICATION AB Background: Higher levels of serum phosphorus and the calcium-phosphorus product are associated with increased mortality from cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) or prior CVD. However, it is unknown if serum phosphorus levels influence vascular risk in individuals without CKD or CVD. Methods: We prospectively evaluated 3368 Framingham Offspring study participants (mean age, 44 years; 51% were women) free of CVD and CKD. We used multivariable Cox models to relate serum phosphorus and calcium levels to CVD incidence. Results: On follow-up (mean duration, 16.1 years), there were 524 incident CVD events (159 in women). In multivariable analyses and adjusting for established risk factors and additionally for glomerular filtration rate and for hemoglobin, serum albumin, proteinuria, and C-reactive protein levels, a higher level of serum phosphorus was associated with an increased CVD risk in a continuous fashion (adjusted hazard ratio per increment of milligrams per deciliter, 1.31; 95% confidence interval, 1.05-1.63; P = .02; P value for trend across quartiles =. 004). Individuals in the highest serum phosphorus quartile experienced a multivariable-adjusted 1.55-fold CVD risk (95% confidence interval, 1.16%-2.07%; P = .004) compared with those in the lowest quartile. These findings remained robust in time-dependent models that up-dated CVD risk factors every 4 years and in analyses restricted to individuals without proteinuria and an estimated glomerular filtration rate greater than 90 mL/min per 1.73 m(2). Serum calcium was not related to CVD risk. Conclusion: Higher serum phosphorus levels are associated with an increased CVD risk in individuals free of CKD and CVD in the community. These observations emphasize the need for additional research to elucidate the potential link between phosphorus homeostasis and vascular risk. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Brigham & Womens Hosp, Masachusetts Vet Epidemiol Res & Informat Ctr, Vet Adm Boston Healthcare Syst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Alice Peck Day Mem Hosp, Dept Med, Lebanon, NH USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Dept Prevent Med & Epidemiol, Sch Med, Boston, MA 02215 USA. NHLBI, Bethesda, MD USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K23HL74077, 1R01HL67288, 2K24HL04334, N01-HC-25195] NR 46 TC 397 Z9 413 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 14 PY 2007 VL 167 IS 9 BP 879 EP 885 DI 10.1001/archinte.167.9.879 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 167LX UT WOS:000246454300004 PM 17502528 ER PT J AU Desjardins, AE Vakoc, BJ Oh, WY Motaghiannezam, SMR Tearney, GJ Bouma, BE AF Desjardins, A. E. Vakoc, B. J. Oh, W. Y. Motaghiannezam, S. M. R. Tearney, G. J. Bouma, B. E. TI Angle-resolved Optical Coherence Tomography with sequential angular selectivity for speckle reduction SO OPTICS EXPRESS LA English DT Article ID SWEPT SEMICONDUCTOR-LASER; MICROSCOPY; STATISTICS; FILTER AB We present a novel method for rapidly acquiring optical coherence tomography ( OCT) images at multiple backscattering angles. By angularly compounding these images, high levels of speckle reduction were achieved. Signal-to-noise ratio (SNR) improvements of 3.4 dB were obtained from a homogeneous tissue phantom, which was in good agreement with the predictions of a statistical model of speckle that incorporated the optical parameters of the imaging system. In addition, the fast acquisition rate of the system (10 kHz A-line repetition rate) allowed angular compounding to be performed in vivo without significant motion artifacts. Speckle-reduced OCT images of human dermis show greatly improved delineation of tissue microstructure. (C) 2006 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Desjardins, AE (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 708, Boston, MA 02114 USA. EM adesjard@fas.harvard.edu RI Oh, Wang-Yuhl/C-2055-2011 FU NCI NIH HHS [R01 CA103769, R01 CA103769-04]; NHLBI NIH HHS [R01 HL076398, R01 HL076398-05] NR 14 TC 56 Z9 58 U1 2 U2 18 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 MAY 14 PY 2007 VL 15 IS 10 BP 6200 EP 6209 DI 10.1364/OE.15.006200 PG 10 WC Optics SC Optics GA 167TH UT WOS:000246474300034 PM 19546925 ER PT J AU Chan, AT AF Chan, Andrew T. TI Can aspirin prevent colorectal cancer? SO LANCET LA English DT Editorial Material ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-DOSE ASPIRIN; RANDOMIZED-TRIAL; RISK; ADENOMAS; HEALTH C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02116 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02116 USA. EM achan@partners.org NR 14 TC 5 Z9 5 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 12 PY 2007 VL 369 IS 9573 BP 1577 EP 1578 DI 10.1016/S0140-6736(07)60720-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 167YO UT WOS:000246488800004 PM 17499581 ER PT J AU Walensky, RP Weinstein, MC Yazdanpanah, Y Losina, E Mercincavage, LM Toure, S Divi, N Anglaret, X Goldie, SJ Freedberg, KA AF Walensky, Rochelle P. Weinstein, Milton C. Yazdanpanah, Yazdan Losina, Elena Mercincavage, Lauren M. Toure, Siaka Divi, Nomita Anglaret, Xavier Goldie, Sue J. Freedberg, Kenneth A. CA CEPAC International Investigators TI HIV drug resistance surveillance for prioritizing treatment in resource-limited settings SO AIDS LA English DT Article DE HIV/AIDS; sentinel resistance; Africa ID COST-EFFECTIVENESS ANALYSIS; ANTIRETROVIRAL THERAPY; HIV-1-INFECTED ADULTS; COTE-DIVOIRE; INFECTED PATIENTS; CLINICAL IMPACT; TRIAL; COMBINATION; NELFINAVIR; NEVIRAPINE AB Background: Sentinel testing programs for HIV drug resistance in resource-limited settings can inform policy on antiretroviral therapy (ART) and drug sequencing. Objective: To examine the value of resistance surveillance in influencing recommendations toward effective and cost-effective sequencing of ART regimens. Methods: A state-transition model of HIV infection was adapted to simulate clinical care in Cote d'Ivoire and evaluate the incremental cost-effectiveness of (1) no ART; (2) ART beginning with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen followed by a boosted protease inhibitor (PI)-based regimen; and (3) ART beginning with a boosted PI-based regimen followed by an NNRTI-based regimen. Results: At a 5% prevalence of NNRTI resistance, a strategy that started with a PI-based regimen had a smaller health benefit and higher cost-effectiveness ratio than a strategy that started with an NNRTI-based regimen (cost-effectiveness ratio $910/year of life saved). Results consistently favored initiation with an NNRTI-based regimen, regardless of the population prevalence of NNRTI resistance (up to 76%) and the efficacy of an NNRTI-based regimen in the setting of resistance. The most influential parameters on the cost-effectiveness of sequencing strategies were boosted PI-based regimen costs and the efficacy of this regimen when used as second-line therapy. Conclusions: Drug costs and treatment efficacies, but not NNRTI resistance levels, were most influential in determining optimal HIV drug sequencing in Cote d'Ivoire. Results of surveillance for NNRTI resistance should not be used as a major guide to treatment policy in resource-limited settings. (C) 2007 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Ctr Hosp Tourcoing, Serv Univ Maladies Infect & Voyageur, Lille, France. Fac Med Lille, EA 2694, F-59045 Lille, France. CNRS, URA 362, Lab Rech Econ & Sociales, Lille, France. INSERM, U593, Bordeaux, France. Programme PAC CI, Abidjan, Cote Ivoire. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Div Gen Med, 9th Floor,50 Staniford St, Boston, MA 02114 USA. EM rwalensky@partners.org RI Anglaret, Xavier/F-7333-2013 FU NIAID NIH HHS [K23 AI001794, K23 AI001794-05, K23 AI01794, K24 AI062476, K24 AI062476-01, K25 AI050436, K25 AI050436-05, K25 AI50436, P30 AI042851, P30 AI042851-05, P30 AI42851, R01 AI058736, R01 AI058736-01A1] NR 40 TC 21 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 11 PY 2007 VL 21 IS 8 BP 973 EP 982 DI 10.1097/QAD.0b013e328011ec53 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 171RW UT WOS:000246754100010 PM 17457091 ER PT J AU Faraone, SV Adamson, JJ Wilens, TE Monuteaux, MC Biederman, J AF Faraone, Stephen V. Adamson, Joel J. Wilens, Timothy E. Monuteaux, Michael C. Biederman, Joseph TI Deriving phenotypes for molecular genetic studies of substance use disorders: A family study approach SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE factor analysis; substance use disorders; genetic studies ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC COMORBIDITY; BEHAVIORAL-INHIBITION; ANXIETY DISORDERS; BIPOLAR DISORDER; FOLLOW-UP; ASSOCIATION; ALCOHOLISM; CHILDREN; COCAINE AB Although, family, twin, and adoption studies indicate that genes play a significant etiologic role in the development of substance use disorders (SUDs), the specific genes involved have been difficult to detect due, in part, to uncertainties about how best to define SUDs, the possibility of genetic heterogeneity and the variable phenotypic expression of SUD genotypes. The goal of the present work was to determine if phenotypes external to the diagnosis of SUD such as psychopathology and cognitive functioning would show evidence of utility as phenotypes for genetic studies of SUD. We did this by applying factor analysis to multiple measures collected from our family-study program and then determining if these factors were heritable and were co-familial with SUDs. We used data from families recruited into six contemporaneous studies of four psychiatric conditions in children and adults. We found evidence for two SUD related phenotypes. One was an index of Psychopathology and Psychosocial Impairment; the other was an index of school failure and cognitive dysfunction. Both factors showed evidence of heritability, longitudinal stability and familial association with Parental SUD but these findings were stronger for the index of school failure and cognitive dysfunction. Results provide some support for the idea that candidate SUD phenotypes such as psychopathology and cognitive functioning, which are external to the diagnostic criteria for SUDs, may be useful for genetic studies of SUD. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY 13210 USA. Harvard Univ, Sch Med, Dept Psychiat,Yawkey Ctr Outpatient Care, Massachusetts Gen Hosp,Pediat Psychopharmacol Uni, Boston, MA 02114 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Adamson, Joel/0000-0002-1399-5786; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01MH57934] NR 51 TC 5 Z9 5 U1 0 U2 2 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 MAY 11 PY 2007 VL 88 IS 2-3 BP 244 EP 250 DI 10.1016/j.drugalcdep.2006.11.002 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 162EG UT WOS:000246069000016 PM 17141426 ER PT J AU Maeda, T Merghoub, T Hobbs, RM Dong, L Maeda, M Zakrzewski, J van den Brink, MRM Zelent, A Shigematsu, H Akashi, K Teruya-Feldstein, J Cattoretti, G Pandolfi, PP AF Maeda, Takahiro Merghoub, Taha Hobbs, Robin M. Dong, Lin Maeda, Manami Zakrzewski, Johannes van den Brink, Marcel R. M. Zelent, Arthur Shigematsu, Hirokazu Akashi, Koichi Teruya-Feldstein, Julie Cattoretti, Giorgio Pandolfi, Pier Paolo TI Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF SO SCIENCE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; ZINC-FINGER PROTEIN; MOUSE BONE-MARROW; DIFFERENTIATION; NOTCH1; MICE; MAINTENANCE; PROGENITORS; APOPTOSIS AB Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors, which subsequently differentiate into B and T lymphocytes. Here we show that the proto-oncogene LRF plays an essential role in the B versus T lymphoid cell-fate decision. We demonstrate that LRF is key for instructing early lymphoid progenitors in mice to develop into B lineage cells by repressing T cell-instructive signals produced by the cell-fate signal protein, Notch. We propose a new model for lymphoid lineage commitment, in which LRF acts as a master regulator of the cell's determination of B versus T lineage. C1 Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Inst Canc Res, Leukemia Res Fund Ctr, Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. RP Pandolfi, PP (reprint author), Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, 1275 York Ave, New York, NY 10021 USA. EM p-pandolfi@ski.mskcc.org RI Zelent, Arthur/B-3532-2009; OI Hobbs, Robin/0000-0002-3853-2614 FU NCI NIH HHS [R01 CA102142, CA-102142, R01 CA102142-06A1] NR 27 TC 131 Z9 136 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 11 PY 2007 VL 316 IS 5826 BP 860 EP 866 DI 10.1126/science.1140881 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 166HM UT WOS:000246369800030 PM 17495164 ER PT J AU Schweiger, M Nissila, I Boas, DA Arridge, SR AF Schweiger, Martin Nissila, Ilkka Boas, David A. Arridge, Simon R. TI Image reconstruction in optical tomography in the presence of coupling errors SO APPLIED OPTICS LA English DT Article ID CALIBRATION METHOD; RADIATIVE-TRANSFER; SCATTERING MEDIA; TISSUE; SPECTROSCOPY; TRANSPORT; BOUNDARY; EQUATION; PHANTOMS; LIGHT AB Image reconstruction in optical tomography is a nonlinear and generally ill-posed inverse problem. Noise in the measured surface data can give rise to substantial artifacts in the recovered volume images of optical coefficients. Apart from random shot noise caused by the limited number of photons detected at the measurement site, another class of systematic noise is associated with losses specific to individual source and detector locations. A common cause for such losses in data acquisition systems based on fiber-optic light delivery is the imperfect coupling between the fiber tips and the skin of the patient because of air gaps or surface moisture. Thus the term coupling errors was coined for this type of data noise. However, source and detector specific errors can also occur in noncontact measurement systems not using fiber-optic delivery, for example, owing to local skin pigmentation, hair and hair follicles, or instrumentation calibration errors. Often it is not possible to quantify coupling effects in a way that allows us to remove them from the data or incorporate them into the light transport model. We present an alternative method of eliminating coupling errors by regarding the complex-valued coupling factors for each source and detector as unknowns in the reconstruction process and recovering them simultaneously with the images of absorption and scattering. Our method takes into account the possibility that coupling effects have an influence on both the amplitude and the phase shift of the measurements. Reconstructions from simulated and experimental phantom data are presented, which show that including the coupling coefficients in the reconstruction greatly improves the recovery of absorption and scattering images. (c) 2007 Optical Society of America. C1 UCL, Ctr Med Image Comp, London WC1E 6BT, England. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Aalto Univ, Biomed Engn Lab, Helsinki 02015, Finland. RP Schweiger, M (reprint author), UCL, Ctr Med Image Comp, Mortimer St, London WC1E 6BT, England. EM M.Schweiger@cs.ucl.ac.uk RI Nissila, Ilkka/G-6879-2012 OI Nissila, Ilkka/0000-0001-6534-8436 NR 27 TC 23 Z9 23 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD MAY 10 PY 2007 VL 46 IS 14 BP 2743 EP 2756 DI 10.1364/AO.46.002743 PG 14 WC Optics SC Optics GA 164MK UT WOS:000246237900022 PM 17446924 ER PT J AU Mikkelsen, TS Wakefield, MJ Aken, B Amemiya, CT Chang, JL Duke, S Garber, M Gentles, AJ Goodstadt, L Heger, A Jurka, J Kamal, M Mauceli, E Searle, SMJ Sharpe, T Baker, ML Batzer, MA Benos, PV Belov, K Clamp, M Cook, A Cuff, J Das, R Davidow, L Deakin, JE Fazzari, MJ Glass, JL Grabherr, M Greally, JM Gu, WJ Hore, TA Huttley, GA Kleber, M Jirtle, RL Koina, E Lee, JT Mahony, S Marra, MA Miller, RD Nicholls, RD Oda, M Papenfuss, AT Parra, ZE Pollock, DD Ray, DA Schein, JE Speed, TP Thompson, K VandeBerg, JL Wade, CM Walker, JA Waters, PD Webber, C Weidman, JR Xie, XH Zody, MC Graves, JAM Ponting, CP Breen, M Samollow, PB Lander, ES Lindblad-Toh, K AF Mikkelsen, Tarjei S. Wakefield, Matthew J. Aken, Bronwen Amemiya, Chris T. Chang, Jean L. Duke, Shannon Garber, Manuel Gentles, Andrew J. Goodstadt, Leo Heger, Andreas Jurka, Jerzy Kamal, Michael Mauceli, Evan Searle, Stephen M. J. Sharpe, Ted Baker, Michelle L. Batzer, Mark A. Benos, Panayiotis V. Belov, Katherine Clamp, Michele Cook, April Cuff, James Das, Radhika Davidow, Lance Deakin, Janine E. Fazzari, Melissa J. Glass, Jacob L. Grabherr, Manfred Greally, John M. Gu, Wanjun Hore, Timothy A. Huttley, Gavin A. Kleber, Michael Jirtle, Randy L. Koina, Edda Lee, Jeannie T. Mahony, Shaun Marra, Marco A. Miller, Robert D. Nicholls, Robert D. Oda, Mayumi Papenfuss, Anthony T. Parra, Zuly E. Pollock, David D. Ray, David A. Schein, Jacqueline E. Speed, Terence P. Thompson, Katherine VandeBerg, John L. Wade, Claire M. Walker, Jerilyn A. Waters, Paul D. Webber, Caleb Weidman, Jennifer R. Xie, Xiaohui Zody, Michael C. Graves, Jennifer A. Marshall Ponting, Chris P. Breen, Matthew Samollow, Paul B. Lander, Eric S. Lindblad-Toh, Kerstin CA Broad Inst Genome Sequencing Platf Broad Inst Whole Genome Assembly TI Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences SO NATURE LA English DT Review ID X-CHROMOSOME INACTIVATION; SHORT-TAILED OPOSSUM; RECOMBINATION RATES; TRANSPOSABLE ELEMENTS; VERTEBRATE EVOLUTION; REGULATORY NETWORKS; MAMMALIAN EVOLUTION; MOBILE ELEMENTS; GENE DESERTS; MOUSE AB We report a high-quality draft of the genome sequence of the grey, short-tailed opossum ( Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation. C1 MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Cambridge, MA 02142 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Walter & Eliza Hall Inst Med Res, Bioinformat Div, Parkville, Vic 3050, Australia. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Benaroya Res Inst Virginia Mason, Mol Genet Program, Seattle, WA 98101 USA. N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Genet Informat Res Inst, Mountain View, CA 94043 USA. Univ Oxford, MRC Funct Genet Unit, Dept Physiol Anat & Genet, Oxford OX1 3QX, England. Univ New Mexico, Ctr Evolutionary & Theoret Immunol, Dept Biol, Albuquerque, NM 87131 USA. Louisiana State Univ, Ctr Biomodular Multiscale Syst, Dept Biol Sci, Biol Computat & Visualizat Ctr, Baton Rouge, LA 70803 USA. Univ Pittsburgh, Dept Computat Biol, Pittsburgh, PA 15260 USA. Univ Sydney, Fac Vet Sci, Sydney, NSW 2006, Australia. Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Australian Natl Univ, Res Sch Biol Sci, ARC Ctr Kangaroo Genom, Canberra, ACT 2601, Australia. Yeshiva Univ Albert Einstein Coll Med, Dept Med Hematol & Mol Genet, Bronx, NY 10461 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Aurora, CO 80045 USA. Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 0200, Australia. British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z4S6, Canada. Childrens Hosp Pittsburgh, Res Ctr, Dept Pediat, Pittsburgh, PA 15213 USA. W Virginia Univ, Dept Biol, Morgantown, WV 26505 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. SW Fdn Biomed Res, SW Natl Primate Res Ctr, San Antonio, TX 78245 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. N Carolina State Univ, Ctr Comparat Med & Translat Res, Raleigh, NC 27606 USA. Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Lindblad-Toh, K (reprint author), MIT, Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM tarjei@broad.mit.edu; lander@broad.mit.edu; kersli@broad.mit.edu RI Schein, Jacquie/G-3674-2015; Mikkelsen, Tarjei/A-1306-2007; Wakefield, Matthew/A-7795-2008; Graves, Jennifer/A-1387-2008; Deakin, Janine/A-1941-2008; Speed, Terence /B-8085-2009; Waters, Paul/D-1044-2009; Baker, Michelle/C-9694-2013; Gu, Wanjun/B-3998-2010; Mahony, Shaun/C-5699-2014; Tang, Macy/B-9798-2014; Waters, Paul/B-7871-2015; Huttley, Gavin/G-5169-2015; Marra, Marco/B-5987-2008; Pollock, David/M-4740-2016; Papenfuss, Anthony/C-6297-2008; OI Mikkelsen, Tarjei/0000-0002-8133-3135; Wakefield, Matthew/0000-0001-6624-4698; Deakin, Janine/0000-0002-1259-3531; Speed, Terence /0000-0002-5403-7998; Mahony, Shaun/0000-0002-2641-1807; Huttley, Gavin/0000-0001-7224-2074; Heger, Andreas/0000-0001-7720-0447; Pollock, David/0000-0002-7627-4214; Papenfuss, Anthony/0000-0002-1102-8506; Wade, Claire/0000-0003-3413-4771; Aken, Bronwen/0000-0002-3032-4095; Benos, Panayiotis/0000-0003-3172-3132; Hore, Timothy/0000-0002-6735-225X; Ponting, Chris/0000-0003-0202-7816 FU Medical Research Council [MC_U137761446]; Wellcome Trust [062023] NR 109 TC 426 Z9 437 U1 6 U2 51 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 10 PY 2007 VL 447 IS 7141 BP 167 EP U1 DI 10.1038/nature05805 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 165WT UT WOS:000246338700035 PM 17495919 ER PT J AU Ting, DT Butterton, JR Romero, JM Collier, DS Zembowicz, A Bazari, H AF Ting, David T. Butterton, Joan R. Romero, Javier M. Collier, Deborah S. Zembowicz, Artur Bazari, Hasan TI A 59-year-old man with fever and pain and swelling of both eyes and the right ear - Relapsing polychondritis, with involvement of both eyes, the right ear, the nose, and the aortic root, with vasculitis of the internal carotid arteries. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BACTERIAL SINUSITIS; RHEUMATIC-DISEASES; EXTERNAL OTITIS; II COLLAGEN; ANTIBODIES; VESSEL C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Ting, DT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 10 PY 2007 VL 356 IS 19 BP 1980 EP 1988 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 165KX UT WOS:000246305500011 ER PT J AU Mercaldo, ND Lau, KF Zhou, XH AF Mercaldo, Nathaniel D. Lau, Kit F. Zhou, Xiao H. TI Confidence intervals for predictive values with an emphasis to case-control studies SO STATISTICS IN MEDICINE LA English DT Article DE predictive values; confidence intervals; diagnostic tests; Alzheimer's disease; breast cancer ID ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; BREAST-CANCER; ASSOCIATION; PREVALENCE; ALLELE AB The accuracy of a binary-scale diagnostic test can be represented by sensitivity (Se), specificity (Sp) and positive and negative predictive values (PPV and NPV). Although Se and Sp measure the intrinsic accuracy of a diagnostic test that does not depend on the prevalence rate, they do not provide information on the diagnostic accuracy of a particular patient. To obtain this information we need to use PPV and NPV. Since PPV and NPV are functions of both the accuracy of the test and the prevalence of the disease, constructing their confidence intervals for a particular patient is not straightforward. In this paper, a novel method for the estimation of PPV and NPV, as well as their confidence intervals, is developed. For both predictive values, standard, adjusted and their logit transformed-based confidence intervals are compared using coverage probabilities and interval lengths in a simulation study. These methods are then applied to two case-control studies: a diagnostic test assessing the ability of the e4 allele of the apolipoprotein E gene (ApoE.e4) on distinguishing patients with late-onset Alzheimer's disease (AD) and a prognostic test assessing the predictive ability of a 70-gene signature on breast cancer metastasis. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Univ Washington, Dept Biostat, Seattle, WA 98027 USA. Celera Diagnost, Alameda, CA USA. VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98027 USA. EM azhou@u.washington.edu NR 16 TC 30 Z9 30 U1 2 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 10 PY 2007 VL 26 IS 10 BP 2170 EP 2183 DI 10.1002/sim.2677 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 160TM UT WOS:000245965200003 PM 16927452 ER PT J AU Giordano, TP Henderson, L Landgren, O Chiao, EY Kramer, JR El-Serag, H Engels, EA AF Giordano, Thomas P. Henderson, Louise Landgren, Ola Chiao, Elizabeth Y. Kramer, Jennifer R. El-Serag, Hashem Engels, Eric A. TI Risk of non-Hodgkin lymphoma and lymphoproliferative precursor diseases in US veterans with hepatitis C virus SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ADMINISTRATION MEDICAL SYSTEM; THYROID-CANCER; UNITED-STATES; WALDENSTROM MACROGLOBULINEMIA; MONOCLONAL GAMMOPATHY; INFECTION; PREVALENCE; CRYOGLOBULINEMIA; ASCERTAINMENT; REGRESSION AB Context Hepatitis C virus (HCV) infection causes liver cancer and cirrhosis and may also increase the risk of other tumors, particularly hematopoietic malignancies and thyroid cancer. Previous studies have been too small to adequately assess these risks. Objective To test the hypothesis that HCV infection is associated with increased risk for hematological malignancies, related lymphoproliferative disorders, and thyroid cancer. Design, Setting, and Patients A retrospective cohort study of users of US Veterans Affairs health care facilities from 1997-2004, which included 146 394 patients infected with HCV who had at least 2 visits with a diagnostic code for HCV infection, and 572 293 patients uninfected with HCV. To assemble the HCV-uninfected cohort, we randomly selected up to 4 patients per patient infected with HCV from all veterans who matched on age, sex, and baseline visit date and type (inpatient or outpatient). Individuals with human immunodeficiency virus were excluded. Main Outcome Measures Risks of hematopoietic malignancies, related lymphoproliferative precursor diseases, and thyroid cancer, adjusting for selection factors, race, era of military service, and use of medical services. Results The mean (SD) age of the patients was 52 (8) years, and 97% were men. Risks for non-Hodgkin lymphoma (n = 1359), Waldenstrom macroglobulinemia (n = 165), and cryoglobulinemia (n = 551) were increased with HCV infection (adjusted hazard ratio [ HR], 1.28; 95% confidence interval [ CI], 1.12-1.45; adjusted HR, 2.76; 95% CI, 2.01-3.79; and adjusted HR, 3.98; 95% CI, 3.36-4.72; respectively). We found no significantly increased risk for other hematological malignancies. Although thyroiditis risk was slightly increased, risk for thyroid cancer (n = 320) was not (adjusted HR, 0.72; 95% CI, 0.52-0.99). Adjusted P values for non-Hodgkin lymphoma, Waldenstrom macroglobulinemia, cryoglobulinemia, and thyroiditis were all < .0038, the Bonferroni threshold for statistical significance considering multiple comparisons. Conclusions Hepatitis C virus infection confers a 20% to 30% increased risk of non-Hodgkin lymphoma overall, and a 3-fold higher risk of Waldenstrom macroglobulinemia, a low-grade lymphoma. Risks were also increased for cryoglobulinemia. These results support an etiological role for HCV in causing lymphoproliferation and causing non-Hodgkin lymphoma. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NCI, NIH, Rockville, MD USA. RP Giordano, TP (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, VA152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM tpg@bcm.tmc.edu FU Intramural NIH HHS; NCI NIH HHS [K23CA124318]; NIMH NIH HHS [K23MH67505] NR 27 TC 167 Z9 174 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 9 PY 2007 VL 297 IS 18 BP 2010 EP 2017 DI 10.1001/jama.297.18.2010 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 165JM UT WOS:000246301800023 PM 17488966 ER PT J AU Finn, AV Joner, M Nakazawa, G Kolodgie, F Newell, J John, MC Gold, HK Virmani, R AF Finn, Aloke V. Joner, Michael Nakazawa, Gaku Kolodgie, Frank Newell, John John, Mike C. Gold, Herman K. Virmani, Renu TI Pathological correlates of late drug-eluting stent thrombosis - Strut coverage as a marker of endothelialization SO CIRCULATION LA English DT Article DE complications; stents; thrombus; pathology; endothelium ID CORONARY-ARTERY; PACLITAXEL; PREDICTORS; HUMANS; IMPLANTATION AB Background - Late stent thrombosis (LST) after Cypher and Taxus drug-eluting stent placement has emerged as a major concern. Although the clinical predictors of LST have been reported, specific morphological and histological correlates of LST remain unknown. Methods and Results - From a registry totaling 81 human autopsies of drug-eluting stents, 46 (62 lesions) had a drug-eluting stent implanted > 30 days. We identified 28 lesions with thrombus and compared those with 34 of similar duration without thrombosis using computer-guided morphometric and histological analyses. LST was defined as an acute thrombus within a coronary artery stent in place > 30 days. Multiple logistic generalized estimating equations modeling demonstrated that endothelialization was the best predictor of thrombosis. The morphometric parameter that best correlated with endothelialization was the ratio of uncovered to total stent struts per section. A univariable logistic generalized estimating equations model of occurrence of thrombus in a stent section versus ratio of uncovered to total stent struts per section demonstrated a marked increase in risk for LST as the number of uncovered struts increased. The odds ratio for thrombus in a stent with a ratio of uncovered to total stent struts per section > 30% is 9.0 (95% CI, 3.5 to 22). Conclusions - The most powerful histological predictor of stent thrombosis was endothelial coverage. The best morphometric predictor of LST was the ratio of uncovered to total stent struts. Heterogeneity of healing is a common finding in drug-eluting stents with evidence of LST and demonstrates the importance of incomplete healing of the stented segment in the pathophysiology of LST. C1 CVPath, Int Registry Pathol, Gaithersburg, MD 20878 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Partners Healthcare Syst, Boston, MA USA. RP Virmani, R (reprint author), CVPath, Int Registry Pathol, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 18 TC 729 Z9 770 U1 7 U2 32 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 8 PY 2007 VL 115 IS 18 BP 2435 EP 2441 DI 10.1161/CIRCULATIONAHA.107.693739 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 165BE UT WOS:000246278000011 PM 17438147 ER PT J AU Rohas, LM St-Pierre, J Uldry, M Jager, S Handschin, C Spiegelman, BM AF Rohas, Lindsay M. St-Pierre, Julie Uldry, Marc Jager, Sibylle Handschin, Christoph Spiegelman, Bruce M. TI A fundamental system of cellular energy homeostasis regulated by PGC-1 alpha SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mitochondria; uncoupling ID ACTIVATED PROTEIN-KINASE; CONTROLLING MITOCHONDRIAL BIOGENESIS; CREB COACTIVATOR TORC2; ADAPTIVE THERMOGENESIS; METABOLIC STRESS; MAMMALIAN-CELLS; SKELETAL-MUSCLE; BROWN FAT; CALCIUM; TRANSCRIPTION AB Maintenance of ATP levels is a critical feature of all cells. Mitochondria are responsible for most ATP synthesis in eukaryotes. We show here that mammalian cells respond to a partial chemical uncoupling of mitochondrial oxidative phosphorylation with a decrease in ATP levels, which recovers over several hours to control levels. This recovery occurs through an increased expression of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1 alpha (PGC-1 alpha) and mitochondrial genes. Cells and animals lacking PGC-1 alpha lose this compensatory mechanism and cannot defend their ATP levels or increase mitochondrial gene expression in response to reduced oxidative phosphorylation. The induction of PGC-1 alpha and its mitochondrial target genes is triggered by a burst of intracellular calcium, which causes an increase in cAMP-response-element-binding protein and transducer of regulated cAMP-response-element-binding proteins actions on the PGC-1 alpha promoter. These data illustrate a fundamental transcriptional cycle that provides homeostatic control of cellular ATP. In light of this compensatory system that limits the toxicity of mild uncoupling, the use of chemical uncoupling of mitochondria as a means of treating obesity should be re-evaluated. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NIDDK NIH HHS [P30 DK040561, DK54477, DK61562, P30 DK040561-12, R01 DK054477, R01 DK060837, R01 DK061562, R01DK060837, R56 DK054477]; NIGMS NIH HHS [2-T32-GM07226-27, T32 GM007226] NR 54 TC 117 Z9 121 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 8 PY 2007 VL 104 IS 19 BP 7933 EP 7938 DI 10.1073/pnas.0702683104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 167OR UT WOS:000246461500038 PM 17470778 ER PT J AU Boucrot, E Kirchhausen, T AF Boucrot, Emmanuel Kirchhausen, Tomas TI Endosomal recycling controls plasma membrane area during mitosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE clathrin; endocytosis; exocytosis; cell division; dynasore ID CELL-SURFACE; MITOTIC SPINDLE; GOLGI-APPARATUS; CLEAVAGE FURROW; COATED PITS; BREFELDIN-A; HELA-CELLS; CYTOKINESIS; ENDOCYTOSIS; DYNAMIN AB The shape and total surface of a cell and its daughters change during mitosis. Many cells round up during prophase and metaphase and reacquire their extended and flattened shape during cytokinesis. How does the total area of plasma membrane change to accommodate these morphological changes and by what mechanism is control of total membrane area achieved? Using single-cell imaging methods, we have found that the amount of plasma membrane in attached cells in culture decreases at the beginning of mitosis and recovers rapidly by the end. Clathrin-based endocytosis is normal throughout all phases of cell division, whereas recycling of internalized membranes back to the cell surface slows considerably during the rounding up period and resumes at the time at which recovery of cell membrane begins. Interference with either one of these processes by genetic or chemical means impairs cell division. The total cell-membrane area recovers even in the absence of a functional Golgi apparatus, which would be needed for export of newly synthesized membrane lipids and proteins. We propose a mechanism by which modulation of endosomal recycling controls cell area and surface expression of membrane-bound proteins during cell division. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu FU NIGMS NIH HHS [GM075252, P01 GM062566, R01 GM075252, GM62566] NR 53 TC 169 Z9 169 U1 1 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 8 PY 2007 VL 104 IS 19 BP 7939 EP 7944 DI 10.1073/pnas.0702511104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 167OR UT WOS:000246461500039 PM 17483462 ER PT J AU Chang, JD Sukhova, GK Libby, P Schvartz, E Lichtenstein, AH Field, SJ Kennedy, C Madhavarapu, S Luo, J Wu, DQ Cantley, LC AF Chang, James D. Sukhova, Galina K. Libby, Peter Schvartz, Eugenia Lichtenstein, Alice H. Field, Seth J. Kennedy, Caitlin Madhavarapu, Swetha Luo, Ji Wu, Dianqing Cantley, Lewis C. TI Deletion of the phosphoinositide 3-kinase p110 gamma gene attenuates murine atherosclerosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Akt; inflammation; macrophage; lipoproteins; G protein-coupled receptors ID C-REACTIVE PROTEIN; LOW-DENSITY-LIPOPROTEIN; E-DEFICIENT MICE; APOLIPOPROTEIN-E; PHOSPHATIDYLINOSITOL 3-KINASE; MACROPHAGE PROLIFERATION; EMBRYONIC LETHALITY; CATALYTIC SUBUNIT; CELL-ACTIVATION; IN-VITRO AB inflammatory cell activation by chemokines requires intracellular signaling through phosphoinositide 3-kinase (PI3-kinase) and the PI3-kinase-dependent protein serine/threonine kinase Akt. Atherosclerosis is a chronic inflammatory process driven by oxidatively modified (atherogenic) lipoproteins, chemokines, and other agonists that activate PI3-kinase. Here we show that macrophage PI3-kinase/Akt is activated by oxidized low-density lipoprotein, inflammatory chemokines, and angiotensin II. This activation is markedly reduced or absent in macrophages lacking p110 gamma, the catalytic subunit of class lb PI3-kinase. We further demonstrate activation of macrophage/foam cell PI3-kinase/Akt in atherosclerotic plaques from apolipoprotein E (apoE)-null mice, which manifest an aggressive form of atherosclerosis, whereas activation of PI3-kinase/Akt was undetectable in lesions from apoE-null mice lacking p110 gamma despite the presence of class Ia PI3-kinase. Moreover, plaques were significantly smaller in apoE(-/-)p110 gamma(-/-) mice than in apoE(-/-)p110 gamma(+/+) or apoE(-/-)p110 gamma(+/-)mice at all ages studied. In marked contrast to the embryonic lethality seen in mice lacking class Ia PI3-kinase, germ-line deletion of p110 gamma results in mice that exhibit normal viability, longevity, and fertility, with relatively well tolerated defects in innate immune and inflammatory responses that may play a role in diseases such as atherosclerosis and multiple sclerosis. Our results not only shed mechanistic light on inflammatory signaling during atherogenesis, but further identify p110 gamma as a possible target for pharmacological intervention in the primary and secondary prevention of human atherosclerotic cardiovascular disease. C1 Beth Israel Deaconess Med Ctr, Signal Transduct Div, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Donald W Reynolds Cardiovasc Clin Res Ctr, Cardiovasc Div, Boston, MA 02115 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Cardiovasc Nutr Lab, Boston, MA 02111 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA. RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Signal Transduct Div, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NHLBI NIH HHS [R01 HL080706-10, R01 HL080706, R01 HL080706-11, R01 HL080706-12, R01 HL080706-13]; NIGMS NIH HHS [GM41890, R01 GM041890, R01 GM054597, R37 GM041890] NR 38 TC 59 Z9 62 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 8 PY 2007 VL 104 IS 19 BP 8077 EP 8082 DI 10.1073/pnas.0702663104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 167OR UT WOS:000246461500062 PM 17483449 ER PT J AU Provot, S Zinyk, D Gunes, Y Kathri, R Le, Q Kronenberg, HM Johnson, RS Longaker, MT Giaccia, AJ Schipani, E AF Provot, Sylvain Zinyk, Dawn Gunes, Yasemin Kathri, Richa Le, Quynh Kronenberg, Henry M. Johnson, Randall S. Longaker, Michael T. Giaccia, Amato J. Schipani, Ernestina TI Hif-1 alpha regulates differentiation of limb bud mesenchyme and joint development SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ENDOCHONDRAL BONE-FORMATION; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ENDOTHELIAL GROWTH-FACTOR; HORMONE-RELATED PEPTIDE; GENE-EXPRESSION; CHONDROCYTE DIFFERENTIATION; HYPERTROPHIC CHONDROCYTES; PROLYL HYDROXYLATION; PARATHYROID-HORMONE; CARTILAGE FORMATION AB Recent evidence suggests that low oxygen tension (hypoxia) may control fetal development and differentiation. A crucial mediator of the adaptive response of cells to hypoxia is the transcription factor Hif-1 alpha In this study, we provide evidence that mesenchymal condensations that give origin to endochondral bones are hypoxic during fetal development, and we demonstrate that Hif-1 alpha is expressed and transcriptionally active in limb bud mesenchyme and in mesenchymal condensations. To investigate the role of Hif-1 alpha in mesenchymal condensations and in early chondrogenesis, we conditionally inactivated Hif-1 alpha in limb bud mesenchyme using a Prx1 promoter-driven Cre transgenic mouse. Conditional knockout of Hif-1 alpha in limb bud mesenchyme does not impair mesenchyme condensation, but alters the formation of the cartilaginous primordia. Late hypertrophic differentiation is also affected as a result of the delay in early chondrogenesis. In addition, mutant mice show a striking impairment of joint development. Our study demonstrates a crucial, and previously unrecognized, role of Hif-1 alpha in early chondrogenesis and joint formation. C1 Stanford Univ, Sch Med, Div Canc & Radiat Biol, Dept Radiat Oncol, Stanford, CA 94305 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA 02114 USA. Univ Calif San Diego, Mol Biol Sect, La Jolla, CA 92093 USA. RP Giaccia, AJ (reprint author), Stanford Univ, Sch Med, Div Canc & Radiat Biol, Dept Radiat Oncol, Stanford, CA 94305 USA. EM Giaccia@stanford.edu OI Johnson, Randall/0000-0002-4084-6639 FU NCI NIH HHS [CA088480, CA67166, P01 CA067166, R01 CA088480, R37 CA088480]; NIAMS NIH HHS [AR048191, R01 AR048191] NR 63 TC 100 Z9 103 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 7 PY 2007 VL 177 IS 3 BP 451 EP 464 DI 10.1083/jcb.200612023 PG 14 WC Cell Biology SC Cell Biology GA 169GF UT WOS:000246580000009 PM 17470636 ER PT J AU Miampamba, M Million, M Yuan, PQ Larauche, M Tache, Y AF Miampamba, Marcel Million, Mulugeta Yuan, Pu-Qing Larauche, Muriel Tache, Yvette TI Water avoidance stress activates colonic myenteric neurons in female rats SO NEUROREPORT LA English DT Article DE colonic motor function; Fos; myenteric neurons; peripheral choline acetyltransferase; stress ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; ENTERIC NERVOUS-SYSTEM; C-FOS EXPRESSION; PARAVENTRICULAR NUCLEUS; GASTROINTESTINAL-TRACT; CONSCIOUS RATS; MOTOR RESPONSE; CRF1 RECEPTOR; SPINAL-CORD AB Stress stimulates colonic motor function and plays a role in functional bowel disorders, prevalently in women. We examined, in conscious female rats, the influence of water avoidance stress for 60 min on colonic myenteric neuron activity using immunohistochemical detection of Fos as a marker of neuronal activity. In control rats, Fos immunoreactive nuclei were rare in proximal and distal colon and no defecation was observed. Water avoidance stimulated fecal pellet output, which was associated with Fos expression in myenteric ganglia of proximal and distal colon including in a population of peripheral choline acetyltransferase-immunoreactive neurons. Atropine blocked fecal pellet output but not Fos expression in myenteric ganglia. These results indicate that psychological stress stimulates the activity of colonic cholinergic myenteric neurons. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Div Digest Dis, David Geffen Sch Med, Ctr Neurovisceral Sci & Womens Hlth,Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Miampamba, M (reprint author), VA Greater Los Angeles Healthcare Syst, Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marcel.miampamba@ferring.com; ytache@mednet.ucla.edu OI Larauche, Muriel/0000-0003-3320-3675 FU NIAMS NIH HHS [P50 AR 049550]; NIDDK NIH HHS [DK 41301, R01 DK 33061] NR 25 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 7 PY 2007 VL 18 IS 7 BP 679 EP 682 DI 10.1097/WNR.0b013e3280bef7f8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 159HK UT WOS:000245856000012 PM 17426598 ER PT J AU Hamik, A Lin, ZY Kumar, A Balcells, M Sinha, S Katz, J Feinberg, MW Gerzsten, RE Edelman, ER Jain, MK AF Hamik, Anne Lin, Zhiyong Kumar, Ajay Balcells, Mercedes Sinha, Sumita Katz, Jonathan Feinberg, Mark W. Gerzsten, Robert E. Edelman, Elazer R. Jain, Mukesh K. TI Kruppel-like factor 4 regulates endothelial inflammation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; KRUPPEL-LIKE FACTOR; NF-KAPPA-B; FINGER TRANSCRIPTION FACTOR; PLASMINOGEN-ACTIVATOR INHIBITOR; ABDOMINAL AORTIC-ANEURYSM; CELL-ADHESION MOLECULE-1; LAMINAR SHEAR-STRESS; GROWTH-FACTOR-BETA; GENE-EXPRESSION AB The vascular endothelium plays a critical role in vascular homeostasis. Inflammatory cytokines and non-laminar blood flow induce endothelial dysfunction and confer a pro-adhesive and pro-thrombotic phenotype. Therefore, identification of factors that mediate the effects of these stimuli on endothelial function is of considerable interest. Kruppel-like factor 4 expression has been documented in endothelial cells, but a function has not been described. In this communication we describe the expression in vitro and in vivo of Kruppel-like factor 4 in human and mouse endothelial cells. Furthermore, we demonstrate that endothelial Kruppel-like factor 4 is induced by pro-inflammatory stimuli and shear stress. Overexpression of Kruppel-like factor 4 induces expression of multiple anti-inflammatory and anti-thrombotic factors including endothelial nitric-oxide synthase and thrombomodulin, whereas knockdown of Kruppel-like factor 4 leads to enhancement of tumor necrosis factor alpha-induced vascular cell adhesion molecule-1 and tissue factor expression. The functional importance of Kruppel-like factor 4 is verified by demonstrating that Kruppel-like factor 4 expression markedly decreases inflammatory cell adhesion to the endothelial surface and prolongs clotting time under inflammatory states. Kruppel-like factor 4 differentially regulates the promoter activity of pro- and anti-inflammatory genes in a manner consistent with its anti-inflammatory function. These data implicate Kruppel-like factor 4 as a novel regulator of endothelial activation in response to pro-inflammatory stimuli. C1 Case Western Reserve Univ, Cardiovasc Res Inst, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc Med, Cambridge, MA 02138 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. Univ Penn, Sch Med, Div Gastroenterol, Dept Med, Philadelphia, PA 19104 USA. RP Jain, MK (reprint author), Case Western Reserve Univ, Cardiovasc Res Inst, Wolstein Res Bldg,2103 Cornell Rd, Cleveland, OH 44106 USA. EM mukesh.jain2@case.edu OI Balcells, Mercedes/0000-0002-2532-0516 FU NHLBI NIH HHS [F32HL078193, HL-69477, HL-72952, HL-75427, HL-76754, P01 HL48743]; PHS HHS [T32 HOLKO 760420] NR 86 TC 156 Z9 163 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 4 PY 2007 VL 282 IS 18 BP 13769 EP 13779 DI 10.1074/jbc.M700078200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 162BC UT WOS:000246060300067 PM 17339326 ER PT J AU Vincent, JL Patel, GH Fox, MD Snyder, AZ Baker, JT Van Essen, DC Zempel, JM Snyder, LH Corbetta, M Raichle, ME AF Vincent, J. L. Patel, G. H. Fox, M. D. Snyder, A. Z. Baker, J. T. Van Essen, D. C. Zempel, J. M. Snyder, L. H. Corbetta, M. Raichle, M. E. TI Intrinsic functional architecture in the anaesthetized monkey brain SO NATURE LA English DT Article ID MACAQUE MONKEY; PARIETAL LOBE; DEFAULT MODE; CONNECTIONS; NETWORKS; CORTEX; ORGANIZATION; DYNAMICS; IMAGES; AREAS AB The traditional approach to studying brain function is to measure physiological responses to controlled sensory, motor and cognitive paradigms. However, most of the brain's energy consumption is devoted to ongoing metabolic activity not clearly associated with any particular stimulus or behaviour(1). Functional magnetic resonance imaging studies in humans aimed at understanding this ongoing activity have shown that spontaneous fluctuations of the blood-oxygen-level-dependent signal occur continuously in the resting state. In humans, these fluctuations are temporally coherent within widely distributed cortical systems that recapitulate the functional architecture of responses evoked by experimentally administered tasks(2-6\). Here, we show that the same phenomenon is present in anaesthetized monkeys even at anaesthetic levels known to induce profound loss of consciousness. We specifically demonstrate coherent spontaneous fluctuations within three well known systems ( oculomotor, somatomotor and visual) and the 'default' system, a set of brain regions thought by some to support uniquely human capabilities. Our results indicate that coherent system fluctuations probably reflect an evolutionarily conserved aspect of brain functional organization that transcends levels of consciousness. C1 Washington Univ, Dept Radiol, St Louis, MO 63110 USA. Washington Univ, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Washington Univ, Dept Biomed Engn, St Louis, MO 63110 USA. Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Raichle, ME (reprint author), Washington Univ, Dept Radiol, St Louis, MO 63110 USA. EM marc@npg.wustl.edu RI Vincent, Justin/B-5033-2012; Snyder, Lawrence/A-4593-2017 NR 33 TC 845 Z9 863 U1 6 U2 63 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 3 PY 2007 VL 447 IS 7140 BP 83 EP U4 DI 10.1038/nature05758 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 163GY UT WOS:000246149300048 PM 17476267 ER PT J AU Reese, TA Liang, HE Tager, AM Luster, AD Van Rooijen, N Voehringer, D Locksley, RM AF Reese, Tiffany A. Liang, Hong-Erh Tager, Andrew M. Luster, Andrew D. Van Rooijen, Nico Voehringer, David Locksley, Richard M. TI Chitin induces accumulation in tissue of innate immune cells associated with allergy SO NATURE LA English DT Article ID ACIDIC MAMMALIAN CHITINASE; TYPE-2 IMMUNITY; LEUKOTRIENE B-4; IN-VIVO; RECEPTOR; MACROPHAGES; GENE; CHITOTRIOSIDASE; IDENTIFICATION; INFLAMMATION AB Allergic and parasitic worm immunity is characterized by infiltration of tissues with interleukin (IL)-4- and IL-13-expressing cells, including T-helper-2 cells, eosinophils and basophils(1). Tissue macrophages assume a distinct phenotype, designated alternatively activated macrophages(2). Relatively little is known about the factors that trigger these host responses. Chitin, a widespread environmental biopolymer of N-acetyl-beta-D-glucosamine, provides structural rigidity to fungi, crustaceans, helminths and insects(3). Here, we show that chitin induces the accumulation in tissue of IL-4- expressing innate immune cells, including eosinophils and basophils, when given to mice. Tissue infiltration was unaffected by the absence of Toll-like-receptor-mediated lipopolysaccharide recognition but did not occur if the injected chitin was pre-treated with the IL-4- and IL-13-inducible mammalian chitinase, AMCase(4), or if the chitin was injected into mice that overexpressed AMCase. Chitin mediated alternative macrophage activation in vivo and the production of leukotriene B-4, which was required for optimal immune cell recruitment. Chitin is a recognition element for tissue infiltration by innate cells implicated in allergic and helminth immunity and this process can be negatively regulated by a vertebrate chitinase. C1 Univ Calif San Francisco, Howard Hughes Med Inst, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Howard Hughes Med Inst, Dept Immunol Microbiol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Vrije Univ Amsterdam, Dept Mol Cell Biol, NL-1091 BT Amsterdam, Netherlands. RP Locksley, RM (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Med, San Francisco, CA 94143 USA. EM locksley@medicine.ucsf.edu FU NIAID NIH HHS [R01 AI030663, R01 AI026918, R37 AI026918, R37 AI026918-20] NR 31 TC 394 Z9 409 U1 7 U2 53 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 3 PY 2007 VL 447 IS 7140 BP 92 EP U7 DI 10.1038/nature05746 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 163GY UT WOS:000246149300050 PM 17450126 ER PT J AU Hughes, ME Bortnick, R Tsubouchi, A Baumer, P Kondo, M Uemura, T Schmucker, D AF Hughes, Michael E. Bortnick, Rachel Tsubouchi, Asako Baumer, Philipp Kondo, Masahiro Uemura, Tadashi Schmucker, Dietmar TI Homophilic Dscam interactions control complex dendrite morphogenesis SO NEURON LA English DT Article ID DROSOPHILA SENSORY NEURONS; AXON GUIDANCE; MOLECULAR DIVERSITY; RECEPTOR; REPULSION; BRANCHES; DOCK; PAK; CNS AB Alternative splicing of the Drosophila gene Dscam results in up to 38,016 different receptor isoforms proposed to interact by isoform-specific homophilic binding. We report that Dscam controls cell-intrinsic aspects of dendrite guidance in all four classes of dendrite arborization (da) neurons. Loss of Dscam in single neurons causes a strong increase in self-crossing. Restriction of dendritic fields of neighboring class III neurons appeared intact in mutant neurons, suggesting that dendritic self-avoidance, but not heteroneuronal tiling, may depend on Dscam. Overexpression of the same Dscam isoforms in two da neurons with overlapping dendritic fields forced a spatial segregation of the two fields, supporting the model that dendritic branches of da neurons use isoform-specific homophilic interactions to ensure minimal overlap. Homophilic binding of the highly diverse extracellular domains of Dscam may therefore limit the use of the same "core" repulsion mechanism to cell-intrinsic interactions without interfering with heteroneuronal interactions. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Kyoto Univ, Grad Sch Biostudies, Kyoto 6068501, Japan. RP Schmucker, D (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM dietmar_schmucker@dfci.harvard.edu OI UEMURA, Tadashi/0000-0001-7204-3606 FU NINDS NIH HHS [R01 NS046747, R01 NS046747-02, R01-NS46747, R01 NS046747-01, R01 NS046747-04, R01 NS046747-03] NR 27 TC 134 Z9 136 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY 3 PY 2007 VL 54 IS 3 BP 417 EP 427 DI 10.1016/j.neuron.2007.04.013 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 173EG UT WOS:000246855700012 PM 17481395 ER PT J AU Genuth, S Nathan, DM Zinman, B Crofford, O Crandall, J Phillips, M Reid, M Brown-Friday, J Engel, S Sheindlin, J Martinez, H Shamoon, H Engel, H Dahms, W Palmert, M Mayer, L Pendegras, S Zegarra, H Miller, D Singerman, L Smith-Brewer, S Gubitosi-Klug, R Gaston, P Genuth, S Brillon, D Lackaye, ME Reppucci, V Lee, T Heinemann, M Whitehouse, F McLellan, M Kruger, D Carey, JD Angus, E Croswell, M Galpirn, A Bergenstal, R Johnson, M Spencer, M Morgan, K Etzwiler, D Kendall, D Noller, D Jacobson, A Golden, E Beaser, R Ganda, O Hamdy, O Rosenzweig, J Wolpert, H Sharuk, PG Arrigg, P Burwood, A Rand, L Nathan, DM Larkin, M Godine, J Moore, D Cagliero, E Lou, P Fritz, S Service, J Ziegler, G Pach, J Colligan, R Lopes-Virella, M Colwell, J Hermayer, K Brabham, M Soule, J Belvins, A Parker, J Lee, D Lindsey, P Bracey, M Lee, K Farr, A Elsing, S Thompson, T Selby, J Lyons, T Yacoub-Wasef, S Szpiech, M Wood, D Mayfield, R Molitch, M Schaefer, B Jampol, L Lyon, A Gill, M Mathura, J Strugula, Z Kaminski, L Shankle, J Astlesford, P Blackburn, D Ajroud-Driss, S Stone, O West, C Burnett-Zeigler, I Weinberg, D Kolterman, O Lorenzi, G Goldbaum, M Sivitz, W Bayless, M Weingeist, T Stone, E Boldt, HC Gehres, K Russell, S Bayless, J Kramer, J Long, J Zeither, R Hebdon, M Donner, T Johnsonbaugh, S Gordon, J Kowarski, A Ostrowski, D Donner, T Steidl, S Jones, B Counts, D Herman, W Martin, C Pop-Busui, R Vine, AK Elner, S Feldman, E Albers, J Greene, D Stevens, MJ Bantle, J Rogness, B Olsen, T Steuer, E Rath, P Johnston, R Hainsworth, D Hitt, S Giangiacom, J Goldstein, D Schade, D Canady, J Burge, M Schluter, JM Das, A Hornbeck, D Schwartz, S Bourne, PA Maschak-Carey, BJ Baker, L Braunstein, S Brucker, A Orchard, T Silvers, N Ryan, C Songer, T Doft, B Olson, S Bergren, RL Lobes, L Fineman, M Freisberg, L Lobes, L Rath, PP Becker, D Drash, A Morrison, A Vaccaro-Kish, J Bernal, ML Malone, J Pavan, PR Grove, N Iyer, MN Burrows, AF Tanaka, EA Berger, C Gstalder, R Dagogo-Jack, S Wigley, C Ricks, H Kitabchi, A Murphy, MB Moser, S Meyer, D Iannacone, A Chaum, E Bryer-Ash, M Schussler, S Lambeth, H Raskin, P Strowig, S He, YG Edwards, A Alappatt, J Wilson, C Park, S Zinman, B Barnie, A MacLean, S Devenyi, R Mandelcorn, M Brent, M Rogers, S Gordon, A Palmer, J Catton, S Brunzell, J Ginsberg, J Kinyoun, J Van Ottingham, L Dupre, J Harth, J Nicolle, D Canny, C May, M Lipps, J Agarwal, A Adkins, T Survant, L Lorenz, R Feman, S White, N Levandoski, L Boniuk, I Grand, G Thomas, M Burgess, D Joseph, D Blinder, K Shah, G Santiago, J Tamborlane, W Gatcomb, P Stoessel, K Taylor, K Dahms, W Trail, R Quin, J Gaston, P Palmert, M Lachin, J Cleary, P Kenny, D Backlund, J Sun, W Rutledge, B Waberski, B Klumpp, K Chan, K Diminick, L Rosenberg, D Petty, B Determan, A Williams, C Dews, L Hawkins, M Cowie, C Fradkin, J Siebert, C Eastman, R Danis, R Davis, M Hubbard, L Geithman, P Kastorff, L Neider, M Badal, D Esser, B Miner, K Wabers, H Glander, K Joyce, J Robinson, N Hurtenbach, C Hannon, C Steffes, M Bucksa, J Chavers, B O'Leary, D Funk, L Polak, J Harrington, A Crow, R Gloeb, B Thomas, S O'Donnell, C Prineas, R Campbell, C Ryan, C Sandstrom, D Williams, T Geckle, M Cupelli, E Thoma, F Burzuk, B Woodfill, T Low, P Sommer, C Nickander, K Detrano, R Wong, N Fox, M Kim, L Oudiz, R Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Manolio, T Rand, L Singer, D Stern, M Lopes-Virella, M Garvey, WT Lyons, TJ Jenkins, A Klein, R Virella, G Jaffa, AA Lackland, D Brabham, M Mcgee, D Zheng, D Mayfield, RK Paterson, A Boright, A Bull, S Sun, L Scherer, S Zinman, B Brunzell, J Hokanson, J Marcovina, S Purnell, J Sibley, S Deeb, S Edwards, K Manning, C Ruocco, A Tinker, J Thomas, JL Shikhman, M Krishnamurthy, L Scott, S Baines, T Wong, B Nakash, O Baity, M Kotyk-Sellnow, S Swenson, S Devine, D Meyer, T Khanna, M Dreyer, S Randal, D Scott, S Kramer, J Bayless, J Kraft, C Welnel, S Swisher, S Pramuka, M Murphy, L Hunter, C Shaw, J Montague, E Scully, J Roger, M Gouchie, C Folley, B Perantie, D Warren, S Dorr, C Cuglietto, D Stone, O Boyd, C Spencer, R Kernen, S Wells, K Yanover, T Spencer, A Nathan, DM AF Genuth, S. Nathan, D. M. Zinman, B. Crofford, O. Crandall, J. Phillips, M. Reid, M. Brown-Friday, J. Engel, S. Sheindlin, J. Martinez, H. Shamoon, H. Engel, H. Dahms, W. Palmert, M. Mayer, L. Pendegras, S. Zegarra, H. Miller, D. Singerman, L. Smith-Brewer, S. Gubitosi-Klug, R. Gaston, P. Genuth, S. Brillon, D. Lackaye, M. E. Reppucci, V. Lee, T. Heinemann, M. Whitehouse, F. McLellan, M. Kruger, D. Carey, J. D. Angus, E. Croswell, M. Galpirn, A. Bergenstal, R. Johnson, M. Spencer, M. Morgan, K. Etzwiler, D. Kendall, D. Noller, D. Jacobson, A. Golden, E. Beaser, R. Ganda, O. Hamdy, O. Rosenzweig, J. Wolpert, H. Sharuk, P. G. Arrigg, P. Burwood, A. Rand, L. Nathan, D. M. Larkin, M. Godine, J. Moore, D. Cagliero, E. Lou, P. Fritz, S. Service, J. Ziegler, G. Pach, J. Colligan, R. Lopes-Virella, M. Colwell, J. Hermayer, K. Brabham, M. Soule, J. Belvins, A. Parker, J. Lee, D. Lindsey, P. Bracey, M. Lee, K. Farr, A. Elsing, S. Thompson, T. Selby, J. Lyons, T. Yacoub-Wasef, S. Szpiech, M. Wood, D. Mayfield, R. Molitch, M. Schaefer, B. Jampol, L. Lyon, A. Gill, M. Mathura, J. Strugula, Z. Kaminski, L. Shankle, J. Astlesford, P. Blackburn, D. Ajroud-Driss, S. Stone, O. West, C. Burnett-Zeigler, I. Weinberg, D. Kolterman, O. Lorenzi, G. Goldbaum, M. Sivitz, W. Bayless, M. Weingeist, T. Stone, E. Culver Boldt, H. Gehres, K. Russell, S. Bayless, J. Kramer, J. Long, J. Zeither, R. Hebdon, M. Donner, T. Johnsonbaugh, S. Gordon, J. Kowarski, A. Ostrowski, D. Donner, T. Steidl, S. Jones, B. Counts, D. Herman, W. Martin, C. Pop-Busui, R. Vine, A. K. Elner, S. Feldman, E. Albers, J. Greene, D. Stevens, M. J. Bantle, J. Rogness, B. Olsen, T. Steuer, E. Rath, P. Johnston, R. Hainsworth, D. Hitt, S. Giangiacom, J. Goldstein, D. Schade, D. Canady, J. Burge, M. Schluter, J. M. Das, A. Hornbeck, D. Schwartz, S. Bourne, P. A. Maschak-Carey, B. J. Baker, L. Braunstein, S. Brucker, A. Orchard, T. Silvers, N. Ryan, C. Songer, T. Doft, B. Olson, S. Bergren, R. L. Lobes, L. Fineman, M. Freisberg, L. Lobes, L. Paczan Rath, P. Becker, D. Drash, A. Morrison, A. Vaccaro-Kish, J. Bernal, M. L. Malone, J. Pavan, P. R. Grove, N. Iyer, M. N. Burrows, A. F. Tanaka, E. A. Berger, C. Gstalder, R. Dagogo-Jack, S. Wigley, C. Ricks, H. Kitabchi, A. Murphy, M. B. Moser, S. Meyer, D. Iannacone, A. Chaum, E. Bryer-Ash, M. Schussler, S. Lambeth, H. Raskin, P. Strowig, S. He, Y. -G. Edwards, A. Alappatt, J. Wilson, C. Park, S. Zinman, B. Barnie, A. MacLean, S. Devenyi, R. Mandelcorn, M. Brent, M. Rogers, S. Gordon, A. Palmer, J. Catton, S. Brunzell, J. Ginsberg, J. Kinyoun, J. Van Ottingham, L. Dupre, J. Harth, J. Nicolle, D. Canny, C. May, M. Lipps, J. Agarwal, A. Adkins, T. Survant, L. Lorenz, R. Feman, S. White, N. Levandoski, L. Boniuk, I. Grand, G. Thomas, M. Burgess, D. Joseph, D. Blinder, K. Shah, G. Santiago, J. Tamborlane, W. Gatcomb, P. Stoessel, K. Taylor, K. Dahms, W. Trail, R. Quin, J. Gaston, P. Palmert, M. Lachin, J. Cleary, P. Kenny, D. Backlund, J. Sun, W. Rutledge, B. Waberski, B. Klumpp, K. Chan, K. Diminick, L. Rosenberg, D. Petty, B. Determan, A. Williams, C. Dews, L. Hawkins, M. Cowie, C. Fradkin, J. Siebert, C. Eastman, R. Danis, R. Davis, M. Hubbard, L. Geithman, P. Kastorff, L. Neider, M. Badal, D. Esser, B. Miner, K. Wabers, H. Glander, K. Joyce, J. Robinson, N. Hurtenbach, C. Hannon, C. Steffes, M. Bucksa, J. Chavers, B. O'Leary, D. Funk, L. Polak, J. Harrington, A. Crow, R. Gloeb, B. Thomas, S. O'Donnell, C. Prineas, R. Campbell, C. Ryan, C. Sandstrom, D. Williams, T. Geckle, M. Cupelli, E. Thoma, F. Burzuk, B. Woodfill, T. Low, P. Sommer, C. Nickander, K. Detrano, R. Wong, N. Fox, M. Kim, L. Oudiz, R. Weir, G. Clark, C. D'Agostino, R. Espeland, M. Klein, B. Manolio, T. Rand, L. Singer, D. Stern, M. Lopes-Virella, M. Garvey, W. T. Lyons, T. J. Jenkins, A. Klein, R. Virella, G. Jaffa, A. A. Lackland, D. Brabham, M. McGee, D. Zheng, D. Mayfield, R. K. Paterson, A. Boright, A. Bull, S. Sun, L. Scherer, S. Zinman, B. Brunzell, J. Hokanson, J. Marcovina, S. Purnell, J. Sibley, S. Deeb, S. Edwards, K. Manning, C. Ruocco, A. Tinker, J. Thomas, J. L. Shikhman, M. Krishnamurthy, L. Scott, S. Baines, T. Wong, B. Nakash, O. Baity, M. Kotyk-Sellnow, S. Swenson, S. Devine, D. Meyer, T. Khanna, M. Dreyer, S. Randal, D. Scott, S. Kramer, J. Bayless, J. Kraft, C. Welnel, S. Swisher, S. Pramuka, M. Murphy, L. Hunter, C. Shaw, J. Montague, E. Scully, J. Roger, M. Gouchie, C. Folley, B. Perantie, D. Warren, S. Dorr, C. Cuglietto, D. Stone, O. Boyd, C. Spencer, R. Kernen, S. Wells, K. Yanover, T. Spencer, A. Nathan, D. M. CA DCCT EDIC Study Res Grp TI Long-term effect of diabetes and its treatment on cognitive function SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SEVERE HYPOGLYCEMIA; COMPLICATIONS TRIAL; INSULIN-TREATMENT; NORMATIVE DATA; IDDM PATIENTS; BRAIN-DAMAGE; PERFORMANCE; INTERVENTIONS; EPIDEMIOLOGY; DYSFUNCTION AB BACKGROUND: Long-standing concern about the effects of type 1 diabetes on cognitive ability has increased with the use of therapies designed to bring glucose levels close to the nondiabetic range and the attendant increased risk of severe hypoglycemia. METHODS: A total of 1144 patients with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study were examined on entry to the DCCT (at mean age 27 years) and a mean of 18 years later with the same comprehensive battery of cognitive tests. Glycated hemoglobin levels were measured and the frequency of severe hypoglycemic events leading to coma or seizures was recorded during the follow-up period. We assessed the effects of original DCCT treatment-group assignment, mean glycated hemoglobin values, and frequency of hypoglycemic events on measures of cognitive ability, with adjustment for age at baseline, sex, years of education, length of follow-up, visual acuity, self-reported sensory loss due to peripheral neuropathy, and (to control for the effects of practice) the number of cognitive tests taken in the interval since the start of the DCCT. RESULTS: Forty percent of the cohort reported having had at least one hypoglycemic coma or seizure. Neither frequency of severe hypoglycemia nor previous treatment-group assignment was associated with decline in any cognitive domain. Higher glycated hemoglobin values were associated with moderate declines in motor speed (P=0.001) and psychomotor efficiency (P < 0.001), but no other cognitive domain was affected. CONCLUSIONS: No evidence of substantial long-term declines in cognitive function was found in a large group of patients with type 1 diabetes who were carefully followed for an average of 18 years, despite relatively high rates of recurrent severe hypoglycemia. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. George Washington Univ, Rockville, MD USA. Univ Iowa, Coll Med, Iowa City, IA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Western Ontario, Schulich Sch Med, London, ON, Canada. RP Genuth, S (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. RI Zinman, Bernard/E-7266-2013 NR 41 TC 257 Z9 261 U1 0 U2 34 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 3 PY 2007 VL 356 IS 18 BP 1842 EP 1852 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 163CL UT WOS:000246136200006 ER PT J AU Wong, KK Maser, RS Sahin, E Bailey, ST Xia, H Ji, H McNamara, K Naylor, M Bronson, RT Ghosh, S Welsh, R DePinho, RA AF Wong, K-K Maser, R. S. Sahin, E. Bailey, S. T. Xia, H. Ji, H. McNamara, K. Naylor, M. Bronson, R. T. Ghosh, S. Welsh, R. DePinho, R. A. TI Diminished lifespan and acute stress-induced death in DNA-PKcs-deficient mice with limiting telomeres SO ONCOGENE LA English DT Article DE DNAPKcs; telomere; telomerase; stress; aging; cytokines ID NF-KAPPA-B; ACTIVATION; REPAIR; AGE; KU; RESTRICTION; MAINTENANCE; DYSFUNCTION; IMMUNITY; LACKING AB An adequate and appropriate response to physiological and pathophysiological stresses is critical for long-term homeostasis and viability of the aging organism. Previous work has pointed to the immune system, telomeres and DNA repair pathways as important and distinct determinants of a normal healthy lifespan. In this study, we explored the genetic interactions of telomeres and DNA-PKcs, a protein involved in non-homologous end-joining (NHEJ) and immune responses, in the context of a key aspect of aging and lifespan - the capacity to mount an acute and appropriate immune-mediated stress response. We observed that the combination of DNA-PKcs deficiency and telomere dysfunction resulted in a shortened lifespan that was reduced further following viral infection or experimental activation of the innate immune response. Analysis of the innate immune response in the DNA-PKcs-deficient mice with short dysfunctional telomeres revealed high basal serum levels of tumor necrosis factor alpha (TNF alpha) and hyper-active cytokine responses upon challenge with polyinosinic-polycytidylic acid (poly-IC). We further show that serum cytokine levels become elevated in telomere dysfunctional mice as a function of age. These results raise speculation that these genetic factors may contribute to misdirected immune responses of the aged under conditions of acute and chronic stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA. Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Belfer Fdn Inst Innovat Canc Sci, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M413, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu RI Maser, Richard/B-2970-2012; Bailey, Shannon/B-8045-2014 FU NCI NIH HHS [CA34461, P01 CA95616, R01 CA84628, U01 CA84313]; NIA NIH HHS [K08 AG2400401] NR 24 TC 2 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 3 PY 2007 VL 26 IS 20 BP 2815 EP 2821 DI 10.1038/sj.onc.1210099 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 164CR UT WOS:000246210800001 PM 17072335 ER PT J AU Ogino, S Kawasaki, T Kirkner, GJ Ohnishi, M Fuchs, CS AF Ogino, Shuji Kawasaki, Takako Kirkner, Gregory J. Ohnishi, Mutsuko Fuchs, Charles S. TI 18q loss of heterozygosity in microsatellite stable colorectal cancer is correlated with CpG island methylator phenotype-negative (CIMP-0) and inversely with CIMP-low and CIMP-high SO BMC CANCER LA English DT Article ID COLON-CANCER; DNA METHYLATION; CHROMOSOMAL INSTABILITY; ALLELIC LOSS; GENOMIC INSTABILITY; BRAF MUTATION; DEMETHYLATION; KRAS; CARCINOGENESIS; PREDICTORS AB Background: The CpG island methylator phenotype ( CIMP) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer, associated with microsatellite instability-high ( MSI-high) and BRAF mutations. 18q loss of heterozygosity ( LOH) commonly present in colorectal cancer with chromosomal instability ( CIN) is associated with global hypomethylation in tumor cell. A recent study has shown an inverse correlation between CIN and CIMP ( determined by MINTs, p16, p14 and MLH1 methylation) in colorectal cancer. However, no study has examined 18q LOH in relation to CIMP-high, CIMP-low ( less extensive promoter methylation) and CIMP-0 ( CIMP-negative), determined by quantitative DNA methylation analysis. Methods: Utilizing MethyLight technology ( real-time PCR), we quantified DNA methylation in 8 CIMP-specific promoters {CACNA1G, CDKN2A ( p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1} in 758 non-MSI-high colorectal cancers obtained from two large prospective cohorts. Using four 18q microsatellite markers ( D18S55, D18S56, D18S67 and D18S487) and stringent criteria for 18q LOH, we selected 374 tumors ( 236 LOH-positive tumors with = 2 markers showing LOH; and 138 LOH-negative tumors with = 3 informative markers and no LOH). Results: CIMP-0 ( 0/8 methylated promoters) was significantly more common in 18q LOH-positive tumors ( 59% = 139/236, p = 0.002) than 18q LOH-negative tumors ( 44% = 61/138), while CIMP-low/high ( 1/8 - 8/8 methylated promoters) was significantly more common ( 56%) in 18q LOH-negative tumors than 18q LOH-positive tumors ( 41%). These relations persisted after stratification by sex, location, or the status of MSI, p53 expression ( by immunohistochemistry), or KRAS/BRAF mutation. Conclusion: 18q LOH is correlated positively with CIMP-0 and inversely with CIMP-low and CIMP-high. Our findings provide supporting evidence for relationship between CIMP-0 and 18q LOH as well as a molecular difference between CIMP-0 and CIMP-low in colorectal cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Ogino, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu; takako_kawasaki@dfci.harvard.edu; gregory.kirkner@channing.harvard.edu; mutsuko_ohnishi@dfci.harvard.edu; charles_fuchs@dfci.harvard.edu FU NCI NIH HHS [P01 CA55075, P01 CA055075, P01 CA087969, P01 CA87969] NR 44 TC 34 Z9 35 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAY 2 PY 2007 VL 7 AR 72 DI 10.1186/1471-2407-7-72 PG 9 WC Oncology SC Oncology GA 171AY UT WOS:000246708500001 PM 17474983 ER PT J AU Rodrigues, MS Sattler, M AF Rodrigues, Margret S. Sattler, Martin TI Chronic myelogenous leukemia progenitors display a genetically unstable personality SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CHRONIC MYELOID-LEUKEMIA; COMPLETE CYTOGENETIC REMISSION; IMATINIB MESYLATE TREATMENT; REACTIVE OXYGEN; ABL GENE; RESISTANCE; MUTATIONS; CANCER; REPAIR; CELLS C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM martin_sattler@dfci.harvard.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 2 PY 2007 VL 99 IS 9 BP 662 EP 663 DI 10.1093/jnci/djk176 PG 2 WC Oncology SC Oncology GA 166BQ UT WOS:000246352500002 PM 17470729 ER PT J AU Ginde, AA Delaney, KE Lieberman, RM Vanderweil, SG Camargo, CA AF Ginde, Adit A. Delaney, Kate E. Lieberman, Rebecca M. Vanderweil, Stefan G. Camargo, Carlos A., Jr. TI Estimated risk for undiagnosed diabetes in the emergency department: A multicenter survey SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE diabetes mellitus; risk factors; screening; emergency medicine ID GLUCOSE AB Background: One third of the 21 million Americans with diabetes remain undiagnosed. The emergency department (ED) is a novel setting for diabetes screening. Objectives: To estimate risk factors for undiagnosed diabetes in the ED. Methods: This was a cross sectional survey in five Boston EDs. The authors enrolled consecutive adults without known diabetes over two 24-hour periods at each site. The focus was on diabetes risk factors and estimated risk for diabetes on the basis of American Diabetes Association (ADA) criteria. The authors also examined prior diabetes testing and willingness to participate in ED-based diabetes screening. Results: Six hundred four patients (70% of eligible) were enrolled. On the basis of ADA risk score, 33% (95% confidence interval [CI] = 29% to 37%) were high risk for undiagnosed diabetes, and an additional 42% (95% CI = 38% to 46%) had elevated risk. For example, 58% (95% CI = 54% to 62%) of participants were overweight or obese (body mass index of >= 25). Among these at-risk participants without prior diabetes testing, 73% (95% CI = 66% to 80%) reported amenability to having additional blood drawn for ED diabetes screening, and 98% (95% CI = 96% to 100%) indicated that they would follow up for confirmation of abnormal screening. Conclusions: Many ED patients in the study had risk factors for undiagnosed diabetes. Patient attitudes toward ED-based diabetes screening support further exploration of this important and currently underutilized opportunity for public health intervention. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. EM ccamargo@partners.org RI Siry, Bonnie/D-7189-2017 NR 10 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 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAY PY 2007 VL 14 IS 5 BP 492 EP 495 DI 10.1197/j.aem.2006.12.017 PG 4 WC Emergency Medicine SC Emergency Medicine GA 160RN UT WOS:000245960100020 PM 17392521 ER PT J AU Shields, HM Guss, D Somers, SC Kerfoot, BP Mandell, BS Travassos, WJ Ullman, SM Maroo, S Honan, JP Raymond, LW Goldberg, EM Leffler, DA Hayward, JN Pelletier, SR Carbo, AR Fishman, LN Nath, BJ Cohn, MA Hafler, JP AF Shields, Helen M. Guss, Daniel Somers, Samuel C. Kerfoot, B. Price Mandell, Brian S. Travassos, Win J. Ullman, Sonal M. Maroo, Seema Honan, James P. Raymond, Laurie W. Goldberg, Eric M. Leffler, Daniel A. Hayward, Jane N. Pelletier, Stephen R. Carbo, Alexander R. Fishman, Laurie N. Nath, Barbara J. Cohn, Michele A. Hafler, Janet P. TI A faculty development program to train tutors to be discussion leaders rather than facilitators SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Essential Elements of a Successful Gastrointestinal Pathophysiology Course CY 2005 CL Chicago, IL SP Amer Gastroenterol Assoc, Educ Comm ID OUTCOMES AB Purpose During 2003, 2004, and 2005, the role of 70 tutors was changed from that of facilitator to discussion leader, in a preclinical PBL learning course, Gastrointestinal Pathophysiology, by use of three key business school teaching strategies: questions, summaries, and schematics. The purpose of this study was to learn what difference this new approach made. Method During each of the three study years, 171 (2003), 167 (2004), and 170 (2005) students were given Likert-scale attitudinal questionnaires to rate whether their tutors encouraged student direction of the tutorials and whether the summaries and closure schematics benefited their learning. Students' overall course evaluations and mean USMLE scores were quantitatively analyzed, pre- and postintervention. A variety of statistical tests were used to assess the statistical significance of means at the confidence level of .05. Results in the third year of the program, student ratings indicated that their tutors were significantly better at encouraging student direction of the tutorials than in the first year (P <.05). The students reported that the tutorial made a more important contribution to their learning (P <.05), and the course objectives were better stated (P =.038) and better met (P =.007). Overall satisfaction with the course also improved significantly (P =.006). Part I gastrointestinal system mean scores of the USMLE showed a statistically significant increase in 2005 compared with 2001 or 2002. Conclusions The tutor as a discussion leader who questions, summarizes, and uses schematics to illustrate concepts had a significant and positive impact on learning in tutorials, achieving course objectives, improving overall course satisfaction, and increasing a standardized national exam's mean score. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. Concord Gastroenterol, Concord, NH USA. Vet Adm Boston Hlth Care Syst, Jamaica Plain, MA USA. Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Program Med Educ, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gen Med, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Fac Dev, Boston, MA 02115 USA. RP Shields, HM (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Rabb 420,330 Brookline Ave, Boston, MA 02215 USA. EM hshields@bidmc.harvard.edu NR 15 TC 16 Z9 19 U1 0 U2 4 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 MAY PY 2007 VL 82 IS 5 BP 486 EP 492 DI 10.1097/ACM.0b013e31803eac9f PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 163PJ UT WOS:000246171800011 PM 17457073 ER PT J AU Stanton, RC Mayer, LD Oriol, NE Treadway, KK Tosteson, DC AF Stanton, Robert C. Mayer, Lisa D. Oriol, Nancy E. Treadway, Katharine K. Tosteson, Daniel C. TI The Mentored Clinical Casebook Project at Harvard Medical School SO ACADEMIC MEDICINE LA English DT Article ID PORTFOLIOS; STUDENTS; SCIENCE AB An excellent physician must be aware of the countless issues that affect each patient's health. Many medical education programs expose students to a broad spectrum of disparate knowledge and hope they will integrate all the pieces into a coherent whole. The authors describe an explicit approach to integration used at Harvard Medical School since 2003 that aims to enhance students' learning in medical school and throughout their medical careers: the Mentored Clinical Casebook Project (MCCP). The MCCP is constructed on the premise that such integration does not occur suddenly but, rather, is an unending process. A first-year student is assigned to one clinician and follows one patient for one year. The student is expected to spend as much time with the patient as possible, in both clinical and nonclinical settings, seek help from the clinician, and consult other experts and sources to develop a complete picture of the patient's life. The student must produce a casebook that includes, but is not limited to, the patient's history, basic science, clinical, socioeconomic, and cultural issues; and self-reflection. The MCCP is intended to allow students to develop a deeper and more diverse understanding of what comprises a patient's health care life, to discern the patient as a person and the person as a patient. This educational project has been popular with students since its inception, providing them with a personal framework from which to address the needs of future patients and introducing them to how much they will continue to learn from their patients. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Renal Sect, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Renal Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM robert.stanton@joslin.harvard.edu NR 12 TC 1 Z9 1 U1 0 U2 1 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 MAY PY 2007 VL 82 IS 5 BP 516 EP 520 DI 10.1097/ACM.0b013e31803eaed9 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 163PJ UT WOS:000246171800015 PM 17457078 ER PT J AU Nolen, WA Kupka, RW Hellemann, G Frye, MA Altshuler, LL Leverich, GS Suppes, T Keck, PE McElroy, S Grunze, H Mintz, J Post, RM AF Nolen, W. A. Kupka, R. W. Hellemann, G. Frye, M. A. Altshuler, L. L. Leverich, G. S. Suppes, T. Keck, P. E., Jr. McElroy, S. Grunze, H. Mintz, J. Post, R. M. TI Tranylcypromine vs. lamotrigine in the treatment of refractory bipolar depression: a failed but clinically useful study SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE bipolar disorder; bipolar depression; tranylcypromine; lamotrigine; lithium; anticonvulsant ID MOOD STABILIZERS; MAINTENANCE TREATMENT; VENLAFAXINE; DISORDER; MANIA; ANTIDEPRESSANTS; IMIPRAMINE; SERTRALINE; BUPROPION; CROSSOVER AB Objective: To compare the efficacy and tolerability of tranylcypromine vs. lamotrigine in bipolar depression not responding to conventional antidepressants. Method: Bipolar depressed patients received open randomized treatment with tranylcypromine or lamotrigine as add-on to a mood stabilizer during 10 weeks. In a second treatment phase, non-responding patients could receive the opposite drug. Outcome criteria were response (measured with CGI-BP and IDS-C), switch into mania, and completion of the study. Results: Only 20 of 70 planned patients were randomized, due to problems with recruitment, and 19 patients received any medication. During the first treatment phase 5/8 patients (62.5%) responded to tranylcypromine without switch into mania, compared with 4/11 patients (36.4%) on lamotrigine with two switches (statistically not significant). Over both treatment phases, 8/10 patients (80%) receiving tranylcypromine completed the study vs. 5/13 (38.5%) on lamotrigine (likelihood 0.02). Conclusions: There still appears to be a role for tranylcypromine in the treatment of refractory bipolar depression. Larger controlled studies are demanded. C1 Univ Groningen, Dept Psychiat, Univ Med Ctr Groningen, NL-9700 RB Groningen, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. NIMH, Dept Hlth & Human Serv, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH USA. Univ Munich, Munich, Germany. RP Nolen, WA (reprint author), Univ Groningen, Dept Psychiat, Univ Med Ctr Groningen, POB 30-001, NL-9700 RB Groningen, Netherlands. EM w.a.nolen@med.umcg.nl RI Nolen, Willem/E-9006-2014; OI Grunze, Heinz/0000-0003-4712-8979 NR 23 TC 30 Z9 31 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD MAY PY 2007 VL 115 IS 5 BP 360 EP 365 DI 10.1111/j.1600-0447.2007.00993.x PG 6 WC Psychiatry SC Psychiatry GA 152VM UT WOS:000245390100004 PM 17430413 ER PT J AU Tyrka, AR Wier, LM Anderson, GM Wilkinson, CW Price, LH Carpenter, LL AF Tyrka, A. R. Wier, L. M. Anderson, G. M. Wilkinson, C. W. Price, L. H. Carpenter, L. L. TI Temperament and response to the trier social stress test SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE Cortisol; adrenocorticotropic hormone; stress; temperament; personality; inhibition ID TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; CORTICOTROPIN-RELEASING FACTOR; BEHAVIORAL-INHIBITION; PSYCHOBIOLOGICAL MODEL; FEARFUL TEMPERAMENT; CORTISOL RESPONSES; SALIVARY CORTISOL; MAJOR DEPRESSION; PHYSICAL ABUSE; RHESUS-MONKEYS AB Objective: The personality characteristics behavioural inhibition and neuroticism have been associated with mood and anxiety disorders and, in some studies, hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We recently reported that low levels of Novelty Seeking were associated with elevated plasma cortisol responses to the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test in healthy adults with no psychiatric disorder. The present study tested the association between temperament and HPA axis function in the same group of subjects using a standardized psychosocial neuroendocrine stress test. Method: Subjects completed diagnostic interviews, questionnaires, and the Trier Social Stress Test (TSST). Results: Novelty Seeking was inversely associated with plasma cortisol concentrations at baseline and throughout the TSST, but was not related to adrenocorticotropic hormone (ACTH) levels. Conclusion: Results of this study extend our previous finding in the Dex/CRH test to a psychosocial stress test. Future investigations are needed to replicate these findings and further elucidate how temperament and personality are linked to HPA function. C1 Butler Hosp, Mood Disorders Res Program, Providence, RI 02906 USA. Butler Hosp, Lab Clin Neurosci, Providence, RI 02906 USA. Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Tyrka, AR (reprint author), Butler Hosp, Mood Disorders Res Program, 345 Blackstone Blvd, Providence, RI 02906 USA. EM audrey_tyrka@brown.edu RI Tyrka, Audrey/L-2504-2014 FU NIMH NIH HHS [K23 MH067947, R01 MH068767, 1 K23 MH067947] NR 50 TC 33 Z9 34 U1 5 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD MAY PY 2007 VL 115 IS 5 BP 395 EP 402 DI 10.1111/j.1600-0447.2006.00941.x PG 8 WC Psychiatry SC Psychiatry GA 152VM UT WOS:000245390100009 PM 17430418 ER PT J AU Young, RH AF Young, Robert H. TI From Krukenberg to today: The ever present problems posed by metastatic tumors in the ovary. Part II SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review ID ROUND-CELL TUMOR; DIFFERENTIAL-DIAGNOSIS; MALIGNANT-MELANOMA; MORPHOLOGIC SPECTRUM; IMMUNOHISTOCHEMICAL ANALYSIS; HEPATOCELLULAR-CARCINOMA; MUCINOUS TUMORS; BREAST-CANCER; GENITAL-TRACT; ADENOCARCINOMAS AB This is the second of a two-part consideration of metastatic tumors to the ovary. Here, the matter is considered in 16 categories, largely site-specific. The first tumor discussed is gastric carcinoma of intestinal-type whose ovarian manifestations have been the subject of a recent paper which emphasized its differences from the Krukenberg tumor. Coverage of intestinal adenocarcinoma emphasizes the landmark 1987 paper of RH Lash and WR Hart. The section on pancreatic neoplasms reemphasizes the problems caused by metastatic ductal carcinoma, considered primarily in Part 1, and discusses less common issues such as spread of neuroendocrine and acinar cell carcinomas. The limited information on spread of tumors of the gallbladder and extrahepatic bile ducts is then reviewed before more detailed consideration of hepatic neoplasms, prompted by recent contributions on hepatocellular carcinoma and intrahepatic cholangiocarcinoma, the latter based on significant experience with this problem in Thailand. The section on appendiceal neoplasms highlights ovarian spread of diverse tumors ranging from typical intestinal-type adenocarcinoma to signet-ring cell carcinomas with various patterns which in the ovary may prompt diagnoses such as a goblet cell (mucinous) carcinoid tumor, but whose ovarian features place them in the category of a Krukenberg tumor. The diverse problems in differential diagnosis of carcinoid tumor (provoked by nested, acinar, and other patterns, including folliclelike spaces) are then reviewed. The section on breast cancer emphasizes that, although usually a manifestation of late stage disease and often not bulky in the ovaries, metastatic breast cancer may form large masses which can represent the clinical presentation. That patients with breast cancer have an increased risk of primary ovarian cancer and that the latter is more common than secondary spread of breast cancer is noted. The section on lung tumors largely reflects information in a recent paper that small cell carcinoma and adenocarcinoma are the lung cancers that spread to the ovary most commonly. The extremely broad differential diagnosis posed by metastatic malignant melanoma ranging from that of an oxyphilic tumor, to a small cell tumor, to a follicle-forming neoplasm, is then considered. The sections on renal cell carcinoma and other urinary tract neoplasms emphasize the differential diagnosis of metastatic clear cell carcinoma and primary clear cell carcinoma, an issue usually resolvable by an awareness of the various features of the ovarian variant, rarely or never seen in the renal variant. The section on metastatic sarcomas discusses endometrial stromal sarcomas, gastrointestinal stromal neoplasms, and miscellaneous other sarcomas. The endometrial stromal tumors are problematic largely because the history of a primary tumor may be remote, in the ovaries the typical growth and vascular pattern of endometrial stromal neoplasms is not always conspicuous, and some endometrial stromal sarcomas in the ovary show sex cordlike patterns of growth. Recent information has indicated that gastrointestinal stromal tumors may rarely have significant ovarian manifestations and if the primary neoplasm is overlooked, the ovarian tumor may be misdiagnosed, usually as an ovarian fibromatous tumor, but potentially as another primary neoplasm. The sections on ovarian spread of uterine carcinomas emphasize the problems owing to cervical adenocarcinomas, which have a greater tendency to involve the ovaries than squamous cell carcinomas and can simulate primary mucinous or endometioid cancers. The final neoplasms considered are malignant mesothelioma and the desmoplastic small round cell tumor. The microscopic features of malignant mesothelioma are so different from those of primary ovarian carcinoma in most instances that the diagnosis should be readily established on routine microscopic evaluation. The differential diagnosis of the desmoplastic small round cell tumor is more complex because of the greater overlap with the many other small cell malignant tumors that may involve the ovaries primarily or secondarily. Nonetheless, differences exist in most cases and awareness of the entity should lead to consideration of the desmoplastic neoplasm, particularly in a young female. In this area, as in a number of others considered in the review, immunohistochemistry may play a significant, sometimes crucial, role. However, as pointed out in brief concluding remarks, despite the aid of that modality, as in surgical pathology overall, careful consideration of the clinical background, distribution of disease, gross characteristics and spectrum of routine microscopic findings, will lead to the correct diagnosis in the majority of cases and at the very least lead to formulation of a considered differential diagnosis such that use of special techniques may be judicious and those results placed in context of the time-honored clinical and pathologic features. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02115 USA. RP Young, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02115 USA. EM rhyoung@partners.org NR 67 TC 62 Z9 65 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD MAY PY 2007 VL 14 IS 3 BP 149 EP 177 DI 10.1097/PAP.0b013e3180504abf PG 29 WC Pathology SC Pathology GA 165DS UT WOS:000246284700001 PM 17452813 ER PT J AU Martin, EK Taft, CT Resick, PA AF Martin, Elaine K. Taft, Casey T. Resick, Patricia A. TI A review of marital rape SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Review DE domestic violence ID INTIMATE PARTNER VIOLENCE; SEXUAL ASSAULT; BATTERED WOMEN; AGGRESSION; MARRIAGE; VICTIMS; ABUSE; RISK; VICTIMIZATION; CONSEQUENCES AB The current paper represents a comprehensive review of marital rape, including its legal history and numerous aspects of its perpetration and victimization. Specifically, this review focuses on theories and forms of marital rape, the scope of the problem, risk factors, resistance strategies, and marital rape's psychological and physical effects, and help-seeking behaviors and interventions for victims. Historically, marital rape has not been recognized as a criminal act; only recently has marital rape become illegal in all 50 states. Marital rape is a serious societal issue that is experienced by 10% to 14% of all married women and 40% to 50% of battered women. Marriages in which marital rape occurs have significantly higher rates of non-sexual violence and marital dissatisfaction, as well as lower ratings of marital quality. Victims who resist marital rape often employ verbal means of resistance. However, most of marital rape victims are either unable or afraid to resist sexual aggression by their husbands. Victims of marital rape experience significant levels of posttraumatic stress disorder (PTSD), depression, gynecological problems, and negative physical health symptoms. Victims of marital rape seek help from a variety of different resources. Seeking help from social service agencies and the law appears to be the most effective behaviors for ending marital rape. Stress inoculation therapy and cognitive processing therapy are promising treatments for victims of marital rape. The literature on marital rape is characterized by considerable methodological problems, and further research is needed to gain a better understanding of this problem. Published by Elsevier Ltd. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Resick, PA (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM patricia.resick@va.gov NR 74 TC 51 Z9 52 U1 8 U2 40 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-1789 J9 AGGRESS VIOLENT BEH JI Aggress. Violent Behav. PD MAY-JUN PY 2007 VL 12 IS 3 BP 329 EP 347 DI 10.1016/j.avb.2006.10.003 PG 19 WC Criminology & Penology; Psychology, Multidisciplinary SC Criminology & Penology; Psychology GA 155LU UT WOS:000245579700005 ER PT J AU Graham, J Bennett, IM Holmes, WC Gross, R AF Graham, Joseph Bennett, Ian M. Holmes, William C. Gross, Robert TI Medication beliefs as mediators of the health literacy-antiretroviral adherence relationship in HIV-infected individuals SO AIDS AND BEHAVIOR LA English DT Article DE HIV-1; antiretroviral therapy; adherence; health literacy ID VIRAL LOAD; THERAPY; KNOWLEDGE; CARE; ASSOCIATION; PATTERNS; OUTCOMES; ADULTS; SKILLS; AIDS AB Identifying modifiable barriers to antiretroviral adherence remains an important aim. We hypothesized that mistaken beliefs regarding taking HIV medications mediated the relation between low literacy and poor adherence. We studied 87 HIV-infected individuals on standard antiretroviral regimens for >= 3 months. Adherence was assessed using pharmacy refill records. Medication beliefs, including an individual's norm for acceptable adherence, were measured using questions developed by expert panel. Literacy was associated with < 95% adherence (64% for < 9th grade level vs. 40% for < 9th grade level). Participants with < 95% adherence had a lower threshold of acceptable adherence than those with >= 95% adherence [80% adherence (interquartile range 70-90%) vs. 90% adherence (interquartile range 80-90%)]. However, the effect was independent of literacy. No other beliefs assessed were associated with adherence. Although the beliefs assessed do not mediate the relation between literacy and adherence, we identified low adherence norms as a potentially modifiable belief associated with adherence. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Family Med & Community Hlth, Philadelphia, PA 19104 USA. RP Gross, R (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 804 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rgross@cceb.med.upenn.edu OI Bennett, Ian/0000-0002-7139-9456 FU AHRQ HHS [HS10399]; NIAID NIH HHS [U01-AI32783, P30-AI45008]; NICHD NIH HHS [K23 HD048915, K23 HD048915-03]; NIMH NIH HHS [MH-01854] NR 28 TC 31 Z9 32 U1 1 U2 6 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 MAY PY 2007 VL 11 IS 3 BP 385 EP 392 DI 10.1007/s10461-006-9164-9 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 153TP UT WOS:000245458400004 PM 17053858 ER PT J AU Durazzo, TC Gazdzinski, S Meyerhoff, DJ AF Durazzo, Timothy C. Gazdzinski, Stefan Meyerhoff, Dieter J. TI The neurobiological and neurocognitive consequences of chronic cigarette smoking in alcohol use disorders SO ALCOHOL AND ALCOHOLISM LA English DT Review ID CEREBRAL-BLOOD-FLOW; ALZHEIMERS-DISEASE; NEUROPSYCHIATRIC DISORDERS; BRAIN ATROPHY; COGNITIVE PERFORMANCE; ABSTINENT ALCOHOLICS; POSTURAL STABILITY; COCAINE DEPENDENCE; GLUCOSE-METABOLISM; MAJOR DEPRESSION AB A vast body of research attests to the adverse effects of chronic smoking on cardiac, pulmonary, and vascular function as well as the increased risk for various forms of cancer. However, comparatively little is known about the effects of chronic smoking on human brain function. Although smoking rates have decreased in the developed world, they remain high in individuals with alcohol use disorders. Despite the high prevalence of comorbid chronic smoking in alcohol use disorders, very few studies have addressed the potential neurobiological or neurocognitive effects of chronic smoking in alcohol use disorders. Here, we briefly review the existing literature on the neurobiological and neurocognitive consequences of chronic cigarette smoking and summarize our neuroimaging and neurocognitive studies on the effects of comorbid chronic excessive alcohol consumption and cigarette smoking in treatment-seeking and treatment-naive populations. Our research suggests comorbid chronic cigarette smoking modulates magnetic resonance-detectable brain injury and neurocognition in alcohol use disorders and that neurobiological recovery in our abstinent alcoholics is adversely affected by chronic smoking. Consideration of the potential separate effects and interactions of chronic smoking and alcohol consumption may foster a better understanding of specific mechanisms and neurocognitive consequences of brain injury in alcoholism and of brain recovery during sustained abstinence from alcohol. The material presented also contributes to ongoing discussions about treatment strategies for comorbid alcoholism and cigarette smoking and will hopefully stimulate further research into the neurobiological and neurocognitive consequences of chronic smoking in alcoholism and other substance use disorders. C1 Dept Vet Affairs Med Ctr, Ctr Neuroimaging Neurodegenerat Dis, San Francisco, CA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, 114M,4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU NIAAA NIH HHS [P01 AA11493, R01 AA10788] NR 107 TC 55 Z9 58 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD MAY-JUN PY 2007 VL 42 IS 3 BP 174 EP 185 DI 10.1093/alcalc/agm020 PG 12 WC Substance Abuse SC Substance Abuse GA 185QN UT WOS:000247725600003 PM 17526627 ER PT J AU Park, ER Storfer-Isser, A Kelleher, KJ Stein, REK Heneghan, AM Chaudron, L Hoagwood, KE O'Connor, KG Horwitz, SM AF Park, Elyse R. Storfer-Isser, Amy Kelleher, Kelly J. Stein, Ruth E. K. Heneghan, Amy M. Chaudron, Linda Hoagwood, Kimberly Eaton O'Connor, Karen G. McCue Horwitz, Sarah TI In the moment: Attitudinal measure of pediatrician management of maternal depression SO AMBULATORY PEDIATRICS LA English DT Article DE attitudes; maternal depression; survey ID WELL-CHILD VISITS; RESPONSE RATES; PERCEIVED RESPONSIBILITIES; POSTPARTUM DEPRESSION; PHYSICIANS; CARE; IDENTIFICATION; SYMPTOMS; MOTHERS; PREVENTION AB Objective. - Pediatricians are in a good position to identify women who struggle with depression, but studies show low rates of pediatrician identification and management. It is likely that pediatricians' management of maternal depression may vary on the basis of their attitudes, but no instrument has been developed to measure these attitudes. We sought to develop a measure of pediatricians' attitudes about managing maternal depression and to identify characteristics associated with pediatricians' attitudes about managing maternal depression. Methods. - We conducted a cross-sectional analysis of data provided by 651 practicing, nontrainee pediatricians (response rate 57.5%) surveyed through an American Academy of Pediatrics 2004 Periodic Survey. An exploratory principal components analysis was used to investigate the interrelationships among the attitudinal items. Multivariable linear regression was used to assess the adjusted associations between physician and practice characteristics and attitudes. Results. - The attitudinal measure consisted of 3 subscales: acknowledging maternal depression, perceptions of mothers' beliefs, and treating maternal depression. Clinical approaches (eg, interest in further education on identifying or treating maternal depression) and training and work characteristics were significantly related to pediatricians' attitudes; patient characteristics (eg, type of insurance and ethnicity/race) were not significantly associated with pediatricians' attitudes. Conclusions. - We developed a measure to assess pediatricians' attitudes about managing maternal depression. The findings from this study can be used to develop and assess interventions that improve pediatricians' attitudes about acknowledging maternal depression, perceptions of mothers' beliefs, and treating maternal depression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Inst Hlth Policy, Boston, MA 02114 USA. Case Western Reserve, Dept Epidemiol, Cleveland, OH USA. Case Western Reserve, Dept Biostat, Cleveland, OH USA. Case Western Reserve, Dept Pediat, Cleveland, OH USA. Case Western Reserve, Sch Med, Cleveland, OH USA. Ohio State Univ, Dept Pediat, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Albert Einstein Coll Med, Montefiore Med Ctr, Dept Pediat, New York, NY USA. Univ Rochester, Dept Psychiat, Rochester, NY 14627 USA. Univ Rochester, Dept Pediat, Rochester, NY 14627 USA. Univ Rochester, Dept Obstet & Gynecol, Rochester, NY 14627 USA. Columbia Univ, Dept Psychiat, New York, NY 10027 USA. Amer Acad Pediat, Res Dept, Elk Grove Village, IL USA. RP Park, ER (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Inst Hlth Policy, 50 Stanford Sr,9th Floor, Boston, MA 02114 USA. EM epark@partners.org RI Kelleher, Kelly/E-3361-2011 NR 31 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD MAY-JUN PY 2007 VL 7 IS 3 BP 239 EP 246 DI 10.1016/j.ambp.2007.03.002 PG 8 WC Pediatrics SC Pediatrics GA 171OR UT WOS:000246745800008 PM 17512885 ER PT J AU Jha, AK Staiger, DO Lucas, FL Chandra, A AF Jha, Ashish K. Staiger, Douglas O. Lucas, F. Lee Chandra, Amitabh TI Do race-specific models explain disparities in treatments after acute myocardial infarction? SO AMERICAN HEART JOURNAL LA English DT Article ID COOPERATIVE CARDIOVASCULAR PROJECT; INSTITUTE-OF-MEDICINE; RACIAL-DIFFERENCES; CARE; SEX AB Background Racial differences in healthcare are well known, although some have challenged previous research where risk-adjustment assumed covariates affect whites and blacks equally. if incorrect, this assumption may misestimate disparities. We sought to determine whether clinical factors affect treatment decisions for blacks and whites equally. Methods We used data from the Cardiovascular Cooperative Project for 130709 white and 8286 black patients admitted with an acute myocardial infarction. We examined the rates of receipt of 6 treatments using conventional common-effects models, where covariates affect whites and blacks equally, and race-specific models, where the effect of each covariate can vary by race. Results The common-effects models showed that blacks were less likely to receive 5 of the 6 treatments (odds ratios 0.64-1.10). The race-specific models displayed nearly identical treatment disparities (odds ratios 0.65-1.07). We found no interaction effect, which systematically suggested the presence of race-specific effects. Conclusions Race-specific models yield nearly identical estimates of racial disparities to those obtained from conventional models. This suggests that clinical variables, such as hypertension or diabetes, seem to affect treatment decisions equally for whites and blacks. Previously described racial disparities in care are unlikely to be an artifact of misspecified models. C1 Harvard Univ, Dept Hlth Policy & Management, Boston, MA 02115 USA. Va Boston Healthcare Syst, Boston, MA USA. Harvard Univ, John F Kennedy, Sch Govt, Cambridge, MA 02138 USA. Dartmouth Coll Sch Med, Hanover, NH USA. Dartmouth Coll, Dept Econ, Hanover, NH 03755 USA. Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME USA. RP Jha, AK (reprint author), Harvard Univ, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu FU NIA NIH HHS [P01 AG019783-06, P01 AG19783-02, P01 AG019783] NR 16 TC 16 Z9 16 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2007 VL 153 IS 5 BP 785 EP 791 DI 10.1016/j.ahj.2007.02.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 167SX UT WOS:000246472800011 PM 17452154 ER PT J AU Steinberg, BA Steg, PG Bhatt, DL Fonarow, GC Zeymer, U Cannon, CP AF Steinberg, Benjamin A. Steg, P. Gabriel Bhatt, Deepak L. Fonarow, Gregg C. Zeymer, Uwe Cannon, Christopher P. CA REACH Registry Investigators TI Comparisons of guideline-recommended therapies in patients with documented coronary artery disease having percutaneous coronary intervention versus coronary artery bypass grafting versus medical therapy only (from the REACH International Registry) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ELEVATION MYOCARDIAL-INFARCTION; HEART-ASSOCIATION; UPDATE; WOMEN AB To evaluate current compliance with recommendations for medical therapy in patients with coronary artery disease (CAD), the relation between previous revascularization and use of guideline-recommended therapies was investigated. From 5,400 outpatient practices in 44 countries, we compared baseline characteristics and medical therapy of 40,450 patients with documented CAD (all with previous myocardial infarction, percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], or angina pectoris) by previous revascularization status. Approximately 33% of patients had previous CABG, 33% had previous PCI, and 33% had no previous revascularization. Patients with previous CABG were older and often men and diabetic. Patients with previous PCI were the youngest. Guideline-recommended medical therapy use was significantly higher in those with previous revascularization. Antiplatelet therapy in medically managed patients was 80% versus 86%. and 91% for those with previous CABG or PCI, respectively. Use of any lipid-lowering agent in those with previous CABG or PCI was 86% in the 2 groups versus 70% in patients who were medically managed. Angiotensin-converting enzyme inhibitors and angiotensin receptor, blockers were used in similar ratios among groups. Previous revascularization appears to be associated with better use of guideline-recommended medical treatment. These trends were similar for patients from the United States versus everywhere else. In conclusion, use of evidence-based, guideline-recommended therapies in outpatients with CAD needs to improve, especially in medically managed patients. (C) 2007 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Hop Bichat Claude Bernard, Serv Cardiol, F-75877 Paris, France. Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Herzzentrum Ludwigshafen, Med Klin 2, Ludwigshafen, Germany. RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 13 TC 24 Z9 29 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2007 VL 99 IS 9 BP 1212 EP 1215 DI 10.1016/j.amjcard.2006.12.039 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 163OE UT WOS:000246168600008 PM 17478144 ER PT J AU Stein, PD Beemath, A Quinn, DA Olson, RE Goodman, LR Gottschalk, A Hales, CA Hull, RD Leeper, KV Sostman, D Weg, JG Woodard, PK AF Stein, Paul D. Beemath, Afzal Quinn, Deborah A. Olson, Ronald E. Goodman, Lawrence R. Gottschalk, Alexander Hales, Charles A. Hull, Russell D. Leeper, Kenneth V., Jr. Sostman, Dirk Weg, John G. Woodard, Pamela K. TI Usefulness of multidetector spiral computed tomography according to age and gender for diagnosis of acute pulmonary embolism SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB Data from the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) were evaluated to test the hypothesis that the performance of multidetector computed tomographic (CT) pulmonary angiography and CT venography is independent of a patient's age and gender. In 773 patients with adequate CT pulmonary angiography and 737 patients with adequate CT pulmonary angiography and CT venography, the sensitivity and specificity for pulmonary embolism for groups of patients aged 18 to 59, 60 to 79, and 80 to 99 years did not differ to a statistically significant extent, nor were there significant differences according to gender. Overall, however, the specificity of CT pulmonary angiography was somewhat greater in women, but in men and women, it was >= 93%. In conclusion, the results indicate that multidetector CT pulmonary angiography and CT pulmonary angiography and CT venography may be used with various diagnostic strategies in adults of all ages and both genders. (C) 2007 Elsevier Inc. All rights reserved. C1 St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI USA. Wayne State Univ, Dept Med, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Oakland Univ, Dept Grants & Contracts, Rochester, MI USA. Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. Michigan State Univ, Dept Radiol, E Lansing, MI 48824 USA. Univ Calgary, Dept Med, Calgary, AB T2N 1N4, Canada. Emory Univ, Dept Med, Atlanta, GA 30322 USA. Cornell Univ, Weill Med Coll, Off Dean, Houston, TX USA. Methodist Hosp, Houston, TX 77030 USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Washington Univ, Dept Radiol, St Louis, MO USA. RP Stein, PD (reprint author), St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI USA. EM steinp@trinity-health.org FU NHLBI NIH HHS [HL67453, HL63928, HL63899, HL63982, HL63940, HL63981, HL63931] NR 5 TC 11 Z9 11 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 2007 VL 99 IS 9 BP 1303 EP 1305 DI 10.1016/j.amjcard.2006.12.051 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 163OE UT WOS:000246168600026 PM 17478162 ER PT J AU Salem, RO Van Cott, EM AF Salem, Raneem O. Van Cott, Elizabeth M. TI A new automated screening assay for the diagnosis of von Willebrand disease SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article AB A new, automated assay for von Willebrand factor (vWF) activity has recently become commercially available (HemosIL vWF activity assay, Instrumentation Laboratories, Lexington, MA). We prospectively studied 61 specimens from 58 patients undergoing laboratory testing for suspicion of von Willebrand disease with this new method, in comparison with the established ristocetin cofactor method. Assays for factor VIII and vWF antigen were also performed using an established method on an MDA-180 coagulation analyzer (bioMerieux, Durham, NC) and a new method on an ACL TOP coagulation analyzer (Instrumentation Laboratories). Blood types were determined. The results showed no significant difference between the assays for factor VIII (mean, 97% for MDA-180 and ACL TOP; P =.494) or vWF antigen (mean, MDA-180,109%; ACL TOP, 111%; P=766). The mean result for the ristocetin cofactor assay was 106% vs 93% with the automated vWF activity (P =.007). The automated activity assay was 100% sensitive and 86% specific for detecting vWF abnormalities and seems to be a suitable screening test. Abnormal results should be followed up with a ristocetin cofactor activity assay for confirmation. Further study is recommended to confirm these conclusions. C1 Massachusetts Gen Hosp, Clin Labs, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Clin Labs, Div Lab Med, Dept Pathol, Gray 235,55 Fruit St, Boston, MA 02114 USA. NR 8 TC 20 Z9 21 U1 1 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 2007 VL 127 IS 5 BP 730 EP 735 DI 10.1309/CEPND3LFHQ87XU4D PG 6 WC Pathology SC Pathology GA 159OH UT WOS:000245875100006 PM 17439831 ER PT J AU Chen, HL O'Reilly, E McCullough, ML Rodriguez, C Schwarzschild, MA Calle, EE Thun, MJ Ascherio, A AF Chen, Honglei O'Reilly, Ellis McCullough, Marjorie L. Rodriguez, Carmen Schwarzschild, Michael A. Calle, Eugenia E. Thun, Michael J. Ascherio, Alberto TI Consumption of dairy products and risk of Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE dairy products; diet; milk; Parkinson disease ID FOOD-FREQUENCY QUESTIONNAIRE; SOCIETY CANCER PREVENTION; URIC-ACID LEVELS; ENDOGENOUS AMINE; DIETARY FACTORS; COHORT; BRAIN; MEN; 1-BENZYL-1,2,3,4-TETRAHYDROISOQUINOLINE; TETRAHYDROISOQUINOLINE AB The authors prospectively investigated the association between intake of dairy products and risk of Parkinson's disease among 57,689 men and 73,175 women from the American Cancer Society's Cancer Prevention Study 11 Nutrition Cohort. A total of 250 men and 138 women with Parkinson's disease were identified during follow-up (1992-2001). Dairy product consumption was positively associated with risk of Parkinson's disease: Compared with the lowest intake quintile, the corresponding relative risks for quintiles 2-5 were 1.4, 1.4, 1.4, and 1.6 (95 percent confidence interval (CI): 1.1, 2.2; p for trend = 0.05). A higher risk among dairy product consumers was found in both men and women, although the association in women appeared nonlinear. Meta-analysis of all prospective studies confirmed a moderately elevated risk of Parkinson's disease among persons with high dairy product consumption: For extreme intake categories, relative risks were 1.6 (95 percent CI: 1.3, 2.0) for both sexes, 1.8 for men (95 percent CI: 1.4, 2.4), and 1.3 for women (95 percent CI: 0.8, 2.1). These data suggest that dairy consumption may increase the risk of Parkinson's disease, particularly in men. More studies are needed to further examine these findings and to explore underlying mechanisms. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Amer Canc Soc, Epidemiol & Surveillance Res dept, Atlanta, GA 30329 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2,Room 335, Boston, MA 02115 USA. EM aascheri@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NINDS NIH HHS [K08 NS048468, NS48468] NR 29 TC 59 Z9 61 U1 2 U2 9 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 MAY 1 PY 2007 VL 165 IS 9 BP 998 EP 1006 DI 10.1093/aje/kwk089 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 159VY UT WOS:000245896900004 PM 17272289 ER PT J AU Shaib, YH El-Serag, HB Nooka, AK Thomas, M Brown, TD Patt, YZ Hassan, MM AF Shaib, Yasser H. El-Serag, Hashem B. Nooka, Ajay K. Thomas, Melanie Brown, Thomas D. Patt, Yehuda Z. Hassan, Manal M. TI Risk factors for intrahepatic and extrahepatic cholangiocarcinoma: A hospital-based case-control study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HEPATITIS-C VIRUS; POLYMERASE CHAIN-REACTION; UNITED-STATES; RNA SEQUENCES; B SURFACE; LIVER; CANCER; EPIDEMIOLOGY; INFECTION; CARCINOMA AB BACKGROUND: The risk factors for cholangiocarcinoma are poorly defined in the United States. We evaluated hepatitis C virus (HCV), hepatitis B virus (HBV), and liver cirrhosis as risk factors for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). METHODS: A case-control study in which cases were cholangiocarcinoma patients referred to the M.D. Anderson Cancer Center between 1992 and 2002 and controls were healthy individuals. Information about liver diseases, family history, diabetes, smoking, and alcohol consumption were collected on both groups. Blood from all participants was tested for HBV and HCV markers. RESULTS: We identified 246 cases (83 ICC and 163 ECC) and matched them to 236 controls. Compared with controls, ICC patients had a higher prevalence of anti-HCV antibodies (6.0% vs 0.8%, P = 0.01), anti-HBc (9.6% vs 0%, P < 0.0001), and heavy alcohol consumption (21.7% vs 3.8%, P < 0.0001). The adjusted odds ratio and 95% confidence interval (CI) were 7.9 (95% CI 1.3-84.5), 28.6 (95% CI 3.9-1,268.1), and 5.9 (95% CI 2.1-17.4), respectively. Only heavy alcohol consumption was higher in patients with ECC than in controls (17.8% vs 3.8%, P = 0.003). The prevalence of diabetes and smoking were not significantly different between cases (ICC or ECC) and controls. The prevalence of cirrhosis was higher in patients with ICC than those with ECC (24.1% vs 4.9%, P < 0.0001). CONCLUSIONS: Liver cirrhosis and chronic HCV infection are possible risk factors for ICC but not ECC. Heavy alcohol consumption is a risk factor for both ICC and ECC. C1 MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ New Mexico, Ctr Canc, Sect Gastrintestinal Oncol, Albuquerque, NM 87131 USA. RP Hassan, MM (reprint author), MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 16 TC 130 Z9 139 U1 2 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2007 VL 102 IS 5 BP 1016 EP 1021 DI 10.1111/j.1572-0241.2007.01104.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 163TS UT WOS:000246186700017 PM 17324130 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Time trends of ulcer mortality in non-European countries SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID PEPTIC-ULCER; DISEASE; EPIDEMIOLOGY; RATES; PATTERNS AB AIMS: The aim of the present study was to follow the time trends of mortality from gastric and duodenal ulcer in countries outside Europe and compare them with previous reports of ulcer mortality from Europe and North America. METHODS: Mortality data from eight different countries were analyzed, including Argentina, Australia, Chile, Hong Kong, Japan, Mexico, Singapore, and Taiwan. The age-standardized death rates of individual countries were followed from 1971 to 2004. Japan and Australia had mortality data for more than 50 yr that provided the opportunity to conduct a birth-cohort analysis. RESULTS: The data from all countries were characterized by a decline in gastric and duodenal ulcer mortality. Except for Hong Kong, mortality from gastric ulcer was higher than mortality from duodenal ulcer. In Japan and Australia, mortality from gastric and duodenal ulcer displayed time trends that were consistent with an underlying birth-cohort phenomenon. The risk of dying from gastric and duodenal ulcer increased in consecutive generations born between the mid- and the end of the nineteenth century and decreased in all subsequent generations. The peak mortality from gastric ulcer occurred among generations born in 1875, whereas peak mortality from duodenal ulcer occurred among generations born 10-20 yr later. CONCLUSIONS: The ubiquitous decline in ulcer mortality in countries from different parts of the world is likely to be associated with a worldwide decline in the occurrence of H. pylori infection. The events accompanying the receding infection in developed countries must have similarly affected populations exposed to increasing standards of hygiene. C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Portland, OR USA. NR 19 TC 21 Z9 22 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2007 VL 102 IS 5 BP 1101 EP 1107 DI 10.1111/j.1572-0241.2007.01157.x PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 163TS UT WOS:000246186700029 PM 17355419 ER PT J AU Rosendoff, C Beeri, MS Silverman, JM AF Rosendoff, Clive Beeri, Michal S. Silverman, Jeremy M. TI Cardiovascular risk factors for Alzheimer's disease SO AMERICAN JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Review ID ADVANCED GLYCATION ENDPRODUCTS; ELDERLY JAPANESE POPULATION; TOTAL CHOLESTEROL LEVELS; SYSTOLIC BLOOD-PRESSURE; AMYLOID-BETA PEPTIDE; E EPSILON-4 ALLELE; COGNITIVE FUNCTION; APOLIPOPROTEIN-E; TOTAL HOMOCYSTEINE; DIABETES-MELLITUS AB There is now sizable literature on the association between traditional cardiovascular risk factors and Alzheimer's disease (AD). Based on epidemiologic studies, both cross-sectional and' longitudinal, there are statistically significant correlations between the prevalence of AD and diabetes, hypercholesterolemia, hypertension, hyperhomocysteinemia, dietary saturated fats, cholesterol, antioxidants, alcohol consumption, smoking, physical activity, the presence of atrial fibrillation, atherosclerotic disease, and the plasma concentration of some hemostatic factors. Most of the cardiovascular risk factors found to be associated with AD are age-dependent, and the prevalence of AD increases with age. Therefore, the association could simply be attributed to aging. On the other hand, the common pathogenetic mechanisms for the generation of both atherosclerotic disease and AD, such as inflammation and the generation of free radicals, suggest a causal link. If this is the case, the identification of modifiable risk factors for dementia becomes a research priority,and early intervention aimed at reducing those cardiovascular risk factors a therapeutic imperative. C1 James J Peters VA Med Ctr, Dept Med 111, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Rosendoff, C (reprint author), James J Peters VA Med Ctr, Dept Med 111, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM clive.rosendorff@va.gov NR 86 TC 77 Z9 82 U1 1 U2 7 PU LE JACQ LTD PI DARIEN PA 3 PARKLANDS DRIVE, DARIEN, CT 06820 USA SN 1076-7460 J9 AM J GERIATR CARDIOL JI Am. J. Geriatr. Cardiol. PD MAY-JUN PY 2007 VL 16 IS 3 BP 143 EP 149 DI 10.1111/j.1076-7460.2007.06696.x PG 7 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA 164LN UT WOS:000246235300003 PM 17483665 ER PT J AU Chodosh, J Kado, DM Seeman, TE Karlamangla, AS AF Chodosh, Joshua Kado, Deborah M. Seeman, Teresa E. Karlamangla, Arun S. TI Depressive symptoms as a predictor of cognitive decline: MacArthur studies of successful aging SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depression; dementia; distress; cognitive decline ID MENTAL STATUS QUESTIONNAIRE; ALZHEIMERS-DISEASE; OLDER PERSONS; INFLAMMATORY MARKERS; RISK-FACTOR; FOLLOW-UP; COMMUNITY; DEMENTIA; IMPAIRMENT; ASSOCIATION AB Objective: The prevalence of dementia continues to rise, and yet, there are few known modifiable risk factors. Depression, as a treatable condition, may be important in the development of dementia. Our objective was to examine the association between depressive symptoms and longitudinal cognitive changes in older adults who were high-functioning at baseline. Methods: The authors analyzed data from a community-based cohort (aged 70-79 at baseline), who, at study entry, scored 7 or more (out of 9) on the Short Portable Mental Status Questionnaire (SPMSQ). Depressive symptoms were assessed at baseline using the depression subscale of the Hopkins Symptom Check List. Cognitive performance was measured at baseline and at seven-year follow up by the SPMSQ and by summary scores from standard tests of naming, construction, spatial recognition, abstraction, and delayed recall. Results: After adjusting for potential confounders, including age, education, and chronic health conditions such as diabetes, heart attack, stroke, and hypertension, a higher number of baseline depressive symptoms were strongly associated with greater seven-year decline in cognitive performance and with higher odds of incident cognitive impairment, i.e., decline in SPMSQ score to <= 6 (adjusted odds ratio per quartile of depressive symptoms score: 1.34, 95% confidence interval: 1.10-1.68). Conclusions: Depressive symptomatology independently predicts cognitive decline and incident cognitive impairment in previously high-functioning older persons. C1 VA Greater Los Angeles Hlth Syst, HSR&D COE, Los Angeles, CA 90073 USA. VA Greater Los Angeles Hlth Syst, GRECC, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90024 USA. RP Chodosh, J (reprint author), VA Greater Los Angeles Hlth Syst, HSR&D COE, 11G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jchodosh@mednet.ucla.edu OI Chodosh, Joshua/0000-0001-7784-4306 FU NIA NIH HHS [1K12AG01004, AG-17056, AG-17265] NR 51 TC 67 Z9 68 U1 4 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAY PY 2007 VL 15 IS 5 BP 406 EP 415 DI 10.1097/01.JGP.0b013e31802c0c63 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 165IZ UT WOS:000246299600006 PM 17353297 ER PT J AU Bartel, SB AF Bartel, Sylvia B. TI Safe practices and financial considerations in using oral chemotherapeutic agents SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE antineoplastic agents; caregivers; charity; costs; dispensing; dosage schedules; drug administration; drug administration routes; economics; errors, medication; health-benefit programs; industry, pharmaceutical; neoplasms; patient information; patients; prescribing; reimbursement; safety; toxicity; toxicity, environmental ID PRESCRIPTION DRUG IMPROVEMENT; MODERNIZATION ACT AB Purpose. Safe handling practices and financial concerns associated with oral chemotherapy in non-traditional settings are discussed. Summary. Oral chemotherapy may pose a risk to patients because of a narrow therapeutic index, complex dosing regimen, dispensing by community pharmacists without prescription order review by an oncology pharmacist or nurse, or self-administration in the home or another nontraditional setting, where patient monitoring is infrequent. Errors in prescribing, dispensing, and administration and patient or caregiver misunderstandings are potential problems with the use of oral chemotherapy that need to be addressed when developing safe practices. Changes in Medicare pharmaceutical reimbursement rates and rules need to be monitored because they have the potential to affect patient care and outcomes. Patient assistance programs and advocacy groups can help alleviate financial concerns associated with oral chemotherapy. Conclusion. Consensus guidelines specific to safe handling of oral chemotherapy in the home or other nontraditional setting need to be developed. Also, healthcare providers must understand reimbursement and provide direction to patients when patient assistance programs or advocacy groups can assist with the financial challenges of oral chemotherapy. C1 Dana Farber Canc Inst, Dept Pharm, Boston, MA 02115 USA. RP Bartel, SB (reprint author), Dana Farber Canc Inst, Dept Pharm, 44 Binney St,Dana Bldg,Room DL294, Boston, MA 02115 USA. EM sylvia_bartel@dfci.harvard.edu NR 20 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 1 PY 2007 VL 64 SU S BP S8 EP S14 DI 10.2146/ajhp070036 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 165YB UT WOS:000246342600003 PM 17468158 ER PT J AU Goodin, S Aisner, J Bartel, SB Viele, CS AF Goodin, Susan Aisner, Joseph Bartel, Sylvia B. Viele, Carol S. TI Current issues associated with oral chemotherapy: A roundtable discussion SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material C1 Canc Inst New Jersey, Div Pharmaceut Sci, New Brunswick, NJ 08901 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ 08901 USA. Dana Farber Canc Inst, Dept Pharm, Boston, MA 02115 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94044 USA. RP Goodin, S (reprint author), Canc Inst New Jersey, Div Pharmaceut Sci, 195 Little Albany St, New Brunswick, NJ 08901 USA. EM goodin@umdnj.edu; desouzbe@umdnj.edu; sylvia_bartel@dfci.harvard.edu; carol.viele@ucsfmedctr.org NR 0 TC 2 Z9 3 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 1 PY 2007 VL 64 SU S BP S33 EP S35 DI 10.2146/ajhp070038 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 165YB UT WOS:000246342600006 PM 17468155 ER PT J AU Palmas, W Pickering, T Eimicke, JP Moran, A Teresi, J Schwartz, JE Field, L Weinstock, RS AF Palmas, Walter Pickering, Thomas Eimicke, Joseph P. Moran, Andrew Teresi, Jeanne Schwartz, Joseph E. Field, Lesley Weinstock, Ruth S. TI Value of ambulatory arterial stiffness index and 24-h pulse pressure to predict progression of albuminuria in elderly people with diabetes mellitus SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE albuminuria; arterial stiffness; pulse pressure; diabetes mellitus; ambulatory blood pressure ID BLOOD-PRESSURE; CARDIOVASCULAR RISK; FOLLOW-UP; EXCRETION; MICROALBUMINURIA; MORTALITY; NIDDM; POPULATION; PREVALENCE; DESIGN AB Background: Ambulatory 24-h pulse pressure predicts progression of albuminuria in people with diabetes mellitus. It is not known whether the ambulatory arterial stiffness index (AASI) may add to that prediction. Methods: We compared the multivariate-adjusted association of AASI and 24-h pulse pressure with progression of urine albumin excretion during follow-up in a multiethnic cohort of older people with type-2 diabetes mellitus. The baseline evaluation included office and 24-h ambulatory blood pressure (BP) measurements, and a spot urine measurement of albumin-to-creatinine ratio (ACR). The ACR measurements were repeated annually during 3 years. Results: The AASI was >= 0.55 units in 47% of those exhibiting progression of albuminuria, and in 37% of those without progression (P = .004), whereas 24-h pulse pressure was >= 65 mm Hg in 50% and 38% of those with and without progression, respectively (P = .001). In repeated measures mixed linear model (n = 1043), after adjustment for several covariates including office pulse pressure, AASI in the fourth quartile was independently associated with higher follow-up ACR (P = .024). However, that association did not persist after adjusting for 24-h pulse pressure, which was an independent predictor (P <.001). Cox proportional hazards models examined progression of albuminuria in 957 participants without macroalbuminuria at baseline. The hazard ratio (95% CI) for AASI >= 0.55 units was 1.37 (1.02-1.83) after multivariable adjustment, including office pulse pressure. But AASI was not an independent predictor after adjustment for ambulatory pulse pressure, which was again an independent predictor (P = .033). Conclusions: Ambulatory 24-h pulse pressure outperformed AASI in predicting progression of albuminuria in elderly people with type 2 diabetes. C1 Columbia Univ, Dept Med, New York, NY 10027 USA. Columbia Univ, Behav Cardiovasc Hlth & Hypertens Program, New York, NY 10027 USA. Hebrew Home Aged, Div Res, Bronx, NY USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. Columbia Univ, Stroud Ctr, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, Fac Med, New York, NY 10032 USA. SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. SUNY Upstate Med Univ, Div Endocrinol Diabet & Metab, Syracuse, NY USA. VA Med Ctr, Dept Vet Affairs, Syracuse, NY USA. Columbia Univ, Joseph Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. Columbia Univ, Dept Biomed Informat, New York, NY 10027 USA. RP Palmas, W (reprint author), Div Gen Med, 622 W 168th St,PH 9-E, New York, NY 10032 USA. EM wp56@columbia.edu NR 32 TC 19 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAY PY 2007 VL 20 IS 5 BP 493 EP 500 DI 10.1016/j.amjhyper.2006.11.005 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 170QJ UT WOS:000246678700006 PM 17485009 ER PT J AU McFarland, LV Beneda, HW Clarridge, JE Raugi, GJ AF McFarland, Lynne V. Beneda, Henry W. Clarridge, Jill E. Raugi, Gregory J. TI Implications of the changing face of Clostridium difficile disease for health care practitioners SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Review ID ANTIBIOTIC-ASSOCIATED DIARRHEA; BINARY-TOXIN GENES; PROTON PUMP INHIBITORS; INFECTION-CONTROL; RISK-FACTORS; NOSOCOMIAL TRANSMISSION; HOSPITALIZED-PATIENTS; ENVIRONMENTAL CONTAMINATION; INTRAVENOUS IMMUNOGLOBULIN; PIPERACILLIN-TAZOBACTAM AB Recent reported outbreaks of Clostridium difficile-associated disease in Canada have changed the profile of C difficile infections. Historically C difficile disease was thought of mainly as a nosocomial disease associated with broad-spectrum antibiotics, and the disease was usually riot life threatening. The ernergence of an epidemic strain, BI/NAPI/027, which produces a binary toxin in addition to the 2 classic C difficile toxins A and B and is resistant to some fluoroquinolones, was associated with large numbers of cases with high rates of mortality Recently, C difficile has been reported more frequently in non hospital-based settings, such as community-acquired cases. The C difficile disease is also being reported in populations once considered of low risk (children and young healthy women). In addition, poor response to metronidazole treatment is increasing, Faced with an increasing incidence of C difficile infections and the changing profile of patients who become infected, this paper will reexamine the current concepts on the epidemiology and treatment of C difficile-associated disease, present new hypotheses for risk factors, examine the role of spores in the transmission of C difficile, and provide recommendations that may enhance infection control practices. C1 VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, Seattle, WA 98101 USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Infect Control, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Lab Serv, Seattle, WA 98101 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Vet Adm Puget Sound Hlth Care Syst, Dermatol Sect, Primary & Specialty Serv, Seattle, WA USA. Univ Washington, Div Dermatol, Dept Med, Seattle, WA 98195 USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, S152,1100 Olive Way 1400, Seattle, WA 98101 USA. EM Lynne.McFarland@va.gov NR 171 TC 64 Z9 65 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAY PY 2007 VL 35 IS 4 BP 237 EP 253 DI 10.1016/j.ajic.2006.06.004 PG 17 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 168BY UT WOS:000246498500006 PM 17482995 ER PT J AU Wyatt, C Konduri, V Eng, J Rohatgi, R AF Wyatt, Christina Konduri, Vinaya Eng, John Rohatgi, Rajeev TI Reporting of estimated GFR in the primary care clinic SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE glomerular filtration rate; chronic kidney disease; angiotensin-converting enzyme inhibitor; angiotensin receptor blocker; blood pressure control ID CHRONIC RENAL-INSUFFICIENCY; CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; QUALITY-OF-CARE; CONVERTING-ENZYME INHIBITOR; CARDIOVASCULAR EVENTS; SERUM CREATININE; CKD; NEPHROPATHY; DEFINITION AB Background: Because serum creatinine is an insensitive measure of kidney dysfunction, guidelines have advocated routine use of estimated glomerular filtration rate (eGFR) to identify patients with chronic kidney disease (CKD). Patients with early (stage 3) CKD remain undiagnosed in primary care clinics; therefore, we hypothesized that routine reporting of eGFR in outpatient clinics would improve the recognition and treatment of CKD. Methods: A retrospective review of primary care patients was undertaken at the Bronx Veterans Affairs Medical Center, Bronx, New York, before and after the institution of routine eGFR reporting. We evaluated the achievement of diagnostic and therapeutic treatment goals based on the Kidney Disease Outcomes Quality Initiative guidelines (documentation of CKD, urinalysis assessment, blood pressure < 130/80 mm Hg, and renin-angiotensin system blockade) for patients with stage 3 CKD during each period. Results: Overall, patients with diabetes with early-stage CKD achieved superior treatment rates than similar patients without diabetes. Routine reporting of eGFR improved the documentation and identification of CKD by almost 50%, although absolute improvement was modest. Use of renin-angiotensin system blockers improved minimally, as did blood pressure control. Patients with documented CKD achieved treatment goals more frequently than patients without documented CKD. Conclusion: Routine reporting of eGFR alone modestly improved the identification of patients with CKD without a clinically significant effect on care. For Modification of Diet in Renal Disease Study calculation of eGFR reporting to effect improvements in CKD care, it will be necessary to pair eGFR reporting with provider education to identify these patients and treat them effectively. C1 CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Highland Hosp, Dept Med, Rochester, NY 14620 USA. Bronx Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. RP Rohatgi, R (reprint author), CUNY Mt Sinai Sch Med, Dept Med, Box 1243,1 Gustave L Levy Pl, New York, NY 10029 USA. EM rajeev.rohatgi@mssm.edu NR 27 TC 46 Z9 47 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2007 VL 49 IS 5 BP 634 EP 641 DI 10.1053/j.ajkd.2007.02.258 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 197QG UT WOS:000248570100011 PM 17472845 ER PT J AU Aspinall, SL Metlay, JP Maselli, JH Gonzales, R AF Aspinall, Sherrie L. Metlay, Joshua P. Maselli, Judith H. Gonzales, Ralph TI Impact of hospital formularies on fluoroquinolone prescribing in emergency departments SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 06-09, 2005 CL San Francisco, CA SP Infect Dis Soc Amer ID COMMUNITY-ACQUIRED PNEUMONIA; RESISTANT STREPTOCOCCUS-PNEUMONIAE; RESPIRATORY-TRACT INFECTIONS; UNITED-STATES; RISK-FACTORS; CLOSTRIDIUM-DIFFICILE; EDUCATIONAL-METHODS; ANTIBIOTIC-THERAPY; MANAGEMENT; MORTALITY AB Objective: To examine factors associated with fluoroquinolone prescribing among adults receiving antibiotics for acute respiratory tract infections (ARIs) in emergency departments. Study Design: Cross-sectional. Methods: We analyzed data from 8 Department of Veterans Affairs medical centers and 7 nonfederal US hospitals. At each hospital, we randomly sampled 200 ARI visits with International Classification of Diseases, Ninth Revision discharge diagnoses for nonspecific upper respiratory infections, acute bronchitis, pharyngitis, sinusitis, and pneumonia between November 1, 2003, and February 29, 2004. Patient and provider factors associated with each visit were extracted from medical records. System characteristics were obtained by surveying pharmacy directors. Multivariate logistic regression was used to evaluate independent predictors of fluoroquinolone prescribing. Results: Fluoroquinolones accounted for 14% of these prescriptions. At hospitals with at least 1 unrestricted fluoroquinolone on formulary (n = 12) , the average fluoroquinolone prescription rate was 17%, compared with a 6% prescription rate at hospitals were fluoroquinolone access was restricted by the hospital formulary (n = 3) (P < .0001). Factors associated with increased fluoroquinolone prescription rates were hospital admission (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.1, 3.1) and the diagnoses of acute bronchitis (OR = 2.3; 95% CI = 1.3, 4.2), acute exacerbations of chronic bronchitis (OR = 2.6; 95% CI = 1.2, 5.6), and pneumonia (OR = 6.4; 95% CI = 3.3. 12.4). Restricted hospital status was associated with decreased fluoroquinolones accounted for 14% of the antibiotic prescriptions. Conclusions: Hospital formulary policies represent a potentially important target for influencing out-patient drug prescribing in emergency departments. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. Philadelphia VA Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot 151C U, Univ Dr C, Pittsburgh, PA 15240 USA. EM sherrie.aspinall@va.gov FU AHRQ HHS [R01-HS13915] NR 32 TC 5 Z9 5 U1 0 U2 0 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD MAY PY 2007 VL 13 IS 5 BP 241 EP 248 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 169AI UT WOS:000246564700005 PM 17488189 ER PT J AU Bendavid, E Kaganova, Y Needleman, J Gruenberg, L Weissman, JS AF Bendavid, Eran Kaganova, Yevgenia Needleman, Jack Gruenberg, Leonard Weissman, Joel S. TI Complication rates on weekends and weekdays in US hospitals SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE complications; weekends; working conditions; logistic modeling; quality of health care; Agency for Healthcare Research and Quality ID INTENSIVE-CARE-UNIT; PATIENT-SAFETY; COMORBIDITY MEASURES; ANESTHETIC MISHAPS; MORTALITY; SERVICE; ADMISSION; OUTCOMES AB PURPOSE: Recent studies and anecdotal evidence suggest that patient safety may be compromised on weekends. Our objective was to determine whether rates of complications in hospitals are higher on weekends than on weekdays. METHODS: We examined records from 4,967,114 admissions to acute care hospitals in 3 states and analyzed complication rates using the Patient Safety Indicators. We selected 8 indicators that could be assigned to a single day: complications of anesthesia, retained foreign bodies, postoperative hemorrhage, accidental cuts and lacerations during procedures, birth trauma, obstetric trauma during vaginal deliveries with and without instrumentation, and obstetric trauma during cesarean delivery. Odds ratios (ORs) comparing weekends versus weekdays were adjusted for demographics, type of admission, and admission route. In a subgroup analysis of surgical complications, we restricted the population to patients who underwent cardiac or vascular procedures. RESULTS: Four of the 8 complications occurred more frequently on weekends: postoperative hemorrhage ( OR 1.07, 95% confidence interval [CI], 1.01-1.14), newborn trauma ( OR 1.06, 95% CI, 1.03-1.10), vaginal deliveries without instrumentation ( OR 1.03, 95% CI, 1.02-1.04), and obstetric trauma during cesarean sections ( OR 1.36, 95% CI, 1.29-1.44). Complications related to anesthesia occurred less frequently on weekends ( OR 0.86). Among patients undergoing vascular procedures, surgical complications occurred more frequently on weekends ( OR 1.46, 95% CI, 1.16-1.85). CONCLUSIONS: Rates of complications are marginally higher on weekends than on weekdays for some surgical and newborn complications, but more significantly for obstetric trauma and for surgical complications involving patients undergoing vascular procedures. Hospitals should work toward increasing the robustness of safeguards on weekends. (c) 2007 Elsevier Inc. All rights reserved. C1 Stanford Univ, Sch Med, Ctr Hlth Policy, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. Univ Massachusetts, Long Term Care Data Inst, Boston, MA 02125 USA. Univ Massachusetts, Dept Gerontol, Boston, MA 02125 USA. RP Bendavid, E (reprint author), Stanford Univ, Sch Med, Ctr Hlth Policy, 117 Encina Commons, Stanford, CA 94305 USA. EM ebd@stanford.edu RI Needleman, Jack/I-5461-2013 OI Needleman, Jack/0000-0002-2875-0589 NR 40 TC 39 Z9 39 U1 1 U2 6 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 MAY PY 2007 VL 120 IS 5 BP 422 EP 428 DI 10.1016/j.amjmed.2006.05.067 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 162BQ UT WOS:000246061900012 PM 17466653 ER PT J AU Siegel, AJ Verbalis, JG Clement, S Mendelson, JH Mello, NK Adner, M Shirey, T Glowacki, J Lee-Lewandrowski, E Lewandrowski, KB AF Siegel, Arthur J. Verbalis, Joseph G. Clement, Stephen Mendelson, Jack H. Mello, Nancy K. Adner, Marvin Shirey, Terry Glowacki, Julie Lee-Lewandrowski, Elizabeth Lewandrowski, Kent B. TI Hyponatremia in marathon runners due to inappropriate arginine vasopressin secretion SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE arginine vasopressin; exercise-associated hyponatremia; hypertonic (3%) saline; interleukin-6; rhabdomyolysis; syndrome of inappropriate antidiuretic hormone secretion ID EXERCISE-ASSOCIATED HYPONATREMIA; ATRIAL-NATRIURETIC-PEPTIDE; HOSPITALIZED-PATIENTS; NEUROHYPOPHYSEAL SECRETION; CIRCULATING CYTOKINES; ANTIDIURETIC HORMONE; ENDURANCE EXERCISE; WATER-INTOXICATION; RISK-FACTORS; ENCEPHALOPATHY AB PURPOSE: Exercise- associated hyponatremia ( EAH), as defined by a blood sodium concentration [Na+] less than 135 mmol/ L, may lead to hypotonic encephalopathy with fatal cerebral edema. Understanding the pathogenetic role of antidiuresis may lead to improved strategies for prevention and treatment. METHODS: Normonatremic marathon runners were tested pre- and post- race for creatine kinase, interleukin-6, cortisol, prolactin, and arginine vasopressin. Similar testing also was carried out in runners with encephalopathy caused by EAH, including 2 cases with fatal cerebral edema. RESULTS: Normonatremic runners ( n = 33; 2001) with a mean 3% decrease in body weight showed a 40- fold increase in interleukin- 6 ( 66.6 +/- 11.9 pg/ mL from 1.6 +/- 0.5 pg/ mL, P =. 001), which was significantly correlated with increases in creatine kinase ( r = 0.88, P=<. 0001), cortisol ( r = 0.70, P =. 0003), and prolactin ( r = 0.67, P =<. 007), but not arginine vasopressin ( r= 0.44, P =.07). Collapsed runners with EAH ( n = 22; 2004) showed a mean blood urea nitrogen less than 15 mg/ dL with measurable plasma levels of arginine vasopressin ( > 0.5 pg/ mL) in 43% of cases. Two marathon runners with fatal cerebral edema additionally showed less than maximally dilute urines ( > 100 mmol/ kg/ H2O) and urine [ Na+] greater than 25 mEq/ L. CONCLUSIONS: Cases of EAH fulfill the essential diagnostic criteria for the syndrome of inappropriate antidiuretic hormone secretion ( SIADH). Runners with hypotonic encephalopathy at subsequent races were treated with intravenous hypertonic ( 3%) saline on the basis of this paradigm, which resulted in rapid clinical improvement without adverse effects. Release of muscle- derived interleukin- 6 may play a role in the nonosmotic secretion of arginine vasopressin, thereby linking rhabdomyolysis to the pathogenesis of EAH. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. McLean Hosp, Dept Med, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Georgetown Univ, Med Ctr, Dept Med, Washington, DC USA. Metrow Med Ctr, Framingham, MA USA. Nova Biomed Inc, Waltham, MA USA. Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Gray 5,Fruit St, Boston, MA 02114 USA. EM klewandrowski@partners.org NR 56 TC 6 Z9 6 U1 0 U2 6 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 MAY PY 2007 VL 120 IS 5 DI 10.1016/j.amjmed.2006.10.027 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 162BQ UT WOS:000246061900021 ER PT J AU Rosenbloom, MH Singhal, AB AF Rosenbloom, M. H. Singhal, A. B. TI CT angiography and diffusion-perfusion MR imaging in a patient with ipsilateral reversible cerebral vasoconstriction after carotid endarterectomy SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID POSTPARTUM ANGIOPATHY AB Reversible cerebral vasoconstriction syndromes (RCVS) typically affect the bilateral medium-sized intracerebral arteries and their branches. We describe a woman with RCVS restricted to the ipsilateral hemisphere after carotid endarterectomy. Serial CT angiography proved useful in documenting vasoconstriction. Perfusion MR imaging showed hypoperfusion in the deep watershed regions of the ipsilateral cerebral arteries but relatively normal perfusion in superficial cortical regions. Diffusion MR imaging showed progressive borderzone infarcts. These novel imaging findings provide insights into the pathophysiology of stroke in RCVS. C1 Massachusetts Gen Hosp, Stroke Res Ctr, Dept Neurol, Boston, MA 02114 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Stroke Res Ctr, Dept Neurol, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM asinghal@partners.org NR 10 TC 20 Z9 23 U1 1 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 2007 VL 28 IS 5 BP 920 EP 922 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 169ON UT WOS:000246601600033 PM 17494670 ER PT J AU Phillips-Edwards, A Collins-Smith, R Del Rio, GC Brown, C Wu, L Singh, H AF Phillips-Edwards, Althea Collins-Smith, Ruth Del Rio, Gustavo Camacho Brown, Carmen Wu, Louis Singh, Hardeep TI 'ALLHAT' and innovations in nursing SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material ID BLOOD-PRESSURE-MEASUREMENT; LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; PRIMARY-CARE; SPHYGMOMANOMETERS; SUBCOMMITTEE; HYPERTENSION; COMMITTEE C1 Michael E DeBakey Vet Affairs Med Ctr, Primary Care Sect, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Gen Med Sect, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Phillips-Edwards, A (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Primary Care Sect, Houston, TX USA. EM Phillips-Edwards.Althea@houston.med.va.gov NR 23 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD MAY PY 2007 VL 107 IS 5 BP 72C EP + PG 5 WC Nursing SC Nursing GA 166NC UT WOS:000246384700031 ER PT J AU Hasler, U AF Hasler, Udo TI Interplay between TonEBP and calcineurin-NFATc signaling pathways: a means of optimizing water reabsorption? Focus on "Calcineurin-NFATc signaling pathway regulates AQP2 expression in response to calcium signals and osmotic stress" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Editorial Material ID ENHANCER-BINDING PROTEIN; TRANSCRIPTIONAL ACTIVATOR; STIMULATES TRANSCRIPTION; HYPERTONICITY; NEPHROTOXICITY; AQUAPORINS; KIDNEY; CELLS C1 Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA. RP Hasler, U (reprint author), Div Nephrol, Prog Membrane Biol, Simches Res Bldg,185 Cambridge St,Suite 8202, Boston, MA 02114 USA. EM uhasler@partners.org NR 16 TC 1 Z9 1 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 2007 VL 292 IS 5 BP C1581 EP C1582 DI 10.1152/ajpcell.00008.2007 PG 2 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 188RH UT WOS:000247936500002 PM 17215329 ER PT J AU Sakata, S Lebeche, D Sakata, N Sakata, Y Chemaly, ER Liang, LF Takewa, Y Jeong, D Park, WJ Kawase, Y Hajjar, RJ AF Sakata, Susumu Lebeche, Djamel Sakata, Naoya Sakata, Yuri Chemaly, Elie R. Liang, Li Fan Takewa, Yoshiaki Jeong, Dongtak Park, Woo Jin Kawase, Yoshiaki Hajjar, Roger J. TI Targeted gene transfer increases contractility and decreases oxygen cost of contractility in normal rat hearts SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE contractile function; energetics; oxygen consumption; SERCA2a ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; CARDIAC-HYPERTROPHY; PRESSURE-OVERLOAD; FAILURE; EXPRESSION; SERCA2A; ATPASE; MODEL; OVEREXPRESSION; CARDIOMYOPATHY AB The aim of this study was to examine how global cardiac gene transfer of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) can influence left ventricular (LV) mechanical and energetic function, especially in terms of O-2 cost of LV contractility, in normal rats. Normal rats were randomized to receive an adenovirus carrying the SERCA2a (SERCA) or beta-galactosidase (beta-Gal) gene or saline by a catheter-based technique. LV mechanical and energetic function was measured in cross-circulated heart preparations 2-3 days after the infection. The end-systolic pressure-volume relation was shifted upward, end-systolic pressure at 0.1 ml of intraballoon water volume was higher, and equivalent maximal elastance, i.e., enhanced LV contractility, was higher in the SERCA group than in the normal, beta-Gal, and saline groups. Moreover, the LV relaxation rate was faster in the SERCA group. There was no significant difference in myocardial 02 consumption per beat-systolic pressure-volume area relation among the groups. Finally, O-2 cost of LV contractility was decreased to subnormal levels in the SERCA group but remained unchanged in the beta-Gal and saline groups. This lowered O-2 cost of LV contractility in SERCA hearts indicates energy saving in Ca2+ handling during excitation-contraction coupling. Thus overexpression of SERCA2a transformed the normal energy utilization to a more efficient state in Ca2+ handling and superinduced the supranormal contraction/relaxation due to enhanced Ca2+ handling. C1 Mt Sinai Sch Med, New York, NY 10029 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA USA. Nara Med Univ, Sch Med, Dept Physiol 2, Kashihara, Nara 634, Japan. Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea. RP Hajjar, RJ (reprint author), Mt Sinai Sch Med, Atran Lab Bldg, Fifth Floor, Room AB5-02, One, New York, NY 10029 USA. EM roger.hajar@mssm.edu FU NHLBI NIH HHS [HL 057263, HL 071763, R01 HL 078691, HL 083156, K01 HL 076659, HL 080498] NR 27 TC 23 Z9 24 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 2007 VL 292 IS 5 BP H2356 EP H2363 DI 10.1152/ajpheart.01310.2006 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 186KI UT WOS:000247777200041 PM 17220178 ER PT J AU Yi, XH Bouley, R Lin, HY Bechoua, S Sun, TX del Re, E Shioda, T Raychowdhury, MK Lu, HAJ Abou-Samra, AB Brown, D Ausiello, DA AF Yi, Xianhua Bouley, Richard Lin, Herbert Y. Bechoua, Shaliha Sun, Tian-xiao del Re, Elisabetta Shioda, Toshi Raychowdhury, Malay K. Lu, Hua A. J. Abou-Samra, Abdul B. Brown, Dennis Ausiello, Dennis A. TI Alix (AIP1) is a vasopressin receptor (V2R)-interacting protein that increases lysosomal degradation of the V2R SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE LLC-PK1 renal epithelial cells; G protein-coupled receptors; receptor-mediated endocytosis; antidiuretic hormone; yeast two-hybrid screening; protein interaction ID CLATHRIN-MEDIATED ENDOCYTOSIS; BETA-ADRENERGIC-RECEPTOR; COUPLED RECEPTORS; DOWN-REGULATION; MULTIVESICULAR BODY; BINDING PARTNER; CELLS; RESENSITIZATION; INTERNALIZATION; COMPLEXES AB The vasopressin type 2 receptor (V2R) is a G protein-coupled receptor that plays a central role in renal water reabsorption. Termination of ligand (vasopressin) stimulation is an important physiological regulatory event, but few proteins that interact with the V2R during downregulation after vasopressin (VP) binding have been identified. Using yeast two-hybrid screening of a human kidney cDNA library, we show that a 100-kDa protein called ALG-2-interacting protein X (Alix) interacts with the last 29 amino acids of the V2R COOH terminus. This was confirmed by pull-down assays using a GST-V2R-COOH-tail fusion protein. Alix was immunolocalized in principal cells of the kidney, which also express the V2R. The function of the Alix-V2R interaction was studied by transfecting Alix into LLC-PK1 epithelial cells expressing V2R-green fluorescent protein (GFP). Under basal conditions, V2R-GFP localized mainly at the plasma membrane. On VP treatment, V2R-GFP was internalized into perinuclear vesicles in the nontransfected cells. In contrast, V2R-GFP fluorescence was virtually undetectable 2 h after exposure to VP in cells that coexpressed Alix. Western blotting using an anti-GFP antibody showed marked degradation of the V2R after 2 h in the presence of VP and Alix, a time point at which little or no degradation was detected in the absence of Alix. In contrast, little or no degradation of the parathyroid hormone receptor was detectable in the presence or absence of Alix and/or the PTH ligand. The VP-induced disappearance of V2R-GFP was abolished by chloroquine, a lysosomal degradation inhibitor, but not by MG132, a proteosome inhibitor. These data suggest that Alix increases the rate of lysosomal degradation of V2R and may play an important regulatory role in the VP response by modulating V2R downregulation. C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bouley, R (reprint author), Div Nephrol, Program Membrane Biol, 185 Cambridge St,CPZN 8150, Boston, MA 02114 USA. EM Bouley@receptor.mgh.harvard.edu OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NCI NIH HHS [CA-082230]; NIDDK NIH HHS [DK-19406, DK-38452, DK-57521, K8-DK-075940-01, DK-43341, DK11794, K08 DK-02716] NR 51 TC 11 Z9 11 U1 0 U2 0 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 MAY PY 2007 VL 292 IS 5 BP F1303 EP F1313 DI 10.1152/ajprenal.00441.2005 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 188SU UT WOS:000247940400001 PM 17287200 ER PT J AU Viswanath, K Kreuter, MW AF Viswanath, K. Kreuter, Matthew W. TI Health disparities, communication inequalities, and eHealth SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material DE u ID INFORMATION C1 Dana Farber Canc Inst, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA. RP Viswanath, K (reprint author), Dana Farber Canc Inst, Dept Soc Human Dev & Hlth, LW 630,44 Binney St, Boston, MA 02115 USA. EM vish_viswanath@dfci.harvard.edu FU NCI NIH HHS [R01 CA122894, R01 CA122894-01] NR 6 TC 57 Z9 58 U1 1 U2 13 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 MAY PY 2007 VL 32 IS 5 SU S BP S131 EP S133 DI 10.1016/j.amepre.2007.02.012 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 168LX UT WOS:000246527200010 PM 17466818 ER PT J AU Wisniewski, SR Fava, M Trivedi, MH Thase, ME Warden, D Niederehe, G Friedman, ES Biggs, MM Sackeim, HA Shores-Wilson, K McGrath, PJ Lavori, PW Miyahara, S Rush, AJ AF Wisniewski, Stephen R. Fava, Maurizio Trivedi, Madhukar H. Thase, Michael E. Warden, Diane Niederehe, George Friedman, Edward S. Biggs, Melanie M. Sackeim, Harold A. Shores-Wilson, Kathy McGrath, Patrick J. Lavori, Philip W. Miyahara, Sachiko Rush, A. John TI Acceptability of second-step treatments to depressed outpatients: A STAR*D report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; MEDICATION ALGORITHM PROJECT; ILLNESS RATING-SCALE; REPORT QIDS-SR; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; SYMPTOMATOLOGY IDS; DISORDER; RATIONALE AB Objective: Treatment of major depressive disorder typically entails implementing treatments in a stepwise fashion until a satisfactory outcome is achieved. This study sought to identify factors that affect patients' willingness to accept different second-step treatment approaches. Method: Participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial who had unsatisfactory outcomes after initial treatment with citalopram were eligible for a randomized second-step treatment trial. An equipoise-stratified design allowed participants to exclude or include specific treatment strategies. Analyses were conducted to identify factors associated with the acceptability of the following second-step treatments: cognitive therapy versus no cognitive therapy, any switch strategy versus any augmentation strategy (including cognitive therapy), and a medication switch strategy only versus a medication augmentation strategy only. Results: Of the 1,439 participants who entered second-step treatment, 1% accepted all treatment strategies, 3% accepted only cognitive therapy, and 26% accepted cognitive therapy (thus, 71% did not accept cognitive therapy). Those with higher educational levels or a family history of a mood disorder were more likely to accept cognitive therapy. Participants in primary care settings and those who experienced a greater side effect burden or a lower reduction in symptom severity with citalopram were more likely to accept a switch strategy as compared with an augmentation strategy. Those with concurrent drug abuse and recurrent major depressive disorder were less likely to accept a switch strategy. Conclusions: Few participants accepted all treatments. Acceptance of cognitive therapy was primarily associated with sociodemographic characteristics, while acceptance of a treatment switch was associated with the results of the initial treatment. C1 Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ Pittsburgh, Dept Psychiat, Med Ctr, Pittsburgh, PA 15261 USA. NIMH, Bethesda, MD 20892 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. VA Cooperat Studies Program, Palo Alto, CA USA. Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Wisniewski, SR (reprint author), Univ Pittsburgh, Epidemiol Data Ctr, Grad Sch Publ Hlth, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. RI Biggs, Dr. Melanie/C-1468-2010; McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH-90003] NR 23 TC 47 Z9 47 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2007 VL 164 IS 5 BP 753 EP 760 DI 10.1176/appi.ajp.164.5.753 PG 8 WC Psychiatry SC Psychiatry GA 166HR UT WOS:000246370300015 PM 17475734 ER PT J AU Lucey, BC Varghese, JC Hochberg, A Blake, MA Soto, JA AF Lucey, Brian C. Varghese, Jose C. Hochberg, Aaron Blake, Michael A. Soto, Jorge A. TI CT-Guided intervention with low radiation dose: Feasibility and experience SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE biopsy; CT technique; interventional radiology; radiation dose ID LUNG-CANCER; FLUOROSCOPY; COLONOGRAPHY; REDUCTION; BIOPSIES; GUIDANCE; PATIENT; LESIONS AB OBJECTIVE. The purpose of this study was to evaluate the feasibility of performing CT-guided interventional procedures with a very low radiation dose. MATERIALS AND METHODS. We performed 291 CT-guided interventional procedures using a low dose of radiation. The subjects were 165 men and 126 women 22 - 89 years old with a mean age of 65 years. CT fluoroscopy was not used. The procedures were 201 percutaneous biopsies and 90 percutaneous aspiration or drainage procedures. Before the procedure, images were obtained with standard mAs of 175 - 250 mAs. All subsequent CT was performed at a reduced mAs. Technical success of catheter placement and biopsy was calculated, and the results were compared with those of procedures performed over the previous 12 months with standard radiation doses. Patient weight, lesion size, and number of CT acquisitions needed to complete the procedure were recorded. RESULTS. All but three aspiration or drainage procedures performed at 30 mAs were successful, for a success rate of 96.7%. The technical success rate of biopsy performed at 30 mAs was 93.5%. In the cases of 13 patients undergoing biopsy, the masses were not identified with low-dose technique, and these procedures were completed at a higher dose. Results were independent of patient weight and lesion size. The technical success rate was 98% for percutaneous drainage performed at a standard radiation dose in the 12 months before introduction of the low-dose technique. The technical success rate was 87.5% for biopsy performed at a standard radiation dose in the 12 months before introduction of the low-dose technique. The complication rate of the low-dose technique was comparable to that of the standard-dose technique. CONCLUSION. Low-dose radiation technique using 30 mAs results in technical success for both catheter placement and percutaneous biopsy comparable to standard radiation dose. C1 Boston Univ, Med Ctr, Dept Radiol, Div Body Imaging, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA 02114 USA. RP Lucey, BC (reprint author), Boston Univ, Med Ctr, Dept Radiol, Div Body Imaging, 88 E Newton St,Atrium 2, Boston, MA 02118 USA. OI Soto, Jorge/0000-0003-2533-3015 NR 17 TC 19 Z9 22 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2007 VL 188 IS 5 BP 1187 EP 1194 DI 10.2214/AJR.06.0378 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161KE UT WOS:000246013000012 PM 17449757 ER PT J AU Wittram, C AF Wittram, Conrad TI How I do it: CT pulmonary angiography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chest; CT arteriography; CT technique; embolism ID DISPLAY WINDOW SETTINGS; HELICAL CT; SPIRAL CT; PORCINE MODEL; COMPUTED-TOMOGRAPHY; EMBOLISM; DIAGNOSIS; ARTERIOGRAPHY; OPTIMIZATION; ENHANCEMENT AB OBJECTIVE. The purpose of this article is to describe the techniques to improve motion artifacts, vascular enhancement, flow artifacts, body habitus image noise, vascular opacification in parenchymal lung disease, streak artifacts, and the indeterminate CT pulmonary angiogram. In addition, this article will illustrate the diagnostic criteria of acute and chronic pulmonary emboli. CONCLUSION. Pulmonary embolism is the third most common acute cardiovascular disease, after myocardial infarction and stroke, and it leads to thousands of deaths each year because it often goes undetected. For the more than 25 years that the direct signs of pulmonary embolism have been available to the radiologist on CT, this noninvasive technique has produced a paradigm shift that has raised the standard of care for patients with this disease. C1 Massachusetts Gen Hosp, Dept Thorac Radiol, Boston, MA 02114 USA. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Dept Thorac Radiol, Founders 202,55 Fruit St, Boston, MA 02114 USA. NR 39 TC 53 Z9 66 U1 0 U2 1 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 MAY PY 2007 VL 188 IS 5 BP 1255 EP 1261 DI 10.2214/AJR.06.1104 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161KE UT WOS:000246013000023 PM 17449768 ER PT J AU Shah, ZK McKernan, MG Hahn, PF Sahani, DV AF Shah, Zarine K. McKernan, Margaret G. Hahn, Peter F. Sahani, Dushyant V. TI Enhancing and expansile portal vein thrombosis: Value in the diagnosis of hepatocellular carcinoma in patients with multiple hepatic lesions SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE abdominal imaging; cancer; liver disease ID STAGING SYSTEMS; CIRRHOSIS; COHORT; CLIP AB OBJECTIVE. The objective of this study was to determine whether the presence of enhancing and expansile portal vein thrombus is suggestive of the diagnosis of hepatocellular carcinoma. CONCLUSION. In the presence of hepatic tumors, enhancing expansile portal vein thrombus is highly suggestive of hepatocellular carcinoma. C1 Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org RI Shah, Zarine/E-4064-2011 OI Shah, Zarine/0000-0002-0354-9678 NR 13 TC 27 Z9 29 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 MAY PY 2007 VL 188 IS 5 BP 1320 EP 1323 DI 10.2214/AJR.06.0134 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161KE UT WOS:000246013000032 PM 17449777 ER PT J AU Chang, DS Barack, BM Lee, MH Lee, HY AF Chang, Donald S. Barack, Bruce M. Lee, Margaret H. Lee, Hsin-Yi TI Congenitally corrected transposition of the great arteries: Imaging with 16-MDCT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE angiography; cardiac imaging; cardiovascular disease; congenital; CT ID ANATOMY; ADULT; VENTRICLE C1 VA Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Imaging Serv, Los Angeles, CA 90073 USA. Olive View UCLA Med Ctr, Dept Radiol, Sylmar, CA 91342 USA. RP Chang, DS (reprint author), VA Greater Los Angeles Healthcare Syst, Div Cardiol, 11301 Wilshire Blvd 111E, Los Angeles, CA 90073 USA. EM dchang@ucla.edu NR 9 TC 6 Z9 6 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 MAY PY 2007 VL 188 IS 5 BP W428 EP W430 DI 10.2214/AJR.05.0636 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 161KE UT WOS:000246013000052 PM 17449738 ER PT J AU Asrani, A Kaewlai, R Sacknoff, R Abujudeh, H Novelline, R AF Asrani, A. Kaewlai, R. Sacknoff, R. Abujudeh, H. Novelline, R. TI Scapular Fractures Revisited: Plain Radiograph and MDCT Imaging with 3D Reformations SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Asrani, A.; Kaewlai, R.; Sacknoff, R.; Abujudeh, H.; Novelline, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM aasrani@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900583 ER PT J AU Chatterji, M Lee, SI Dreyer, K Thrall, JH Hahn, PF AF Chatterji, M. Lee, S., I Dreyer, K. Thrall, J. H. Hahn, P. F. TI Radiologist Recommendation for Follow-up Exams: What are the Common Reasons? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Chatterji, M.; Lee, S., I; Dreyer, K.; Thrall, J. H.; Hahn, P. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mchatterji@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900039 ER PT J AU Gutierrez, AJ Freitas, AD Modarresi, S Masih, S AF Gutierrez, A. J. Freitas, A. D. Modarresi, S. Masih, S. TI Radiologic-Orthopedic Correlation of Laymen Terms for Sports Injuries SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Gutierrez, A. J.] Univ Calif Los Angeles, Med Ctr, Dept Radiol, Los Angeles, CA 90024 USA. [Freitas, A. D.; Modarresi, S.; Masih, S.] Vet Adm Greater Los Angeles, Dept Radiol, Los Angeles, CA USA. EM agut95@gmail.com NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900625 ER PT J AU Holalkere, N Guimaraes, AS Hahn, PF Susanna, LI AF Holalkere, N. Guimaraes, A. S. Hahn, P. F. Susanna, L. I. TI Diffusion-weighted MR Imaging (DWI) in Differentiating Benign from Malignant Gynecologic Lesions SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Holalkere, N.; Guimaraes, A. S.; Hahn, P. F.; Susanna, L. I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM nholalkere@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900266 ER PT J AU Holalkere, N Sahani, DV Hadigan, CM Hahn, PF Mueller, PR AF Holalkere, N. Sahani, D., V Hadigan, C. M. Hahn, P. F. Mueller, P. R. TI Role of 1H-MR Spectroscopy in the Evaluation of Hepatic Steatosis and Steatohepatitis in HIV-infected Subjects SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Holalkere, N.; Sahani, D., V; Hadigan, C. M.; Hahn, P. F.; Mueller, P. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM nholalkere@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900224 ER PT J AU Jagannathan, J Ramaiya, N Van den Abbeele, A AF Jagannathan, J. Ramaiya, N. Van den Abbeele, A. TI Missed Metastases-Causes and Clinical Relevance SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Jagannathan, J.; Ramaiya, N.; Van den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM jjagannathan@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900424 ER PT J AU Jagannathan, J Ramaiya, N Van den Abbeele, A AF Jagannathan, J. Ramaiya, N. Van den Abbeele, A. TI Malignant Melanoma - Not Just Skin Deep! SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Jagannathan, J.; Ramaiya, N.; Van den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM jjagannathan@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900419 ER PT J AU Jati, A Ji, H Ramaiya, N AF Jati, A. Ji, H. Ramaiya, N. TI Mesenteric Masses and Their Differentiating Characteristics SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Ji, H.; Ramaiya, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jati, A.] VA Med Ctr, W Roxbury, MA USA. EM anupmajati@yahoo.com NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900470 ER PT J AU Ji, H Fennessy, F Van den Abbeele, A Ros, P AF Ji, H. Fennessy, F. Van den Abbeele, A. Ros, P. TI Focal Gastrointestinal Tracer Uptake on the 18F FDG PET/CT in Patients with Lymphoma: Differentiation of Lymphoma from Other Conditions SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Ji, H.; Fennessy, F.; Van den Abbeele, A.; Ros, P.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Radiol, Boston, MA 02115 USA. EM hji@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900489 ER PT J AU Ji, H Ramaiya, N Khosa, F Van den Abbeele, A AF Ji, H. Ramaiya, N. Khosa, F. Van den Abbeele, A. TI Primary Malignant Neoplasms Mimicking Peritoneal Carcinomatosis: CT, MRI, and 18F FDG PET/CT Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Ji, H.; Ramaiya, N.; Khosa, F.; Van den Abbeele, A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiol, Boston, MA 02115 USA. EM hji@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900485 ER PT J AU Ji, H Ramaiya, N Israel, D Ros, P AF Ji, H. Ramaiya, N. Israel, D. Ros, P. TI Extranodal Manifestations of Lymphoma in the Abdomen SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Ji, H.; Ramaiya, N.; Israel, D.; Ros, P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol,Brigham & Womens Hosp, Boston, MA 02115 USA. EM hji@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900414 ER PT J AU Johnston, C Ramaiya, N Sheehy, N Khosa, F Van den Abbeele, A AF Johnston, C. Ramaiya, N. Sheehy, N. Khosa, F. Van den Abbeele, A. TI Radiological Response and Toxicity of the New Targeted Molecular Therapies for Cancer-What the Radiologist Needs to Know SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Johnston, C.; Ramaiya, N.; Sheehy, N.; Khosa, F.; Van den Abbeele, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM ciaranjohnston@yahoo.co.uk NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900696 ER PT J AU Katkar, AS Braschi, M Hahn, PF Seethamraju, RT Harisinghani, MG AF Katkar, A. S. Braschi, M. Hahn, P. F. Seethamraju, R. T. Harisinghani, M. G. TI Variation in the Size of Lymph Nodes on Pre and Postcontrast Nanoparticle-enhanced MRI SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Katkar, A. S.; Braschi, M.; Hahn, P. F.; Harisinghani, M. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seethamraju, R. T.] Siemens Med Solut, Charlestown, MA USA. EM akatkar@partners.org NR 0 TC 0 Z9 0 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 MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900156 ER PT J AU Khosa, F Ramaiya, N Johnston, C Disalvo, D Jagannathan, J Den Abbeele, AA AF Khosa, F. Ramaiya, N. Johnston, C. Disalvo, D. Jagannathan, J. Den Abbeele, An A. TI Imaging of Venous Thrombosis in Oncologic Patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Meeting Abstract C1 [Khosa, F.; Ramaiya, N.; Johnston, C.; Disalvo, D.; Jagannathan, J.; Den Abbeele, An A.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM fkhosa@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2007 VL 188 IS 5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V04XA UT WOS:000207089900415 ER EF