FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Watson, GS Craft, S AF Watson, GS Craft, S TI Insulin resistance, inflammation, and cognition in Alzheimer's Disease: Lessons for multiple sclerosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Cognitive Decline in Multiple Sclerosis CY NOV 11-13, 2004 CL Taormina, ITALY SP European Charcot Fdn DE Alzheimer's disease; cognition; diabetes; inflammation; insulin; insulin resistance; multiple sclerosis; PPAR gamma ID PROLIFERATOR-ACTIVATED RECEPTOR; AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; IMPAIRED GLUCOSE-TOLERANCE; APOLIPOPROTEIN-E GENOTYPE; NECROSIS-FACTOR-ALPHA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; STREPTOZOTOCIN-DIABETIC RATS; BLOOD-BRAIN-BARRIER AB Insulin resistance (reduced ability of insulin to stimulate glucose utilization) is common in North American and Europe, where as many as one third of all older adults suffer from prodromal or clinical type 2 diabetes mellitus. It has long been known that insulin-resistant conditions adversely affect general health status. A growing body of findings suggests that insulin contributes to normal brain functioning and that peripheral insulin abnormalities increase the risk for memory loss and neurodegenerative disorders such as Alzheimer's disease. Potential mechanisms for these effects include insulin's role in cerebral glucose metabolism, peptide regulation, modulation of neurotransmitter levels, and modulation of many aspects of the inflammatory network. An intriguing question is whether insulin abnormalities also influence the pathophysiology of multiple sclerosis (MS), an autoimmune disorder characterized by elevated inflammatory biomarkers, central nervous system white matter lesions, axonal degeneration, and cognitive impairment. MS increases the risk for type I diabetes mellitus. Furthermore, the lack of association between MS and type 2 diabetes may suggest that insulin resistance affects patients with MS and the general population at the same alarming rate. Therefore, insulin resistance may exacerbate phenomena that are common to MS and insulin-resistant conditions, such as cognitive impairments and elevated inflammatory responses. Interestingly, the thiazolidinediones, which are used to treat patients with type 2 diabetes, have been proposed as potential therapeutic agents for both Alzheimer's disease and MS. The agents improve insulin sensitivity, reduce hyperinsulinemia, and exert anti-inflammatory actions. Ongoing studies will determine whether thiazolidinediones improve cognitive functioning for patients with type 2 diabetes or Alzheimer's disease. Future studies are needed to examine the effects of thiazolidinediones on patients with MS. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S182,Dept Psychiat &, Seattle, WA 98108 USA. RP Watson, GS (reprint author), Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr S182,Dept Psychiat &, 1660 S Columbian Way, Seattle, WA 98108 USA. EM gswatson@u.washington.edu FU NIA NIH HHS [R01 AG-10880]; NIDDK NIH HHS [R01 DK-61606] NR 149 TC 51 Z9 51 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUN 15 PY 2006 VL 245 IS 1-2 SI SI BP 21 EP 33 DI 10.1016/j.jns.2005.08.017 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 055PK UT WOS:000238462500005 PM 16631207 ER PT J AU Mainero, C Pantano, P Caramia, F Pozzilli, C AF Mainero, C Pantano, P Caramia, F Pozzilli, C TI Brain reorganization during attention and memory tasks in multiple sclerosis: Insights from functional MRI studies SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Cognitive Decline in Multiple Sclerosis CY NOV 11-13, 2004 CL Taormina, ITALY SP European Charcot Fdn DE functional MRI; neuroplasticity; multiple sclerosis; cognitive impairment; memory; attention ID COMPENSATORY CORTICAL ACTIVATION; SINGLE CLINICAL ATTACK; RELAPSING-REMITTING MS; WORKING-MEMORY; COGNITIVE IMPAIRMENT; MOTOR REORGANIZATION; ALZHEIMERS-DISEASE; FMRI; PATTERNS; DISABILITY AB Deficits in memory and attention frequently occur during the course of multiple sclerosis (MS). In patients with MS the severity of cognitive manifestations is not closely related to indices of structural brain damage on both conventional and non conventional magnetic resonance imaging (MRI). It is conceivable that the ability of the brain to compensate for tissue impairment or loss may contribute to the maintenance of normal performance despite scattered brain lesions. Accordingly, using functional MRI (fMRI), patients with multiple sclerosis showed a greater extent of brain activation during motors tasks than controls. Changes in functional organization of the cerebral cortex have also been reported by fMR1 studies comparing the activation patterns during cognitive tasks in patients with MS and in healthy subjects. Differences in patients' selection, activation paradigm, experimental design and MR acquisition parameters make, however, the results obtained from fMRI studies difficult to be compared and may explain, at least partially, some discrepant findings. Nevertheless, fMRI studies provide a new interesting way of understanding how the brain can change its functional organization in response to MS pathology, and might be useful in the study of the effects of either rehabilitation or pharmacological agents on brain plasticity. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02139 USA. Univ Roma La Sapienza, Dept Neurol Sci, Neurol Sect, Rome, Italy. Univ Roma La Sapienza, Dept Neurol Sci, Sect Neuroradiol, Rome, Italy. RP Mainero, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Cambridge, MA 02139 USA. EM caterina@nmr.mgh.harvard.edu RI Patrizia, Pantano/C-8214-2009 OI Patrizia, Pantano/0000-0001-9659-8294 NR 37 TC 34 Z9 34 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUN 15 PY 2006 VL 245 IS 1-2 SI SI BP 93 EP 98 DI 10.1016/j.jns.2005.08.024 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 055PK UT WOS:000238462500016 PM 16626753 ER PT J AU Stone, ME AF Stone, ME TI Don't leave me this way or when I get back on my feet you'll be sorry. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU REED BUSINESS INFORMATION PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JUN 15 PY 2006 VL 131 IS 11 BP 92 EP 92 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 054VA UT WOS:000238405500211 ER PT J AU Kantarjian, H Giles, F Wunderle, L Bhalla, K O'Brien, S Wassmann, B Tanaka, C Manley, P Rae, P Mietlowski, W Bochinski, K Hochhaus, A Griffin, JD Hoelzer, D Albitar, M Dugan, M Cortes, J Alland, L Ottmann, OG AF Kantarjian, H Giles, F Wunderle, L Bhalla, K O'Brien, S Wassmann, B Tanaka, C Manley, P Rae, P Mietlowski, W Bochinski, K Hochhaus, A Griffin, JD Hoelzer, D Albitar, M Dugan, M Cortes, J Alland, L Ottmann, OG TI Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; IN-VITRO ACTIVITY; BCR-ABL; AMINOPYRIMIDINE INHIBITOR; MESYLATE THERAPY; BLAST CRISIS; PHASE; AMN107 AB BACKGROUND: Resistance to imatinib mesylate can occur in chronic myelogenous leukemia (CML). Preclinical in vitro studies have shown that nilotinib (AMN107), a new BCR-ABL tyrosine kinase inhibitor, is more potent than imatinib against CML cells by a factor of 20 to 50. METHODS: In a phase 1 dose-escalation study, we assigned 119 patients with imatinib-resistant CML or acute lymphoblastic leukemia (ALL) to receive nilotinib orally at doses of 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, and 1200 mg once daily and at 400 mg and 600 mg twice daily. RESULTS: Common adverse events were myelosuppression, transient indirect hyperbilirubinemia, and rashes. Of 33 patients with the blastic phase of disease, 13 had a hematologic response and 9 had a cytogenetic response; of 46 patients with the accelerated phase, 33 had a hematologic response and 22 had a cytogenetic response; 11 of 12 patients with the chronic phase had a complete hematologic remission. CONCLUSIONS: Nilotinib has a relatively favorable safety profile and is active in imatinib-resistant CML. C1 Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Unit 428, Houston, TX 77230 USA. Univ Frankfurt, D-6000 Frankfurt, Germany. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Novartis Pharmaceut, E Hanover, NJ USA. Quest Diagnost, San Juan Capistrano, CA USA. Univ Heidelberg, Fak Klin Med Mannheim, Mannheim, Germany. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Kantarjian, H (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Unit 428, POB 301402, Houston, TX 77230 USA. EM hkantarj@mdanderson.org RI Ottmann, Oliver/D-5007-2016; OI Ottmann, Oliver/0000-0001-9559-1330; Hochhaus, Andreas/0000-0003-0626-0834 NR 26 TC 782 Z9 815 U1 3 U2 29 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 JUN 15 PY 2006 VL 354 IS 24 BP 2542 EP 2551 DI 10.1056/NEJMoa055104 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 052KU UT WOS:000238233400004 PM 16775235 ER PT J AU Wiedemann, HP Wheeler, AP Bernard, GR Thompson, BT Hayden, D deBoisblanc, B Connors, AF Hite, RD Harabin, AL AF Wiedemann, HP Wheeler, AP Bernard, GR Thompson, BT Hayden, D deBoisblanc, B Connors, AF Hite, RD Harabin, AL CA Natl Heart Lung Blood Inst Acute TI Comparison of two fluid-management strategies in acute lung injury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY ILL PATIENTS; PRESSURE PULMONARY-EDEMA; GOAL-DIRECTED THERAPY; OXYGEN DELIVERY; SEPTIC SHOCK; SUPRANORMAL VALUES; PROSPECTIVE TRIAL; PATIENT SAFETY; FUROSEMIDE AB BACKGROUND: Optimal fluid management in patients with acute lung injury is unknown. Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary-organ perfusion. METHODS In a randomized study, we compared a conservative and a liberal strategy of fluid management using explicit protocols applied for seven days in 1000 patients with acute lung injury. The primary end point was death at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days and measures of lung physiology. RESULTS: The rate of death at 60 days was 25.5 percent in the conservative-strategy group and 28.4 percent in the liberal-strategy group (P=0.30; 95 percent confidence interval for the difference, -2.6 to 8.4 percent). The mean (+/-SE) cumulative fluid balance during the first seven days was -136+/-491 ml in the conservative-strategy group and 6992+/-502 ml in the liberal-strategy group (P<0.001). As compared with the liberal strategy, the conservative strategy improved the oxygenation index ([mean airway pressure x the ratio of the fraction of inspired oxygen to the partial pressure of arterial oxygen] x 100) and the lung injury score and increased the number of ventilator-free days (14.6+/-0.5 vs. 12.1+/-0.5, P<0.001) and days not spent in the intensive care unit (13.4+/-0.4 vs. 11.2+/-0.4, P<0.001) during the first 28 days but did not increase the incidence or prevalence of shock during the study or the use of dialysis during the first 60 days (10 percent vs. 14 percent, P=0.06). CONCLUSIONS: Although there was no significant difference in the primary outcome of 60-day mortality, the conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures. These results support the use of a conservative strategy of fluid management in patients with acute lung injury. C1 Cleveland Clin, Dept Pulm Allergy & Crit Care Med, Cleveland, OH 44195 USA. Vanderbilt Univ, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. Wake Forest Univ, Hlth Sci Ctr, Winston Salem, NC 27109 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Wiedemann, HP (reprint author), Cleveland Clin, Dept Pulm Allergy & Crit Care Med, 9500 Euclid Ave,Desk A-90, Cleveland, OH 44195 USA. EM wiedemh@ccf.org OI Wiedemann, Herbert/0000-0002-4587-4401 NR 37 TC 1275 Z9 1353 U1 7 U2 43 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 JUN 15 PY 2006 VL 354 IS 24 BP 2564 EP 2575 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 052KU UT WOS:000238233400006 ER PT J AU Triggs, WJ Harris, NL Menkes, DL Cros, DP Brown, RH AF Triggs, WJ Harris, NL Menkes, DL Cros, DP Brown, RH TI Case 18-2006: A 57-year-old woman with numbness and weakness of the feet and legs - Charcot-Marie-Tooth disease type 2, with Adie's pupil and a mutation in the MPZ gene SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PROTEIN ZERO GENE; SENSORY NEUROPATHY; HEREDITARY MOTOR; PERIPHERAL NEUROPATHY; AXONAL NEUROPATHY; THR124MET; PHENOTYPE; PATHOLOGY; FEATURES; P0 C1 Univ Florida, McKnight Brain Inst, Dept Neurol, Gainesville, FL 32611 USA. Univ Florida, Coll Med, Gainesville, FL USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA. RP Triggs, WJ (reprint author), Univ Florida, McKnight Brain Inst, Dept Neurol, Gainesville, FL 32611 USA. NR 36 TC 4 Z9 7 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 JUN 15 PY 2006 VL 354 IS 24 BP 2584 EP 2592 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 052KU UT WOS:000238233400010 PM 16775239 ER PT J AU Bearden, CE Glahn, DC Monkul, ES Barrett, J Najt, P Villarreal, V Soares, JC AF Bearden, Carrie E. Glahn, David C. Monkul, E. Serap Barrett, Jennifer Najt, Pablo Villarreal, Veronica Soares, Jair C. TI Patterns of memory impairment in bipolar disorder and unipolar major depression SO PSYCHIATRY RESEARCH LA English DT Article DE mood disorder; clinical state; declarative memory; cognition; bipolar depression; unipolar depression ID MOOD DISORDERS; VERBAL MEMORY; COGNITIVE IMPAIRMENT; HIPPOCAMPAL VOLUME; SUSTAINED ATTENTION; DECLARATIVE MEMORY; CLINICAL-FEATURES; EUTHYMIC PATIENTS; RATING-SCALE; ILLNESS AB Unipolar and bipolar depression are known to exert detrimental effects on learning and memory processes. However, few comparisons have been undertaken between bipolar and unipolar patients with comparable illness histories, and predictors of impairment are not well understood. Adult outpatients with unipolar major depressive illness (UP, n = 30) and bipolar disorder (BP, n = 30), group-matched for illness duration and severity of depressive symptomatology (16% clinically remitted, 42% partially remitted, 42% depressed), and 30 demographically matched controls completed measures of general cognitive functioning and declarative memory. Despite comparable general intellectual abilities, BP and UP patients exhibited significant memory deficits relative to healthy controls. A similar deficit profile was observed in both patient groups, involving poorer verbal recall and recognition. Impairments were not secondary to strategic processing deficits or rapid forgetting. Although depression severity was not associated with neurocognitive performance, number of hospitalizations and family history of mood disorder significantly affected memory function in BP, but not UP, patients. Results suggest qualitatively similar patterns of memory impairment in BP and UP patients, consistent with a primary encoding deficit. These impairments do not appear to be secondary to clinical state, but rather suggest a similar underlying pathophysiology involving medial temporal dysfunction. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Schizophrenia & Related Disorders, San Antonio, TX 78229 USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, TR-35340 Izmir, Turkey. Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Bearden, CE (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 Bldg Med Pl,Suite 2265, Los Angeles, CA 90095 USA. EM cbearden@mednet.ucla.edu FU NCRR NIH HHS [M01-RR-01346]; NIMH NIH HHS [MH01736] NR 56 TC 83 Z9 86 U1 1 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 JUN 15 PY 2006 VL 142 IS 2-3 BP 139 EP 150 DI 10.1016/j.psychres.2005.08.010 PG 12 WC Psychiatry SC Psychiatry GA 057WM UT WOS:000238625900003 PM 16631256 ER PT J AU Pelish, HE Ciesla, W Tanaka, N Reddy, K Shair, MD Kirchhausen, T Lencer, WI AF Pelish, HE Ciesla, W Tanaka, N Reddy, K Shair, MD Kirchhausen, T Lencer, WI TI The Cdc42 inhibitor secramine B prevents cAMP-induced K+ conductance in intestinal epithelial cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE secramine; chloride secretion; Cdc42; cAMP; potassium channel regulation; KCNQ1/KCNE3 ID TRANS-GOLGI NETWORK; CHLORIDE SECRETION; CHOLERA-TOXIN; T84 CELLS; PLASMA-MEMBRANE; CL-SECRETION; CYCLIC-AMP; LINE; CHROMANOLS; BLOCKADE AB Cyclic AMP- (CAMP) and calcium-dependent agonists stimulate chloride secretion through the coordinated activation of distinct apical and basolateral membrane channels and ion transporters in mucosal epithelial cells. Defects in the regulation of Cl- transport across mucosal surfaces occur with cystic fibrosis and V. cholerae infection and can be life threatening. Here we report that secramine B, a small molecule that inhibits activation of the Rho GTPase Cdc42, reduced cAMP-stimulated chloride secretion in the human intestinal cell line T84. Secramine B interfered with a cAMP-gated and Ba2+-sensitive K+ channel, presumably KCNQI/KCNE3. This channel is required to maintain the membrane potential that sustains chloride secretion. In contrast, secramine B did not affect the Ca2+-mediated chloride secretion pathway, which requires a separate K+ channel activity from that of CAMP. Pirl1, another small molecule structurally unrelated to secramine B that also inhibits Cdc42 activation in vitro, similarly inhibited cAMP-dependent but not Ca2+-dependent chloride secretion. These results suggest that Rho GTPases may be involved in the regulation of the chloride secretory response and identify secramine B an inhibitor of cAMP-dependent K+ conductance in intestinal epithelial cells. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Harvard Univ, CBR Inst Biomed Res, Boston, MA USA. Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA USA. Childrens Hosp Boston, GI Cell Biol, Div Pediat Gastroenterol & Nutr, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. RP Lencer, WI (reprint author), Childrens Hosp, Div Gastroenterol & Nutr, Enders 720,300 Longwood Ave, Boston, MA 02115 USA. EM wayne.lencer@childrens.harvard.edu FU NIDDK NIH HHS [DK34854, R01 DK048106, P30 DK034854, DK48106, R01 DK084424, R37 DK048106]; PHS HHS [5U54 A1057159] NR 30 TC 7 Z9 7 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 14 PY 2006 VL 71 IS 12 BP 1720 EP 1726 DI 10.1016/j.bcp.2006.03.011 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 049ZH UT WOS:000238056200007 PM 16677615 ER PT J AU Nathan, DG Schechter, AN AF Nathan, DG Schechter, AN TI NIH support for basic and clinical research - Biomedical researcher angst in 2006 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID RESEARCH ENTERPRISE; BUDGET C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Nathan, DG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Room D1644, Boston, MA 02115 USA. EM aschecht@helix.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 NR 17 TC 15 Z9 15 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 JUN 14 PY 2006 VL 295 IS 22 BP 2656 EP 2658 DI 10.1001/jama.295.22.2656 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 052HI UT WOS:000238224000029 PM 16772630 ER PT J AU Nozari, A Safar, P Stezoski, SW Wu, XR Kostelnik, S Radovsky, A Tisherman, S Kochanek, PM AF Nozari, A Safar, P Stezoski, SW Wu, XR Kostelnik, S Radovsky, A Tisherman, S Kochanek, PM TI Critical time window for intra-arrest cooling with cold saline flush in a dog model of cardiopulmonary resuscitation SO CIRCULATION LA English DT Article DE cardiopulmonary resuscitation; cooling; heart arrest; hypothermia; resuscitation ID PROLONGED CARDIAC-ARREST; MILD HYPOTHERMIA; VENTRICULAR-FIBRILLATION; THERAPEUTIC HYPOTHERMIA; CEREBRAL RESUSCITATION; PROFOUND HYPOTHERMIA; COMATOSE SURVIVORS; BLOOD-FLOW; BYPASS; DEFIBRILLATION AB Background - Mild hypothermia improves outcome when induced after cardiac arrest in humans. Recent studies in both dogs and mice suggest that induction of mild hypothermia during cardiopulmonary resuscitation ( CPR) greatly enhances its efficacy. In this study, we evaluate the time window for the beneficial effect of intra-arrest cooling in the setting of prolonged CPR in a clinically relevant large-animal model. Methods and Results - Seventeen dogs had ventricular fibrillation cardiac arrest no flow of 3 minutes, followed by 7 minutes of CPR basic life support and 50 minutes of advanced life support. In the early hypothermia group ( n = 9), mild hypothermia ( 34 degrees C) was induced with an intravenous fluid bolus flush and venovenous blood shunt cooling after 10 minutes of ventricular fibrillation. In the delayed hypothermia group ( n = 8), hypothermia was induced at ventricular fibrillation 20 minutes. After 60 minutes of ventricular fibrillation, restoration of spontaneous circulation was achieved with cardiopulmonary bypass for 4 hours, and intensive care was given for 96 hours. In the early hypothermia group, 7 of 9 dogs survived to 96 hours, 5 with good neurological outcome. In contrast, 7 of 8 dogs in the delayed hypothermia group died within 37 hours with multiple organ failure ( P = 0.012). Conclusions - Early application of mild hypothermia with cold saline during prolonged CPR enables intact survival. Delay in the induction of mild hypothermia in this setting markedly reduces its efficacy. Our data suggest that if mild hypothermia is used during CPR, it should be applied as early as possible. C1 WIL Res Labs, Ashland, OH USA. Univ Pittsburgh, Safer Ctr Resuscitat Res, Pittsburgh, PA USA. Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA. RP Nozari, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM anozari@partners.org OI Kochanek, Patrick/0000-0002-2627-913X NR 33 TC 113 Z9 127 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 13 PY 2006 VL 113 IS 23 BP 2690 EP 2696 DI 10.1161/CIRCULATIONHA.106.613349 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 052HG UT WOS:000238223400006 PM 16769925 ER PT J AU Badjatia, N Bodock, M Rordorf, GA AF Badjatia, N Bodock, M Rordorf, GA TI Rapid infusion of cold saline (4 degrees C) as adjunctive treatment of fever in patients with brain injury SO NEUROLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; CLINICAL-TRIAL; HYPOTHERMIA; SYSTEM; FLUID AB The use of rapid infusion of large-volume cold saline ( CS) as an adjunctive therapy for treating refractory fever in nine patients is reported. A decline in temperature (39.2 +/- 0.3 vs 37.1 +/- 1.2 degrees C, p = 0.006) at 2 hours and fever burden (97.3 +/- 343.8 vs 734.3 +/- 422.3 degrees C* min, p = 0.02) at 12 hours was noted after CS bolus. Rapid infusion of large-volume CS may be used as an adjunct for inducing normothermia in refractory febrile patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurobiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pharm, Boston, MA USA. RP Badjatia, N (reprint author), Columbia Univ Coll Phys & Surg, Div Stroke & Crit Care, Neurol Inst, 710 W 168th St,Box 29, New York, NY 10032 USA. EM nbadjatia@neuro.columbia.edu NR 10 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 13 PY 2006 VL 66 IS 11 BP 1739 EP 1741 DI 10.1212/01.wnl.0000218166.54150.0a PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 052HF UT WOS:000238223300027 PM 16769952 ER PT J AU Walkley, CR Orkin, SH AF Walkley, CR Orkin, SH TI Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE retinoblastoma; conditional mutation; bone marrow transplantation ID TERM REPOPULATING ACTIVITY; ACUTE MYELOID-LEUKEMIA; CYCLE; GENE; MICE; ERYTHROPOIESIS; P27(KIP1); MUTATION; STRESS; CANCER AB Stem cells have been identified as essential for maintaining multiple organ systems, including the hematopoietic system. The distinct cell fates of self-renewal and differentiation of hematopoietic stem cells (HSCs) depend on cell division. Recently, several negative regulators of the cell cycle, such as the cyclin-dependent kinase inhibitors p21(Cip1), P27(Kip1), and P16(INK4a)/p(19ARF), have been demonstrated to have a role in regulating HSC fate decisions, suggesting that regulation of the G(1)-S phase transition can contribute to HSC self-renewal. Because the retinoblastoma protein, Rb, plays a central role in the regulation of the G(1)-S phase cell cycle, we sought to determine whether it has an intrinsic role in the regulation of HSC fate. Surprisingly, we found that HSC function was essentially normal in the absence of Rb. Rb,11,1 HSCs contributed normally to both myeloid and lymphoid lineages in both primary and secondary recipients, and no evidence of transformation was observed. Additionally, we observed a mild myeloid expansion and decrease in mature B cells within the Rb Delta/Delta bone marrow but a similar contribution to phenotypic HSC populations compared with non-deleted bone marrow. The Rb family members p107 and p130 were not deregulated in cells in which Rb had been deleted, as determined by quantitative RT-PCR on the highly enriched stem and primitive progenitor cell lin(-)c-Kit(+)Sca-1(+) population. These studies demonstrate that Rb is not intrinsically required for self-renewal and multilineage differentiation of adult HSCs. C1 Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pediat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pediat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu NR 36 TC 46 Z9 47 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 JUN 13 PY 2006 VL 103 IS 24 BP 9057 EP 9062 DI 10.1093/pnas.0603389103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100030 PM 16754850 ER PT J AU Jinushi, M Hodi, FS Dranoff, G AF Jinushi, M Hodi, FS Dranoff, G TI Therapy-induced antibodies to MHC class I chain-related protein A antagonize immune suppression and stimulate antitumor cytotoxicity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NKG2D; cytotoxic T lymphocyte-associated antigen 4; granulocyte-macrophage colony-stimulating factor; antibody ID MEDIATED TUMOR DESTRUCTION; NKG2D RECEPTOR; T-CELLS; DOWN-REGULATION; MIC LIGANDS; NK CELLS; EXPRESSION; ACTIVATION; CANCER; VIVO AB The activation of NKG2D on innate and adaptive cytotoxic lymphocytes contributes to immune-mediated tumor destruction. Nonetheless, tumor cell shedding of NKG2D ligands, such as MHC class I chain-related protein A (MICA), results in immune suppression through down-regulation of NKG2D surface expression. Here we show that some patients who respond to anti body-blockade of cytotoxic T lymphocyte-associated antigen 4 or vaccination with lethally irradiated, autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor generate high titer antibodies against MICA. These humoral reactions are associated with a reduction of circulating soluble MICA (sMICA) and an augmentation of natural killer (NK) cell and CD8(+) T lymphocyte cytotoxicity. The immunotherapy-induced anti-MICA antibodies efficiently opsonize cancer cells for dendritic cell cross-presentation, which is correlated with a diversification of tumor antigen recognition. The anti-MICA antibodies also accomplish tumor cell lysis through complement fixation. Together, these findings establish a key role for the NKG2D pathway in the clinical activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade and granulocyte-macrophage colony-stimulating factor secreting tumor cell vaccines. Moreover, these results highlight the therapeutic potential of anti-MICA antibodies to overcome immune suppression and effectuate tumor destruction in patients. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Dana 520C,44 Binney St, Boston, MA 02115 USA. EM glenn_dranoff@dfci.harvard.edu RI Jinushi, Masahisa/A-4311-2012 FU NCI NIH HHS [P01 CA078378, CA092625, CA111506, CA66996, CA78378, P01 CA066996, P01 CA092625, R01 CA111506] NR 28 TC 101 Z9 103 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 13 PY 2006 VL 103 IS 24 BP 9190 EP 9195 DI 10.1073/pnas.0603503103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100053 PM 16754847 ER PT J AU Azam, M Nardi, V Shakespeare, WC Metcalf, CA Bohacek, RS Wang, YH Sundaramoorthi, R Sliz, P Veach, DR Bornmann, WG Clarkson, B Dalgarno, DC Sawyer, TK Daley, GQ AF Azam, Mohammad Nardi, Valentina Shakespeare, William C. Metcalf, Chester A., III Bohacek, Regine S. Wang, Yihan Sundaramoorthi, Raji Sliz, Piotr Veach, Darren R. Bornmann, William G. Clarkson, Bayard Dalgarno, David C. Sawyer, Tomi K. Daley, George Q. TI Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE kinase inhibitors; imatinib; combination chemotherapy; chronic myelogenous leukemia ID CHRONIC MYELOID-LEUKEMIA; MUTANT BCR-ABL; TYROSINE KINASE; C-ABL; BLAST CRISIS; CLINICAL RESISTANCE; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; WILD-TYPE; IMATINIB AB Mutation in the ABL kinase domain is the principal mechanism of imatinib resistance in patients with chronic myelogenous leukemia. Many mutations favor active kinase conformations that preclude imatinib binding. Because the active forms of ABL and SRC resemble one another, we tested two dual SRC-ABL kinase inhibitors, AP23464 and PD166326, against 58 imatinib-resistant (IMR) BCR/ABL kinase variants. Both compounds potently inhibit most IMR variants, and in vitro drug selection demonstrates that active (AP23464) and open (PD166326) conformation-specific compounds are less susceptible to resistance than imatinib. Combinations of inhibitors suppressed essentially all resistance mutations, with the notable exception of T3151. Guided by mutagenesis studies and molecular modeling, we designed a series of AP23464 analogues to target T3151. The analogue AP23846 inhibited both native and T3151 variants of BCR/ABL with submicromolar potency but showed nonspecific cellular toxicity. Our data illustrate how conformational dynamics of the ABL kinase accounts for the activity of dual SRC-ABL inhibitors against IMR-mutants and provides a rationale for combining conformation specific inhibitors to suppress resistance. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Brigham & Womens Hosp, Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Ariad Pharmaceut Inc, Cambridge, MA 02139 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77054 USA. RP Daley, GQ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu OI Sliz, Piotr/0000-0002-6522-0835 FU NCI NIH HHS [P01 CA064593, P30 CA008748] NR 40 TC 86 Z9 89 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 13 PY 2006 VL 103 IS 24 BP 9244 EP 9249 DI 10.1073/pnas.0600001103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100062 PM 16754879 ER PT J AU Klinakis, A Szaboics, M Politi, K Kiaris, H Artavanis-Tsakonas, S Efstratiadis, A AF Klinakis, A Szaboics, M Politi, K Kiaris, H Artavanis-Tsakonas, S Efstratiadis, A TI Myc is a Notch1 transcriptional target and a requisite for Notch1-induced mammary tumorigenesis in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE breast cancer; mouse model ID TRANSGENIC MICE; EPITHELIAL-CELLS; C-MYC; BREAST-CANCER; MOUSE MODEL; GENE; EXPRESSION; ONCOGENE; TUMORS; ADENOCARCINOMAS AB To explore the potential involvement of aberrant Notch1 signaling in breast cancer pathogenesis, we have used a transgenic mouse model. In these animals, mouse mammary tumor virus LTR-driven expression of the constitutively active intracellular domain of the Notch1 receptor (N1(1c)) causes development of lactation-dependent mammary tumors that regress upon gland involution but progress to nonregressing, invasive adenocarcinomas in subsequent pregnancies. Up-regulation of Myc in these tumors prompted a genetic investigation of a potential Notch1/Myc functional relationship in breast carcinogenesis. Conditional ablation of Mycin the mammary epithelium prevented the induction of regressing N1(1c) neoplasms and also reduced the incidence of nonregressing carcinomas, which developed with significantly increased latency. Molecular analyses revealed that both the mouse and human Myc genes are direct transcriptional targets of N1(1c) acting through its downstream Cbf1 transcriptional effector. Consistent with this mechanistic link, Notch1 and Myc expression is positively correlated by immuno-staining in 38% of examined human breast carcinomas. C1 Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Cell Biol,Ctr Canc Res, Charlestown, MA 02129 USA. RP Efstratiadis, A (reprint author), Columbia Univ, Dept Genet & Dev, Berrie Med Sci Pavill,1150 St Nicholas Ave, New York, NY 10032 USA. EM ae4@columbia.edu OI Kiaris, Hippokratis/0000-0002-8999-8289 FU NCI NIH HHS [1P01 CA97403, P01 CA097403] NR 33 TC 125 Z9 126 U1 1 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 JUN 13 PY 2006 VL 103 IS 24 BP 9262 EP 9267 DI 10.1073/pnas.0603371103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100065 PM 16751266 ER PT J AU Walter, LC Lindquist, K O'Hare, AM Johansen, KL AF Walter, LC Lindquist, K O'Hare, AM Johansen, KL TI Targeting screening mammography according to life expectancy among women undergoing dialysis SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID STAGE RENAL-DISEASE; MEDICARE CLAIMS DATA; BREAST-CANCER; OLDER WOMEN; SURVIVAL; POPULATION; PROSTATE; CHOICE; RATES; CARE AB Background: Screening guidelines recommend that mammography be targeted to women likely to live longer than 5 years. Because women undergoing dialysis have a reduced but variable life expectancy, their appropriate use of screening is controversial. Therefore, we conducted this study to describe national mammography rates among women undergoing dialysis with differing prognostic factors and to determine whether screening is targeted to healthier women who live longer. Methods: Using the US Renal Data System, we identified 17 090 women aged 50 years or older who started dialysis in 1997. We tracked women for 5 years to ascertain their use of screening mammography or death. Results: The 5-year survival rate was 25%. The biennial screening mammography rate was 25%, ranging from 12% for women aged 80 years or older to 69% for women who were ever on the transplant list. Women who were screened in the past year had a lower death rate than those who were not ( hazards ratio, 0.55; 95% confidence interval, 0.51-0.59). Yet, 2198 women (13%) who died within 5 years underwent screening, and 2004 women (12%) who lived more than 5 years while receiving dialysis did not undergo screening. Conclusions: Screening mammography rates are appropriately low among women undergoing dialysis because the 5-year survival rate is low. Screening is being targeted to women who are healthier and live longer. However, targeting could be improved by increasing screening in the few women undergoing dialysis with substantial life expectancies while decreasing screening in most women undergoing dialysis who live less than 5 years. C1 San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Walter, LC (reprint author), San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,Mailcode 181G, San Francisco, CA 94121 USA. EM Louise.Walter@ucsf.edu FU NIDDK NIH HHS [DK-56182] NR 38 TC 12 Z9 12 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 JUN 12 PY 2006 VL 166 IS 11 BP 1203 EP 1208 DI 10.1001/archinte.166.11.1203 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 051YS UT WOS:000238198200008 PM 16772248 ER PT J AU Dolan, SE Frontera, W Librizzi, J Ljungquist, K Juan, S Dorman, R Cole, ME Kanter, JR Grinspoon, S AF Dolan, SE Frontera, W Librizzi, J Ljungquist, K Juan, S Dorman, R Cole, ME Kanter, JR Grinspoon, S TI Effects of a supervised home-based aerobic and progressive resistance training regimen in women infected with human immunodeficiency virus - A randomized trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BODY-COMPOSITION; DISEASE RISK; FAT REDISTRIBUTION; EUGONADAL MEN; EXERCISE; HIV; ADULTS; FITNESS; INDEXES; LIPODYSTROPHY AB Background: Women infected with human immunodeficiency virus (HIV) increasingly demonstrate abnormalities in fat distribution and metabolism; however, the effects of a home-based exercise regimen in this group have not been investigated. Methods: We conducted a 16-week randomized intervention study of a supervised home-based progressive resistance training and aerobic exercise program in 40 HIV-infected women with increased waist-hip ratio and self-reported fat redistribution. Cross-sectional muscle area and muscle attenuation were measured by computed tomography. Cardiorespiratory fitness was determined by calculated maximum oxygen consumption (VO(2)max) and strength by 1-repetition maximum. Results: Cardiorespiratory fitness (VO(2)max) was markedly lower at baseline (median [95% confidence interval], 15.4 [8.3- 25.2] mL(.)kg(-1)(.)min(-1)) than reported values for healthy female subjects (26- 35 mL(.)kg(-1)(.)min(-1)). Subjects randomized to exercise had significant improvement in mean +/- SEM VO2 max (1.5 +/- 0.8 vs -2.5 +/- 1.6 mL(.)kg(-1)(.)min(-1); P <.001) and endurance (1.0 +/- 0.3 vs - 0.6 +/- 0.3 minute; P < .001). Strength increased at the knee extensors, pectoralis, knee flexors, shoulder abductors, ankle plantar flexors, and elbow flexors (all P < .001). Total muscle area (6 +/- 1 vs 2 +/- 1 cm(2); P= .02) and attenuation (2 +/- 1 vs - 1 +/- 1 Hounsfield unit; P = .03) increased in the exercise group. No significant difference was seen in lipid levels, blood pressure, or abdominal visceral fat between the groups, but subjects randomized to exercise reported improved energy and appearance. Conclusions: A 16-week, supervised, home-based exercise regimen improved measures of physical fitness in HIV-infected women. The effects on strength were most significant, but improvements in cardiorespiratory fitness, endurance, and body composition were also seen. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Phys Therapy Dept, Boston, MA 02114 USA. Harvard Univ, Sch Med, Phys Med & Rehabil Dept, Spaulding Rehabil Hosp, Boston, MA 02115 USA. Partners Home Care Inc, Boston, MA USA. RP Dolan, SE (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Longfellow 207,55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01 RR001066, RR-01066]; NIDDK NIH HHS [R01 DK-49302, R01 DK049302, P30 DK040561, P30 DK040561-11] NR 38 TC 70 Z9 72 U1 1 U2 7 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 JUN 12 PY 2006 VL 166 IS 11 BP 1225 EP 1231 DI 10.1001/archinte.166.11.1225 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 051YS UT WOS:000238198200012 PM 16772251 ER PT J AU Aifantis, I Bassing, CH Garbe, AI Sawai, K Alt, FW von Boehmer, H AF Aifantis, I Bassing, CH Garbe, AI Sawai, K Alt, FW von Boehmer, H TI The E delta enhancer controls the generation of CD4(-)CD8(-) alpha beta TCR-expressing T cells that can give rise to different lineages of alpha beta T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ALLELIC EXCLUSION; RECEPTOR GENE; SELECTION; LOCUS; REQUIRES; CHAIN AB It is well established that the pre-T cell receptor for antigen ( TCR) is responsible for efficient expansion and differentiation of thymocytes with productive TCR beta rearrangements. However, Ptcra- as well as Tcra-targeting experiments have suggested that the early expression of Tcra in CD4(-)CD8(-) cells can partially rescue the development of alpha beta CD4(+)CD8(+) cells in Ptcra-deficient mice. In this study, we show that the TCR E delta but not E.. enhancer function is required for the cell surface expression of alpha beta TCR on immature CD4(-)CD8(-) T cell precursors, which play a crucial role in promoting alpha beta T cell development in the absence of pre-TCR. Thus, alpha beta TCR expression by CD4(-)CD8(-) thymocytes not only represents a transgenic artifact but occurs under physiological conditions. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu RI Garbe, Annette/A-4824-2014 FU NCI NIH HHS [R01 CA105129]; NIAID NIH HHS [R01 AI020047, R01 AI020047-25, R01 AI045846, R01 AI20047, R01 AI45846, R01 AI047281, R01 AI47281] NR 27 TC 18 Z9 19 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 12 PY 2006 VL 203 IS 6 BP 1543 EP 1550 DI 10.1084/jem.20051/11 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 052GC UT WOS:000238219600017 PM 16754716 ER PT J AU Ippolito, GC Schelonka, RL Zemlin, M Ivanov, II Kobayashi, R Zemlin, C Gartland, GL Nitschke, L Pelkonen, J Fujihashi, K Rajewsky, K Schroeder, HW AF Ippolito, GC Schelonka, RL Zemlin, M Ivanov, II Kobayashi, R Zemlin, C Gartland, GL Nitschke, L Pelkonen, J Fujihashi, K Rajewsky, K Schroeder, HW TI Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MARGINAL ZONE; V-H; GENE FAMILIES; DIVERSITY; MICE; SELECTION; REPERTOIRE; EXPRESSION; RESPONSES; SEGMENTS AB Tyrosine and glycine constitute 40% of complementarity determining region 3 of the immunoglobulin heavy chain ( CDR-H3), the center of the classic antigen-binding site. To assess the role of D-H RF1-encoded tyrosine and glycine in regulating CDR-H3 content and potentially influencing B cell function, we created mice limited to a single D-H encoding asparagine, histidine, and arginines in RF1. Tyrosine and glycine content in CDR-H3 was halved. Bone marrow and spleen mature B cell and peritoneal cavity B-1 cell numbers were also halved, whereas marginal zone B cell numbers increased. Serum immunoglobulin G subclass levels and antibody titers to T-dependent and T-independent antigens all declined. Thus, violation of the conserved preference for tyrosine and glycine in D-H RF1 alters CDR-H3 content and impairs B cell development and antibody production. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat Dent, Birmingham, AL 35294 USA. Univ Alabama, Dept Genet, Birmingham, AL 35294 USA. Univ Erlangen Nurnberg, Dept Genet, D-91058 Erlangen, Germany. Univ Kuopio, Dept Clin Microbiol, Kuopio 70211, Finland. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Schroeder, HW (reprint author), Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. EM hwsj@uab.edu OI Zemlin, Michael/0000-0001-9528-7419 FU FIC NIH HHS [F06 TW002130, TW02130]; NIAID NIH HHS [AI07051, R01 AI048115, R01 AI047322, R56 AI048115, AI42732, T32 AI007051, AI48115]; NICHD NIH HHS [HD043327, K08 HD043327] NR 49 TC 58 Z9 58 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 12 PY 2006 VL 203 IS 6 BP 1567 EP 1578 DI 10.1084/jem.20052217 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 052GC UT WOS:000238219600019 PM 16754718 ER PT J AU Garbe, AI Krueger, A Gounari, F Zuniga-Pflucker, JC von Boehmer, H AF Garbe, AI Krueger, A Gounari, F Zuniga-Pflucker, JC von Boehmer, H TI Differential synergy of Notch and T cell receptor signaling determines alpha beta versus gamma delta lineage fate SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PRE-TCR; LYMPHOCYTE DEVELOPMENT; BETA/GAMMA-DELTA; IN-VITRO; PT-ALPHA; EXPRESSION; SELECTION; GENE; THYMOCYTES; REPERTOIRE AB Thymic precursors expressing the pre-T cell receptor ( TCR), the gamma delta TCR, or the alpha beta TCR can all enter the CD(4+)8(+) alpha beta lineage, albeit with different efficacy. Here it is shown that proliferation and differentiation of precursors with the different TCRs into alpha beta lineage cells require Notch signaling at the DN3 stage of thymic development. At the DN4 stage, Notch signaling still significantly contributes to the generation of alpha beta T cells. In particular, in alpha beta lineage commitment, the pre-TCR synergizes more efficiently with Notch signals than the other two TCRs, whereas gamma delta TCR-expressing cells can survive and expand in the absence of Notch signals, even though Notch signaling enhances their proliferation. These observations suggest a new model of alpha beta versus gamma delta lineage choice in which lineage fate is determined by the extent of synergy between TCR and Notch signaling and in which the evolutionarily recent advent of the cell-autonomously signaling pre-TCR increased the efficacy of alpha beta T cell generation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Tufts New England Med Ctr, Boston, MA 02111 USA. Univ Toronto, Toronto, ON M4N 3M5, Canada. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM Harald_von_Boehmer@dfci.harvard.edu RI Krueger, Andreas/B-9427-2009; Zuniga-Pflucker, Juan/H-1295-2012; Garbe, Annette/A-4824-2014 OI Krueger, Andreas/0000-0001-7873-7334; FU NCI NIH HHS [P01 CA10990]; NIAID NIH HHS [R01 AI047281, R01 AI45846, R01 AI045846, R01 AI47281] NR 47 TC 69 Z9 69 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 12 PY 2006 VL 203 IS 6 BP 1579 EP 1590 DI 10.1084/jem.20060474 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 052GC UT WOS:000238219600020 PM 16754723 ER PT J AU Wong, SJ Machtay, M Li, Y AF Wong, SJ Machtay, M Li, Y TI Locally recurrent, previously irradiated head and neck cancer: Concurrent re-irradiation and chemotherapy, or chemotherapy alone? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID SQUAMOUS-CELL CARCINOMA; COOPERATIVE-ONCOLOGY-GROUP; CISPLATIN PLUS FLUOROURACIL; CONCOMITANT CHEMOTHERAPY; OROPHARYNX CARCINOMA; DOSE REIRRADIATION; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; SALVAGE SURGERY; CAROTID-ARTERY AB Patients with locally recurrent head and neck cancer previously treated with radiation have a poor prognosis. Administration of a second course of radiation to tissues within a previous radiation portal, has been traditionally considered unsafe. Survival rates of highly selected patients treated with concurrent chemotherapy and re-irradiation may be as high as 25% at 2 years-exceeding the outcome of matched historical controls treated with chemotherapy alone (10%). However, many questions exist regarding the use of re-irradiation. Uncertainty exists over the criteria for selecting patients who are most appropriate for treatment with re-irradiation. Even greater concern exists regarding toxicity and functional sequelae associated with the use of re-irradiation. Whether the benefits of re-irradiation on locoregional disease control and survival outweigh its potentially severe and life-threatening adverse effects is not clear. In this review, we will discuss re-irradiation and other treatment options for squamous cell carcinoma patients with previously irradiated, locoregional recurrent or second primary tumors in the head and neck, and describe a recently initiated randomized trial comparing chemotherapy plus re-irradiation with chemotherapy. C1 Med Coll Wisconsin, Dept Med, Div Neoplast Dis, Milwaukee, WI 53226 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Bodine Canc Ctr, Philadelphia, PA 19107 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wong, SJ (reprint author), Med Coll Wisconsin, Dept Med, Div Neoplast Dis, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM swong@mcw.edu NR 43 TC 65 Z9 69 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 JUN 10 PY 2006 VL 24 IS 17 BP 2653 EP 2658 DI 10.1200/JCO.2005.05.3850 PG 6 WC Oncology SC Oncology GA 054MB UT WOS:000238379900009 PM 16763279 ER PT J AU Roy, K Wang, LL Makrigiorgos, GM Price, BD AF Roy, K Wang, LL Makrigiorgos, GM Price, BD TI Methylation of the ATM promoter in glioma cells alters ionizing radiation sensitivity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE glioblastoma; radiation therapy; ionizing radiation; ATM; methylation; radiiosensitivity ID CENTRAL-NERVOUS-SYSTEM; ATAXIA-TELANGIECTASIA; BREAST-CANCER; DNA-DAMAGE; MUTATIONS; GENE; EXPRESSION; RADIOSENSITIVITY; TUMORS; HYPERMETHYLATION AB Glioblastomas are among the malignancies most resistant to radiation therapy. In contrast, cells lacking the ATM protein are highly sensitive to ionizing radiation. The relationship between ATM protein expression and radiosensitivity in 3 glioma cell lines was examined. T98G cells exhibited normal levels of ATM protein, whereas U118 and U87 cells had significantly lower levels of ATM and increased (> 2-fold) sensitivity to ionizing radiation compared to T98G cells. The ATM promoter was methylated in U87 cells. Demethylation by azacytidine treatment increased ATM protein levels in the U87 cells and decreased their radiosensitivity. In contrast, the ATM promoter in U I IS cells was not methylated. Further, expression of exogenous ATM did not significantly alter the radiosensitivity of U118 cells. ATM expression is therefore heterogeneous in the glioma cells examined. In conclusion, methylation of the ATM promoter may account for the variable radiosensitivity and heterogeneous ATM expression in a fraction of glioma cells. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genom Stabil & DNA Repair,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM brendan_price@dfci.harvard.edu FU NCI NIH HHS [CA64585, CA93602, R01 CA064585] NR 34 TC 34 Z9 34 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 JUN 9 PY 2006 VL 344 IS 3 BP 821 EP 826 DI 10.1016/j.bbrc.2006.03.222 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 043FI UT WOS:000237585000018 PM 16631604 ER PT J AU Marracci, GH Marquardt, WE Strehlow, A McKeon, GP Gross, J Buck, DC Kozell, LB Bourdette, DN AF Marracci, GH Marquardt, WE Strehlow, A McKeon, GP Gross, J Buck, DC Kozell, LB Bourdette, DN TI Lipoic acid downmodulates CD4 from human T lymphocytes by dissociation of p56(Lck) SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE CD4; p56(Lck); lipoic acid ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; VIRUS TYPE-1 NEF; MULTIPLE-SCLEROSIS; SERINE PHOSPHORYLATION; RAPID INTERNALIZATION; CD4-P56(LCK) COMPLEX; OXIDATIVE STRESS; CYTOPLASMIC TAIL; CELL-ACTIVATION AB Lipoic acid is an antioxidant that suppresses and treats a model of multiple sclerosis, experimental autoimmune encephalomyelitis. We now demonstrate that treatment of human PBMC and T cell lines with LA downmodulated CD4 expression in a concentration-dependent manner. LA treatment of Con A stimulated PBMC specifically removed CD4 from the T-cell surface, but not CD3. Epitope masking by LA was excluded by using monoclonal antibodies targeting different domains of CD4. Incubation on ice inhibited CD4 removal following LA treatment, suggesting that endocytosis was involved in its downmodulation. LA is in a unique category of compounds that induce CD4 downmodulation by various mechanisms (e.g., gangliosides). We hypothesized that LA might induce dissociation of p56(Lek) from CD4. thus leading to its downmodulation. Immunoblot analyses demonstrated reduced co-precipitation of p56(Lck) from Jurkat T-cells following LA treatment and precipitation of CD4. This unique immunomodulatory effect of LA warrants further investigation. Published by Elsevier Inc. C1 Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. RP Marracci, GH (reprint author), Portland Vet Affairs Med Ctr, R&D 65,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM marracci@ohsu.edu OI Kozell, Laura/0000-0003-3059-2046 FU NCCIH NIH HHS [P50 AT00066-01] NR 49 TC 9 Z9 9 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 9 PY 2006 VL 344 IS 3 BP 963 EP 971 DI 10.1016/j.bbrc.2006.03.172 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 043FI UT WOS:000237585000038 PM 16631599 ER PT J AU Jiang, XF Sun, YL Chen, SJ Roy, K Price, BD AF Jiang, XF Sun, YL Chen, SJ Roy, K Price, BD TI The FATC domains of PIKK proteins are functionally equivalent and participate in the Tip60-dependent activation of DNA-PKcs and ATM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KINASE CATALYTIC SUBUNIT; HISTONE ACETYLTRANSFERASE COMPLEX; DOUBLE-STRAND BREAKS; IONIZING-RADIATION; IN-VITRO; AUTOPHOSPHORYLATION; DAMAGE; PHOSPHORYLATION; CHROMATIN; SITES AB Members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, including the ATM, DNA-PKcs, Atr, and Trrap proteins, function in signal transduction pathways that activate the DNA damage response. PIKK proteins contain a conserved C-terminal FAT/kinase domain/FATC domain structure. The FATC domain of ATM mediates the interaction between ATM and Tip60, a histone acetyltransferase that regulates activation of ATM. Here, we examined whether the FATC domains of DNA-PKcs, Atr, and Trrap were also able to interact with Tip60. Deletion of the FATC domain of ATM blocked the interaction between ATM and Tip60 and suppressed the activation of ATM kinase activity by DNA damage. Replacement of the FATC domain of ATM with the FATC domains of DNA-PKcs, Atr, or Trrap restored the activation of ATM and its association with Tip60. These results indicate that the FATC domains of DNA-PKcs, Atr, Trrap, and ATM are functionally equivalent. Immunoprecipitation experiments demonstrated that Tip60 is constitutively associated with DNA-PKcs and that the histone acetyltransferase activity associated with DNA-PKcs is up-regulated by DNA damage. When Tip60 expression was suppressed by small interfering RNA, the activation of DNA-PKcs ( measured by autophosphorylation of DNA-PKcs at serine 2056 and threonine 2609) was inhibited, demonstrating a key role for Tip60 in the activation of DNA-PKcs by DNA damage. The conserved FATC domain of PIKK proteins may therefore function as a binding domain for the Tip60 histone acetyltransferase. Further, the ability of Tip60 to regulate the activation of both ATM and DNA-PKcs in response to DNA damage demonstrates that Tip60 is a key component of the DNA damage-signaling network. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Gen Stabil & DNA Repair, Boston, MA 02115 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Gen Stabil & DNA Repair, 44 Binney St,JF5 16, Boston, MA 02115 USA. EM brendan_price@dfci.harvard.edu FU NCI NIH HHS [R01 CA064585] NR 41 TC 77 Z9 81 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 9 PY 2006 VL 281 IS 23 BP 15741 EP 15746 DI 10.1074/jbc.M513172200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 049DM UT WOS:000237996000021 PM 16603769 ER PT J AU Quackenbush, J AF Quackenbush, John TI Current concepts - Microarray analysis and tumor classification SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID GENE-EXPRESSION PATTERNS; DNA MICROARRAY; CDNA MICROARRAY; BREAST-CANCER; OLIGONUCLEOTIDE ARRAYS; ALZHEIMERS-DISEASE; MUSCLE-CELLS; PLATFORMS; PROFILES; PREDICTION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Quackenbush, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM johnq@jimmy.harvard.edu NR 61 TC 266 Z9 283 U1 7 U2 16 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 JUN 8 PY 2006 VL 354 IS 23 BP 2463 EP 2472 DI 10.1056/NEJMra042342 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 050PQ UT WOS:000238100800008 PM 16760446 ER PT J AU Kagan, A Hochberg, EP Gilman, MD Hasserjian, RP AF Kagan, A Hochberg, EP Gilman, MD Hasserjian, RP TI A man with cavitary lung lesions - Lymphomatoid granulomatosis, with progression from grade 1 to grade 3 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ANGIOCENTRIC IMMUNOPROLIFERATIVE LESIONS; LYMPHOPROLIFERATIVE DISEASE; SENSORINEURAL DEAFNESS; RITUXIMAB MONOTHERAPY; B-LYMPHOCYTES; PNEUMONIA; IMMUNODEFICIENCY; INFECTION; FEATURES; GENOMES C1 Massachusetts Gen Hosp, Dept Med, Div 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 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 Kagan, A (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. NR 34 TC 5 Z9 6 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 8 PY 2006 VL 354 IS 23 BP 2485 EP 2493 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 050PQ UT WOS:000238100800012 ER PT J AU Harris, NL Horning, SJ AF Harris, NL Horning, SJ TI Burkitt's lymphoma - The message from microarrays SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CELL LYMPHOMAS; ONCOLOGY-GROUP; FEATURES C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Stanford Med Sch, Dept Med, Div Oncol, Stanford, CA USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 15 TC 28 Z9 30 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 JUN 8 PY 2006 VL 354 IS 23 BP 2495 EP 2498 DI 10.1056/NEJMe068075 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 050PQ UT WOS:000238100800013 PM 16760450 ER PT J AU Gudi, R Barkinge, J Hawkins, S Chu, F Manicassamy, S Sun, Z Duke-Cohan, JS Prasad, KVS AF Gudi, R Barkinge, J Hawkins, S Chu, F Manicassamy, S Sun, Z Duke-Cohan, JS Prasad, KVS TI Siva-1 negatively regulates NF-kappa B activity: effect on T-cell receptor-mediated activation-induced cell death (AICD) SO ONCOGENE LA English DT Article DE TCR; apoptosis; NF-kappa B; Bcl-xL; c-FLIP; AICD ID RADIATION-INDUCED APOPTOSIS; PROAPOPTOTIC PROTEIN; EXPRESSION; INTERACTS; PATHWAY; BINDING; FAMILY; MEMBER; CD27 AB Ligation of TCRs on stimulated T cells leads to activation-induced cell death (AICD) resulting in the downregulation of immune responses, a process essential for T-cell homeostasis. In this study, using transformed T-cell lines such as Jurkat and Do11.10 as cellular models of TCR-mediated AICD, we have demonstrated that the proapoptotic protein Siva-1 is required for TCR-induced apoptosis. Knockdown of Siva-1 rendered T cells specifically resistant to anti-CD3 but not Fas-induced apoptosis. Further, we observed that in Siva-1 knockout Jurkat cells, TCR-mediated activation of the canonical and non-canonical limbs of the NF-kappa B pathway are significantly enhanced as reflected by elevated nuclear levels of p65 and RelB, respectively. In addition, loss of endogenous Siva-1 also resulted in the enhanced expression of NF-kappa B-responsive anti-apoptotic genes such as Bcl-xL and c-FLIP. Interestingly, the c-FLIPshort was detected only in TCR-ligated Siva-1 knockdown Jurkat cells. These results demonstrate a significant role for endogenous Siva-1, through its inhibitory effect on NF-kappa B activity, in TCR-mediated AICD with implications in peripheral tolerance, T-cell homeostasis and cancer. C1 Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60612 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Prasad, KVS (reprint author), Univ Illinois, Dept Microbiol & Immunol, 835 S Wolcott Ave,Room 820, Chicago, IL 60612 USA. EM kanteti@uic.edu OI Duke-Cohan, Jonathan/0000-0002-9478-9609 NR 20 TC 28 Z9 31 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 JUN 8 PY 2006 VL 25 IS 24 BP 3458 EP 3462 DI 10.1038/sj.onc.1209381 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 055KB UT WOS:000238448100010 PM 16491128 ER PT J AU Motzer, RJ Rini, BI Bukowski, RM Curti, BD George, DJ Hudes, GR Redman, BG Margolin, KA Merchan, JR Wilding, G Ginsberg, MS Bacik, J Kim, ST Baum, CM Michaelson, MD AF Motzer, RJ Rini, BI Bukowski, RM Curti, BD George, DJ Hudes, GR Redman, BG Margolin, KA Merchan, JR Wilding, G Ginsberg, MS Bacik, J Kim, ST Baum, CM Michaelson, MD TI Sunitinib in patients with metastatic renal cell carcinoma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID TYROSINE KINASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; FACTOR RECEPTOR; ANTITUMOR-ACTIVITY; RANDOMIZED-TRIAL; LUNG-CANCER; IN-VIVO; SU11248; INTERLEUKIN-2; INTERFERON AB Context Current treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients. Objective To confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy. Design, Setting, and Patients Open-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N=106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy. Intervention Repeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle. Main Outcome Measures Assessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate ( complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians ( investigator assessment). Results All 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months ( 95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively. Conclusion The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC. C1 Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, New York, NY 10021 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Cleveland Clin Fdn, Expt Therapeut Program, Cleveland, OH 44195 USA. Robert W Franz Canc Ctr, Earle A Chiles Res Inst, Portland, OR USA. Duke Univ, Med Ctr, Dept Med, Div Med Oncol, Durham, NC 27710 USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. City Hope Natl Med Ctr, Div Med Oncol, Duarte, CA 91010 USA. Mayo Clin, Dept Oncol, Rochester, MN USA. Univ Wisconsin, Ctr Comprehens Canc, Dept Med, Madison, WI USA. Pfizer Inc, Oncol Clin Dev, La Jolla, CA USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Motzer, RJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. EM motzerr@mskcc.org NR 24 TC 812 Z9 853 U1 4 U2 29 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 JUN 7 PY 2006 VL 295 IS 21 BP 2516 EP 2524 DI 10.1001/jama.295.21.2516 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 049ZQ UT WOS:000238057300027 PM 16757724 ER PT J AU Oliver, D Taberner, AM Thurm, H Sausbier, M Arntz, C Ruth, P Fakler, B Liberman, MC AF Oliver, D Taberner, AM Thurm, H Sausbier, M Arntz, C Ruth, P Fakler, B Liberman, MC TI The role of BKCa channels in electrical signal encoding in the mammalian auditory periphery SO JOURNAL OF NEUROSCIENCE LA English DT Article DE calcium-activated potassium channel; Maxi-K; inner ear; hearing; frequency tuning; adaptation ID INNER HAIR-CELLS; RETINAL AMACRINE CELLS; GUINEA-PIG COCHLEA; K+ CHANNELS; NERVE FIBERS; POTASSIUM CURRENTS; AFFERENT SYNAPSE; MOUSE COCHLEA; ADAPTATION; CALCIUM AB Large-conductance voltage- and Ca2+- activated K+ channels (BKCa) are involved in shaping spiking patterns in many neurons. Less is known about their role in mammalian inner hair cells (IHCs), mechanosensory cells with unusually large BKCa currents. These currents may be involved in shaping the receptor potential, implying crucial importance for the properties of afferent auditory signals. We addressed the function of BKCa by recording sound-induced responses of afferent auditory nerve ( AN) fibers from mice with a targeted deletion of the pore-forming alpha-subunit of BKCa (BK alpha(-/-)) and comparing these with voltage responses of current-clamped IHCs. BKCa-mediated currents in IHCs were selectively abolished in BK alpha(-/-), whereas cochlear physiology was essentially normal with respect to cochlear sensitivity and frequency tuning. BK alpha(-/-) AN fibers showed deteriorated precision of spike timing, measured as an increased variance of first spike latency in response to tone bursts. This impairment could be explained by a slowed voltage response in the presynaptic IHC resulting from the reduced K+ conductance in the absence of BKCa. Maximum spike rates of AN fibers were reduced nearly twofold in BK alpha(-/-), contrasting with increased voltage responses of IHCs. In addition to presynaptic changes, which may be secondary to a modest depolarization of BK alpha(-/-) IHCs, this reduction in AN rates suggests a role of BKCa in postsynaptic AN neurons, which was supported by increased refractory periods. In summary, our results indicate an essential role of IHC BKCa channels for precise timing of high-frequency cochlear signaling as well as a function of BKCa in the primary afferent neuron. C1 Univ Freiburg, Inst Physiol, D-79104 Freiburg, Germany. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, MIT, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. Univ Tubingen, Dept Pharmacol & Toxicol, D-72074 Tubingen, Germany. RP Oliver, D (reprint author), Univ Freiburg, Inst Physiol, Hermann Herder Str 7, D-79104 Freiburg, Germany. EM dominik.oliver@physiologie.uni-freiburg.de RI Oliver, Dominik/F-5845-2013 FU NIDCD NIH HHS [R01 DC00188, P30 DC005209, R01 DC000188] NR 53 TC 49 Z9 50 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 7 PY 2006 VL 26 IS 23 BP 6181 EP 6189 DI 10.1523/JNEUROSCI.1047-06.2006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 051QC UT WOS:000238174600009 PM 16763026 ER PT J AU Seebeck, FP Szostak, JW AF Seebeck, FP Szostak, JW TI Ribosomal synthesis of dehydroalanine-containing peptides SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ESCHERICHIA-COLI; PROTEIN; ACID; BIOSYNTHESIS; SELENALYSINE; MODE C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Simches Res Ctr, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU NIGMS NIH HHS [F32 GM074505, F32 GM074505-02, GM 074505-02] NR 24 TC 55 Z9 55 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 7 PY 2006 VL 128 IS 22 BP 7150 EP 7151 DI 10.1021/ja060966w PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 048EZ UT WOS:000237931700019 PM 16734454 ER PT J AU Flampouri, S Jiang, SB Sharp, GC Wolfgang, J Patel, AA Choi, NC AF Flampouri, Stella Jiang, Steve B. Sharp, Greg C. Wolfgang, John Patel, Abhijit A. Choi, Noah C. TI Estimation of the delivered patient dose in lung IMRT treatment based on deformable registration of 4D-CT data and Monte Carlo simulations SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; RESPIRATORY MOTION; TUMOR MOTION; IMAGE REGISTRATION; RADIATION-THERAPY; CALCULATION TOOL; TARGET VOLUME; MULTISLICE CT; RADIOTHERAPY; VALIDATION AB The purpose of this study is to accurately estimate the difference between the planned and the delivered dose due to respiratory motion and free breathing helical CT artefacts for lung IMRT treatments, and to estimate the impact of this difference on clinical outcome. Six patients with representative tumour motion, size and position were selected for this retrospective study. For each patient, we had acquired both a free breathing helical CT and a ten-phase 4D-CT scan. A commercial treatment planning system was used to create four IMRT plans for each patient. The first two plans were based on the GTV as contoured on the free breathing helical CT set, with a GTV to PTV expansion of 1.5 cm and 2.0 cm, respectively. The third plan was based on the ITV, a composite volume formed by the union of the CTV volumes contoured on free breathing helical CT, end-of-inhale (EOI) and end-of-exhale (EOE) 4D-CT. The fourth plan was based on GTV contoured on the EOE 4D-CT. The prescribed dose was 60 Gy for all four plans. Fluence maps and beam setup parameters of the IMRT plans were used by the Monte Carlo dose calculation engine MCSIM for absolute dose calculation on both the free breathing CT and 4D-CT data. CT deformable registration between the breathing phases was performed to estimate the motion trajectory for both the tumour and healthy tissue. Then, a composite dose distribution over the whole breathing cycle was calculated as a final estimate of the delivered dose. EUD values were computed on the basis of the composite dose for all four plans. For the patient with the largest motion effect, the difference in the EUD of CTV between the planed and the delivered doses was 33, 11, 1 and 0 Gy for the first, second, third and fourth plan, respectively. The number of breathing phases required for accurate dose prediction was also investigated. With the advent of 4D-CT, deformable registration and Monte Carlo simulations, it is feasible to perform an accurate calculation of the delivered dose, and compare our delivered dose with doses estimated using prior techniques. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Flampouri, S (reprint author), Univ Florida, Coll Med, Florida Proton Therapy Inst, Jacksonville, FL 32206 USA. EM stellaf@ufl.edu NR 35 TC 78 Z9 78 U1 1 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 7 PY 2006 VL 51 IS 11 BP 2763 EP 2779 DI 10.1088/0031-9155/51/11/006 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 062DG UT WOS:000238924200006 PM 16723765 ER PT J AU Paganetti, H AF Paganetti, Harald TI Monte Carlo calculations for absolute dosimetry to determine machine outputs for proton therapy fields SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BRAGG PEAK FIELDS; NUCLEAR-INTERACTIONS; RADIATION-THERAPY; DOSE CALCULATIONS; W-VALUE; BEAM; SIMULATIONS; AIR; ACCELERATOR; ALGORITHM AB The prescribed dose in radiation therapy has to be converted into machine monitor units for patient treatment. This is done routinely for each spread-out Bragg peak (SOBP) field either by calibration measurements, by using analytical algorithms or by relying on empirical data. At the Northeast Proton Therapy Center, a monitor unit corresponds to a fixed amount of charge collected in a segmented transmission ionization chamber inside the treatment head. The goal of this work was to use a detailed Monte Carlo model of the treatment head to calculate the dose delivered to the patient as a function of ionization chamber reading, i.e. to yield absolute dose in patients in terms of machine monitor units. The results show excellent agreement with measurements. For 50 SOBP fields considered in this study, the mean absolute difference between the experimental and the calculated value is 1.5%, where similar to 50% of the fields agree within 1%. This is within the uncertainties of the data. The Monte Carlo method has advantages over analytical algorithms because it takes into account scattered and secondary radiation, does not rely on empirical parameters, and provides a tool to study the influence of parts of the treatment head on the ionization chamber reading. Compared to experimental methods the Monte Carlo method has the advantage of being able to verify the dose in the patient geometry. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [P01 CA021239-27, P01 CA021239, P01 CA21239] NR 25 TC 32 Z9 32 U1 1 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN 7 PY 2006 VL 51 IS 11 BP 2801 EP 2812 DI 10.1088/0031-9155/51/11/008 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 062DG UT WOS:000238924200008 PM 16723767 ER PT J AU Nakazawa, T Takahashi, H Shimura, M AF Nakazawa, Toru Takahashi, Hidetoshi Shimura, Masahiko TI Estrogen has a neuroprotective effect on axotomized RGCs through ERK signal transduction pathway SO BRAIN RESEARCH LA English DT Article DE retinal ganglion cell; signal transduction; mitogen-activated protein kinase; optic nerve axotomy; estrogen; glaucoma ID RETINAL GANGLION-CELLS; ACTIVATED PROTEIN-KINASE; OPEN-ANGLE GLAUCOMA; ISCHEMIA-REPERFUSION INJURY; CENTRAL-NERVOUS-SYSTEM; IN-VIVO; NEUROTROPHIC FACTOR; REGULATED KINASE; GENE-TRANSFER; RAT AB The neuroprotective effects of estrogen on neuronal cells in central nervous system have been described previously, however, the mechanisms of neuroprotective effect of estrogen against retinal ganglion cell (RGC) death has not been well identified. To examine the role of endogenous sex steroids produced in ovary, retina samples were prepared from female rats with or without ovariectomy and the density of RGC was calculated. Ovariectomy alone had no effect on the density of fluorogold (FG)-labeled RGC without injury, while the density of surviving RGC after optic nerve axotomy with ovariectomy was significantly decreased compared to that without ovariectomy. To examine the role of exogenous sex steroids, 17 estradiol was injected into the vitreous cavity in ovariectomized rats and showed neuroprotective effect on axotomy-induced RGC death while exogenous progesterone showed no effect. Immunoblot and immunohistochemical analysis demonstrated that ERK-c-Fos signal transduction pathway was activated by exogenous 17 beta-estradiol in ganglion cell layer. U0126, an ERK inhibitor, inhibited the neuroprotective effect of estrogen on axotomized RGC death. These data suggest that estrogen has neuroprotective effect through activation of ERK-c-Fos signaling pathway on axotomy-induced RGC death. The neuroprotective effect of estrogen may have therapeutic benefits in retinal diseases associated with RGC death such as glaucoma. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Angiogenesis Lab, Boston, MA 02132 USA. Tohoku Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Sendai, Miyagi 9808574, Japan. Tohoku Hosp, NTT E Japan, Dept Ophthalmol, Sendai, Miyagi 9808574, Japan. RP Nakazawa, T (reprint author), Massachusetts Eye & Ear Infirm, Angiogenesis Lab, 3rd Floor,325 Cambridge St, Boston, MA 02114 USA. EM ntoru@fa2.so-net.ne.jp NR 48 TC 22 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 6 PY 2006 VL 1093 BP 141 EP 149 DI 10.1016/j.brainres.2006.03.084 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 064CZ UT WOS:000239068100015 PM 16696958 ER PT J AU Packer, M Abraham, WT Mehra, MR Yancy, CW Lawless, CE Mitchell, JE Smart, FW Bijou, R O'Connor, CM Massie, BM Pina, IL Greenberg, BH Young, JB Fishbein, DP Hauptman, PJ Bourge, RC Strobeck, JE Murali, S Schocken, D Teerlink, JR Levy, WC Trupp, RJ Silver, MA AF Packer, M Abraham, WT Mehra, MR Yancy, CW Lawless, CE Mitchell, JE Smart, FW Bijou, R O'Connor, CM Massie, BM Pina, IL Greenberg, BH Young, JB Fishbein, DP Hauptman, PJ Bourge, RC Strobeck, JE Murali, S Schocken, D Teerlink, JR Levy, WC Trupp, RJ Silver, MA CA PREDICT Study Investigators TI Utility of impedance cardiography for the identification of short-term risk of clinical decompensation in stable patients with chronic heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ELECTRICAL-IMPEDANCE; CARDIAC-OUTPUT; BIOIMPEDANCE; THERMODILUTION; CARDIOMYOPATHY; PRESSURE AB OBJECTIVES This study sought to assess the potential utility of impedance cardiography (ICG) in predicting clinical deterioration in ambulatory patients with heart failure (HF). BACKGROUND Impedance cardiography uses changes in thoracic electrical impedance to estimate hemodynamic variables, but its ability to predict clinical events has not been evaluated. METHODS We prospectively evaluated 212 stable patients with HF and a recent episode of clinical decompensation who underwent serial clinical evaluation and blinded ICG testing every 2 weeks for 26 weeks and were followed up for the occurrence of death or worsening HF requiring hospitalization or emergent care. RESULTS During the study, 59 patients experienced 104 episodes of decompensated HF (16 deaths, 78 hospitalizations, and 10 emergency visits). Multivariate analysis identified 6 clinical and ICG variables that independently predicted an event within 14 days of assessment. These included three clinical variables (visual analog score, New York Heart Association functional class, and systolic blood pressure) and three ICG parameters (velocity index, thoracic fluid content index, and left ventricular ejection time). The three ICG parameters combined into a composite score was a powerful predictor of an event during the next 14 days (p = 0.0002). Visits with a high-risk composite score had 2.5 times greater likelihood and those with a low-risk score had a 70% lower likelihood of a near-term event compared with visits at intermediate risk. CONCLUSIONS These results suggest that when performed at regular intervals in stable patients with HF with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation. C1 Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. Ohio State Univ, Ctr Heart, Columbus, OH 43210 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. DuPage Med Grp, Chicago, IL USA. SUNY, Downstate Med Ctr, New York, NY USA. St Lukes Episcopal Hosp, Texas Heart Inst, Houston, TX 77030 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Duke Univ, Med Ctr, Durham, NC USA. San Francisco Vet Adm Med Ctr, San Francisco, CA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Washington, Seattle, WA 98195 USA. St Louis Univ, St Louis, MO 63103 USA. Univ Alabama, Birmingham, AL USA. Heart Lung Associates Amer, Hawthorne, NJ USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ S Florida, Tampa, FL USA. Advocate Christ Med Ctr, Oak Lawn, IL USA. RP Packer, M (reprint author), Univ Texas, SW Med Ctr, 5323 Harry Hines Blvd,Room E5-506P, Dallas, TX 75390 USA. EM Milton.Packer@UTSouthwestern.edu RI Teerlink, John/D-2986-2012; OI Mehra, Mandeep/0000-0001-8683-7044 NR 26 TC 100 Z9 106 U1 2 U2 5 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 JUN 6 PY 2006 VL 47 IS 11 BP 2245 EP 2252 DI 10.1016/j.jacc.2005.12.071 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 048YC UT WOS:000237981500015 PM 16750691 ER PT J AU Scirica, BM Morrow, DA Cannon, CP Ray, KK Sabatine, MS Jarolim, P Shui, A McCabe, CH Braunwald, E AF Scirica, BM Morrow, DA Cannon, CP Ray, KK Sabatine, MS Jarolim, P Shui, A McCabe, CH Braunwald, E CA PROVE IT-TIMI 22 Investigators TI Intensive statin therapy and the risk of hospitalization for heart failure after an acute coronary syndrome in the PROVE IT-TIMI 22 study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; MYOCARDIAL-INFARCTION; NATRIURETIC PEPTIDE; HYPERTENSIVE PATIENTS; PROGNOSTIC VALUE; ATORVASTATIN; OUTCOMES; INFLAMMATION; SIMVASTATIN; PRAVASTATIN AB OBJECTIVES We aimed to determine whether intensive statin therapy reduces hospitalization for heart failure (HF) in high-risk patients. BACKGROUND While the relationship between intensive statin therapy and ischemic events is well established, its relationship to the risk of HF after an acute coronary syndrome (ACS) is not well defined. METHODS The Pravastatin or Atorvastatin Evaluation and Infection Trial-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TlMI 22) study randomized 4,162 patients, stabilized after ACS, to either intensive statin therapy (atorvastatin 80 mg) or moderate statin therapy (pravastatin 40 mg). Hospitalization for HF occurring more than 30 days after randomization was determined during a mean follow-up of 24 months. B-type natriuretic peptide (BNP) levels were measured at baseline (median seven days after randomization). RESULTS Treatment with atorvastatin 80 mg significantly reduced the rate of hospitalization for HF (1.6% vs. 3.1%, hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.35 to 0.85, p = 0.008) independently of a recurrent myocardial infarction or prior history of HF. The risk of HF increased steadily with increasing quartiles of BNP (HR 2.6, 95% CI 1.2 to 5.5, p = 0.016 for the highest quartile compared with the lowest). Among patients with elevated levels of BNP (> 80 pg/ml), treatment with atorvastatin significantly reduced the risk of HF compared with pravastatin (HR 0.32, 95% CI 0.13 to 0.8, p = 0.014). A meta-analysis of four trials that included 27,546 patients demonstrates a 27% reduction in the odds of hospitalization for HF with intensive statin therapy. CONCLUSIONS Intensive statin therapy reduces the risk of hospitalization for HF after ACS with the most gain inpatients with elevated levels of BNP. C1 Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Scirica, BM (reprint author), Dept Med, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM bscirica@partners.org NR 26 TC 86 Z9 94 U1 0 U2 2 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 JUN 6 PY 2006 VL 47 IS 11 BP 2326 EP 2331 DI 10.1016/j.jacc.2006.03.034 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 048YC UT WOS:000237981500027 PM 16750703 ER PT J AU Malm, T Ortt, M Tahtivaara, L Jukarainen, N Goldsteins, G Puolivali, J Nurmi, A Pussinen, R Ahtoniemi, T Miettinen, TK Kanninen, K Leskinen, S Vartiainen, N Yrjanheikki, J Laatikainen, R Harris-White, ME Koistinaho, M Fralutschy, SA Bures, J Koistinaho, J AF Malm, T Ortt, M Tahtivaara, L Jukarainen, N Goldsteins, G Puolivali, J Nurmi, A Pussinen, R Ahtoniemi, T Miettinen, TK Kanninen, K Leskinen, S Vartiainen, N Yrjanheikki, J Laatikainen, R Harris-White, ME Koistinaho, M Fralutschy, SA Bures, J Koistinaho, J TI beta-amyloid infusion results in delayed and age-dependent learning deficits without role of inflammation or beta-amyloid deposits SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aging; cerebrospinal fluid; learning; oxidative stress; Alzheimer's disease ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CARBOXYL-TERMINAL FRAGMENT; ALZHEIMERS-DISEASE BRAIN; APP TRANSGENIC MICE; PRECURSOR PROTEIN; RAT-BRAIN; MICROGLIAL ACTIVATION; IN-VIVO; SUPEROXIDE-DISMUTASE; COGNITIVE DEFICITS AB beta-Amyloid (A beta) polypeptide plays a critical role in the pathogenesis of Alzheimer's disease (AD), which is characterized by progressive decline of cognitive functions, formation of A beta deposits and neurofibrillary tangles, and loss of neurons. Increased genetic production or direct intracerebral administration of A beta in animal models results in A beta deposition, gliosis, and impaired cognitive functions. Whether aging renders the brain prone to A beta and whether inflammation is required for A beta-induced learning deficits is unclear. We show that intraventricular infusion of A beta(1-42) results in learning deficits in 9-month-old but not 2.5-month-old mice. Deficits that become detectable 12 weeks after the infusion are associated with a slight reduction in Cu,Zn superoxide dismutase activity but do not correlate with A beta deposition and are not associated with gliosis. In rats, A beta infusion induced learning deficits that were detectable 6 months after the infusion. Approximately 20% of the A beta immunoreactivity in rats was associated with astrocytes. NMR spectrum analysis of the animals cerebrospinal fluid revealed a strong reduction trend in several metabolites in All-infused rats, including lactate and myo-inositol, supporting the idea of dysfunctional astrocytes. Even a subtle increase in brain A beta(1-42) concentration may disrupt normal metabolism of astrocytes, resulting in altered neuronal functions and age-related development of learning deficits independent of A beta deposition and inflammation. C1 Kuopio Univ Hosp, Dept Oncol, FI-70211 Kuopio, Finland. Univ Kuopio, AI Virtanen Inst, FIN-70211 Kuopio, Finland. Univ Kuopio, Dept Chem, FIN-70211 Kuopio, Finland. Acad Sci Czech Republ, Inst Physiol, Prague 14220 4, Czech Republic. Charles Univ, Dept Psychiat, Prague 12128 2, Czech Republic. Cerebricon Ltd, FI-70210 Kuopio, Finland. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. Geriatr Res Educ & Clin Core, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. RP Bures, J (reprint author), Kuopio Univ Hosp, Dept Oncol, POB 1627, FI-70211 Kuopio, Finland. EM bures@biomed.cas.cz; jari.koistinaho@uku.fi FU BLRD VA [I01 BX000542]; NIA NIH HHS [P50 AG016570, R01 AG013741, R01 AG010685] NR 61 TC 34 Z9 35 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 6 PY 2006 VL 103 IS 23 BP 8852 EP 8857 DI 10.1073/pnas.0602896103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053BK UT WOS:000238278400049 PM 16723396 ER PT J AU Rasmussen, RA Ong, H Kittel, C Ruprecht, CR Ferrantelli, F Hu, SL Polacino, P McKenna, J Moon, J Travis, B Ruprecht, RM AF Rasmussen, RA Ong, H Kittel, C Ruprecht, CR Ferrantelli, F Hu, SL Polacino, P McKenna, J Moon, J Travis, B Ruprecht, RM TI DNA prime/protein boost immunization against HIV clade C: Safety and immunogenicity in mice (vol 24, pg 2324, 2006) SO VACCINE LA English DT Correction C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Washington, Seattle, WA 98121 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM Ruth_Ruprecht@dfci.harvard.edu RI Hu, Shiu-Lok/A-3196-2008; Ferrantelli, Flavia/J-7794-2016 OI Hu, Shiu-Lok/0000-0003-4336-7964; Ferrantelli, Flavia/0000-0002-0768-1078 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 5 PY 2006 VL 24 IS 23 BP 5092 EP 5092 DI 10.1016/j.vaccine.2006.03.069 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 056XD UT WOS:000238557500024 ER PT J AU Diaz-Griffero, F Li, X Javanbakht, H Song, B Welikala, S Stremlau, M Sodroski, J AF Diaz-Griffero, F Li, X Javanbakht, H Song, B Welikala, S Stremlau, M Sodroski, J TI Rapid turnover and polyubiquitylation of the retroviral restriction factor TRIM5 SO VIROLOGY LA English DT Article DE human immunodeficiency virus; restriction factor; TRIM5; TRIMCyp; aggresome; proteasome; ubiquitin; cytoplasmic body; tripartite motif; RBCC ID INCLUSION-BODY FORMATION; RING FINGER DOMAIN; MONKEY TRIM5-ALPHA; TRIPARTITE MOTIF; B-BOX; CYTOPLASMIC BODIES; ALPHA-SYNUCLEIN; OLD-WORLD; IN-VITRO; PROTEIN AB TRIM5 alpha and TRIMCyp are retroviral restriction factors that, like other members of the tripartite motif (TRIM) family, contain RING, B-box 2 and coiled-coil domains. We found that both proteins are rapidly turned over, with half-lives of 50-60 min. Polyubiquitylation and rapid degradation of TRIM5a depended upon intact RING and B-box 2 domains. A chimera consisting of monkey TRIM5 alpha with a RING domain of human TRIM21 exhibited a half-life of 210 min, yet potently restricted human immunodeficiency virus; therefore, rapid turnover of TRIM5 alpha is not required for its antiretroviral activity. TRIM5 alpha forms cytoplasmic bodies that contain other polyubiquitylated proteins, heat shock proteins and dynein, and thus resemble aggresome precursors. Consistent with this interpretation, proteasomal inhibitors triggered the formation of TRIM5 alpha(rh)-containing aggresomes in a micro tubule-dependent manner. Thus, TRIM5 alpha levels in the cell are maintained by continuous synthesis and rapid proteasome-mediated degradation, imbalances in which result in the formation of pre-aggresomal cytoplasmic bodies. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Dept Pathol,Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Dept Pathol,Div AIDS, 75 Francis St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009 FU NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI28691, AI063987] NR 53 TC 113 Z9 117 U1 2 U2 9 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 JUN 5 PY 2006 VL 349 IS 2 BP 300 EP 315 DI 10.1016/j.virol.2005.12.040 PG 16 WC Virology SC Virology GA 053AF UT WOS:000238274900006 PM 16472833 ER PT J AU Lehtinen, MK Yuan, ZQ Boag, PR Yang, Y Villen, J Becker, EBE DiBacco, S de la Iglesia, N Gygi, S Blackwell, TK Bonni, A AF Lehtinen, MK Yuan, ZQ Boag, PR Yang, Y Villen, J Becker, EBE DiBacco, S de la Iglesia, N Gygi, S Blackwell, TK Bonni, A TI A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span SO CELL LA English DT Article ID CAENORHABDITIS-ELEGANS; CELL-CYCLE; TRANSCRIPTION FACTORS; PROMOTES APOPTOSIS; STERILE-20 KINASE; NEURONAL SURVIVAL; PROTEIN-KINASE; HISTONE H2B; FAT-BODY; PHOSPHORYLATION AB Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. Here, we demonstrate that the protein kinase MST1 mediates oxidative-stress-induced cell death in primary mammalian neurons by directly activating the FOXO transcription factors. MST1 phosphorylates FOXO proteins at a conserved site within the forkhead domain that disrupts their interaction with 14-3-3 proteins, promotes FOXO nuclear translocation, and thereby induces cell death in neurons. We also extend the MST-FOXO signaling link to nematodes. Knockdown of the C. elegans MST1 ortholog CST-1 shortens life span and accelerates tissue aging, while overexpression of cst-1 promotes life span and delays aging. The cst-1-induced life-span extension occurs in a daf-16-dependent manner. The identification of the FOXO transcription factors as major and evolutionarily conserved targets of MST1 suggests that MST kinases play important roles in diverse biological processes including cellular responses to oxidative stress and longevity. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Biomed & Biol Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. RP Bonni, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM azad_bonni@hms.harvard.edu RI de la Iglesia, Nuria/E-1420-2015; OI de la Iglesia, Nuria/0000-0002-1083-7715; Villen, Judit/0000-0002-1005-1739 FU NIGMS NIH HHS [GM62891, R01 GM062891]; NINDS NIH HHS [NS41021] NR 45 TC 418 Z9 442 U1 4 U2 28 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 2 PY 2006 VL 125 IS 5 BP 987 EP 1001 DI 10.1016/j.cell.2006.03.046 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 050VG UT WOS:000238116400023 PM 16751106 ER PT J AU Chandrasekar, B Mummidi, S Mahimainathan, L Patel, DN Bailey, SR Imam, SZ Greene, WC Valente, AJ AF Chandrasekar, B Mummidi, S Mahimainathan, L Patel, DN Bailey, SR Imam, SZ Greene, WC Valente, AJ TI Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappa B- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; C-REACTIVE PROTEIN; ARM ASCOT-LLA; MATRIX METALLOPROTEINASES; SIGNALING PATHWAY; STATIN THERAPY; INVASIVENESS; CHOLESTEROL; DISEASE; EVENTS AB The proliferation and migration of arterial smooth muscle cells (SMCs) are key events in the vascular restenosis that frequently follows angioplasty. Furthermore, SMC migration and neointimal hyperplasia are promoted by degradation of the extracellular matrix by matrix metalloproteinases ( MMPs). Because we demonstrated previously that the proinflammatory and proatherogenic cytokine interleukin-18 (IL-18) stimulates SMC proliferation ( Chandrasekar, B., Mummidi, S., Valente, A. J., Patel, D. N., Bailey, S. R., Freeman, G. L., Hatano, M., Tokuhisa, T., and Jensen, L. E. ( 2005) J. Biol. Chem. 280, 26263 - 26277), we investigated whether IL-18 induces SMC migration in an MMP-dependent manner and whether the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin can inhibit this response. IL-18 treatment increased both mRNA and protein expression of MMP9 in human coronary artery SMCs. Gel shift, enzyme-linked immunosorbent, and chromatin immunoprecipitation assays revealed a strong induction of IL-18-mediated AP-1 (c-Fos, c-Jun, and Fra-1) and NF-kappa B (p50 and p65) activation and stimulation of MMP9 promoter-dependent reporter gene activity in an AP-1- and NF-kappa B-dependent manner. Ectopic expression of p65, c-Fos, c-Jun, and Fra-1 induced MMP9 promoter activity. Specific antisense or small interfering RNA reagents for these transcription factors reduced IL-18-mediated MMP9 transcription. Furthermore, IL-18 stimulated SMC migration in an MMP9-dependent manner. Atorvastatin effectively suppressed IL-18-mediated AP-1 and NF-kappa B-activation, MMP9 expression, and SMC migration. Together, our results indicate for the first time that the proatherogenic cytokine IL-18 induces human coronary artery SMC migration in an MMP9-dependent manner. Atorvastatin inhibits IL-18-mediated aortic SMC migration and has therapeutic potential for attenuating the progression of atherosclerosis and restenosis. C1 S Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Calif San Francisco, Gladstone Inst Virol & Immunol, Dept Immunol & Microbiol, San Francisco, CA 94158 USA. RP Chandrasekar, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chandraseka@uthscsa.edu RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 FU NHLBI NIH HHS [HL68020] NR 43 TC 128 Z9 148 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 2 PY 2006 VL 281 IS 22 BP 15099 EP 15109 DI 10.1074/jbc.M600200200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048BI UT WOS:000237922200012 PM 16554298 ER PT J AU Smith, DP Smith, DG Curtain, CC Boas, JF Pilbrow, JR Ciccotosto, GD Lau, TL Tew, DJ Perez, K Wade, JD Bush, AI Drew, SC Separovic, F Masters, CL Cappai, R Barnham, KJ AF Smith, DP Smith, DG Curtain, CC Boas, JF Pilbrow, JR Ciccotosto, GD Lau, TL Tew, DJ Perez, K Wade, JD Bush, AI Drew, SC Separovic, F Masters, CL Cappai, R Barnham, KJ TI Copper-mediated amyloid-beta toxicity is associated with an intermolecular histidine bridge SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTRON-PARAMAGNETIC-RESONANCE; ALZHEIMERS-DISEASE; HYDROGEN-PEROXIDE; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; FIBRIL FORMATION; BINDING-SITE; EPR-SPECTRA; PEPTIDE; MEMBRANE AB Amyloid-beta peptide (A beta) is pivotal to the pathogenesis of Alzheimer disease. Here we report the formation of a toxic A beta-Cu2+ complex formed via a histidine-bridged dimer, as observed at Cu2+/ peptide ratios of > 0.6:1 by EPR spectroscopy. The toxicity of the A beta-Cu2+ complex to cultured primary cortical neurons was attenuated when either the pi- or tau-nitrogen of the imidazole side chains of His were methylated, thereby inhibiting formation of the His bridge. Toxicity did not correlate with the ability to form amyloid or perturb the acyl-chain region of a lipid membrane as measured by diphenyl- 1,3,5-hexatriene anisotropy, but did correlate with lipid peroxidation and dityrosine formation. P-31 magic angle spinning solid-state NMR showed that A beta and A beta-Cu2+ complexes interacted at the surface of a lipid membrane. These findings indicate that the generation of the A beta toxic species is modulated by the Cu2+ concentration and the ability to form an intermolecular His bridge. C1 Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. Univ Melbourne, Ctr Neurosci, Melbourne, Vic 3010, Australia. Univ Melbourne, Sch Chem, Melbourne, Vic 3010, Australia. Monash Univ, Sch Phys, Clayton, Vic 3800, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Oxidat Biol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Aging Res Unit, Charlestown, MA 02129 USA. Univ Queensland, Ctr Magnet Resonance, Brisbane, Qld 4072, Australia. Univ Queensland, Ctr Met Biol, Brisbane, Qld 4072, Australia. RP Barnham, KJ (reprint author), Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. EM kbarnham@unimelb.edu.au RI Cappai, Roberto/B-3347-2010; Bush, Ashley/A-1186-2007; Separovic, Frances/D-9698-2011; OI Cappai, Roberto/0000-0002-9505-8496; Bush, Ashley/0000-0001-8259-9069; Separovic, Frances/0000-0002-6484-2763; Curtain, Cyril/0000-0001-6955-320X; Smith, David/0000-0001-5177-8574 NR 46 TC 125 Z9 131 U1 0 U2 27 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 2 PY 2006 VL 281 IS 22 BP 15145 EP 15154 DI 10.1074/jbc.M600417200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048BI UT WOS:000237922200017 PM 16595673 ER PT J AU Shen, L Guo, JJ Santos-Berrios, C Wu, MX AF Shen, L Guo, JJ Santos-Berrios, C Wu, MX TI Distinct domains for anti- and pro-apoptotic activities of IEX-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMEDIATE-EARLY GENE; EARLY-RESPONSE GENE; MITOCHONDRIAL HYPERPOLARIZATION; T-LYMPHOCYTES; HELA-CELLS; EXPRESSION; DEATH; PROTEIN; CANCER; GROWTH AB IEX-1 (immediate early response gene X-1) is a stress-inducible gene. Its overexpression can suppress or enhance apoptosis dependent on the nature of stress, yet the polypeptide does not possess any of the functional domains that are homologous to those present in well characterized effectors or inhibitors of apoptosis. This study using sequence-targeting mutagenesis reveals a transmembrane-like integrated region of the protein to be critical for both pro-apoptotic and anti-apoptotic functions. Substitution of the key hydrophobic residues with hydrophilic ones within this region impairs the capacity IEX-1 to positively and negatively regulate apoptosis. Mutations at N-linked glycosylation and phosphorylation sites or truncation of the C terminus of IEX-1 also abrogated its potential to promote cell survival. However, distinguished from the transmembrane-like domain, these mutants preserved pro-apoptotic activity of IEX-1 fully. On the contrary, mutation of nuclear localization sequence, despite its importance in apoptosis, did not impede IEX1-mediated cell survival. Strikingly, all the mutants that lose their anti-apoptotic ability are unable to prevent acute increases in production of intracellular reactive oxygen species (ROS) at the initial onset of apoptosis, whereas those mutants that can sustain anti-death function also control acute ROS production as sufficiently as wild-type IEX-1. These findings suggest a critical role of IEX-1 in regulation of intracellular ROS homeostasis, providing new insight into the mechanism underlying IEX-1-mediated cell survival. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Edwards 222,50 Blossom St, Boston, MA 02114 USA. EM mwu2@partners.org FU NIAID NIH HHS [AI050822] NR 41 TC 38 Z9 39 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 2 PY 2006 VL 281 IS 22 BP 15304 EP 15311 DI 10.1074/jbc.M600054200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048BI UT WOS:000237922200034 PM 16567805 ER PT J AU Edlow, JA Kim, S Pelletier, AJ Camargo, CA AF Edlow, JA Kim, S Pelletier, AJ Camargo, CA TI National study on emergency department visits for transient ischemic attack, 1992-2001 SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE transient cerebral ischemia; stroke; clinical guidelines ID AMERICAN-HEART-ASSOCIATION; DIFFUSION-WEIGHTED MRI; SHORT-TERM PROGNOSIS; STROKE COUNCIL; PRACTICE GUIDELINES; EARLY RISK; MANAGEMENT; ABNORMALITIES; PREVENTION; STATEMENT AB Objectives: To describe the epidemiology of U.S. emergency department (ED) visits for transient ischemic attack (TIA) and to measure rates of antiplatelet medication use, neuroimaging, and hospitalization during a ten-year time period. Methods: The authors obtained data from the 1992-2001 National Hospital Ambulatory Medical Care Survey. TIA cases were identified by having ICD-9 code 435. Results: From 1992 to 2001, there were 769 cases, representing 2,969,000 ED visits for TIA. The population rate of 1.1 ED visits per 1,000 U.S. population (95% Cl = 0.92 to 1.30) was stable over time. TIA was diagnosed in 0.3% of all ED visits. Physicians administered aspirin and other antiplatelet agents to a small percentage of patients, and 42% of TIA patients (95% Cl = 29% to 55%) received no medications at all in the ED. Too few data points existed to measure a statistically valid trend over time. Physicians performed computed tomography scanning in 56% (95% Cl = 45% to 66%) of cases and performed magnetic resonance imaging (MRI) in <5% of cases, and there was a trend toward increased imaging over time. Admission rates did not increase during the ten-year period, with 54% (95% Cl = 42% to 67%) admitted. Regional differences were noted, however, with the highest admission rate found in the Northeast (68%). Conclusions: Between 1992 and 2001, the population rate of ED visits for TIA was stable, as were admission rates (54%). Antiplatelet medications appear to be underutilized and to be discordant with published guidelines. Neuroimaging increased significantly. These findings may reflect the limited evidence base for the guidelines, educational deficits, or other barriers to guideline implementation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Emergency Med, Coordinating Ctr, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Emergency Med, Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM emnet@partners.org NR 35 TC 48 Z9 49 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2006 VL 13 IS 6 BP 666 EP 672 AR PII ISSN 1069-6563583 DI 10.1197/j.aem.2006.01.014 PG 7 WC Emergency Medicine SC Emergency Medicine GA 051NF UT WOS:000238167100013 PM 16609106 ER PT J AU Farrell, SE Pacella, C Egan, D Hogan, V Wang, E Bhatia, K Hobgood, CD AF Farrell, SE Pacella, C Egan, D Hogan, V Wang, E Bhatia, K Hobgood, CD CA Soc Acad Emergency Med Undergradua TI Resident-as-teacher: A suggested curriculum for emergency medicine SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE medical education; graduate medical education; undergraduate medical education AB Resident teaching is a competency that must be recognized, developed, and assessed. The ACGME core competencies include the role of physician as educator to "educate patients and families" and to "facilitate the learning of students and other health care professionals." Residents spend a significant proportion of their time in teaching activities, and students report achieving much of their clinical learning from their interactions with residents. Although many residents enjoy their critical role as teacher, many do not feel well prepared to teach. This article summarizes a preliminary curriculum of modules for a resident teacher-training program for emergency medicine residents. The goal of these modules is to provide learning objectives and an initial structure through which residents could improve basic teaching skills. Many of these skills are adaptable to residents' interactions with each other and with students, other healthcare professionals, and patients. Each module and corresponding teaching exercises can be found at http://www.saem.org. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Harvard Affiliated Emergency Med Residency, Boston, MA 02115 USA. Univ Pittsburgh, Med Ctr, Sch Med, Dept Emergency Med, Pittsburgh, PA USA. Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Alabama, Dept Emergency Med, Birmingham, AL USA. Northwestern Univ, Emergency Med Residency Program, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. Univ N Carolina, Sch Med, Dept Emergency Med, Chapel Hill, NC USA. RP Farrell, SE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Neville House,75 Francis St, Boston, MA 02115 USA. EM sefarrell@partners.org NR 16 TC 13 Z9 13 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2006 VL 13 IS 6 BP 677 EP 679 AR PII ISSN 1069-6563583 DI 10.1197/j.aem.2005.12.014 PG 3 WC Emergency Medicine SC Emergency Medicine GA 051NF UT WOS:000238167100015 PM 16569747 ER PT J AU Betancourt, JR AF Betancourt, JR TI Cultural competence and medical education: Many names, many perspectives, one goal SO ACADEMIC MEDICINE LA English DT Editorial Material ID CARE AB Two contemporary reports from the institute of Medicine-Crossing the Quality Chasm and Unequal Treatment-highlighted the importance of patient-centered care and cultural competence training as a means of improving the quality of health care for all and eliminating racial/ethnic disparities in health care. Previous efforts in cultural competence have aimed to teach about the attitudes, values, beliefs, and behavior of certain groups. A more effective approach is to learn a practical framework to guide inquiry with individual patients about how social, cultural, or economic factors influence their health values, beliefs, and behaviors. Rather than learning about individual cultures and their characteristics, this approach focuses on the issues that arise most commonly due to cultural differences, and how they may affect a physician's interaction with any patient. At the end of the day, physicians need a practical set of tools and skills that will enable them to provide quality care to patients everywhere, from anywhere, with whatever differences in background that may exist, in what is likely to be a brief clinical encounter. Call it what you will, the field of cultural competence aims quite simply to assure that health care providers are prepared to provide quality care to diverse populations. C1 Disparities Solut Ctr, Boston, MA USA. Inst Hlth Policy, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Betancourt, JR (reprint author), 50 Staniford St,Suite 942, Boston, MA 02114 USA. EM jbetancourt@pol.net NR 11 TC 62 Z9 64 U1 1 U2 7 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 JUN PY 2006 VL 81 IS 6 BP 499 EP 501 DI 10.1097/01.ACM.0000225211.77088.cb PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 048RB UT WOS:000237963100002 PM 16728795 ER PT J AU Gregg, J Saha, S AF Gregg, J Saha, S TI Losing culture on the way to competence: The use and misuse of culture in medical education SO ACADEMIC MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; ALTERNATIVE MEDICINE; COMMUNITY-MEDICINE; CONTROLLED-TRIAL; HEALTH; OSTEOARTHRITIS; CURRICULUM; DISEASE; SURGERY; KNEE AB Most cultural competence programs are based on traditional models of cross-cultural education that were motivated primarily by the desire to alleviate barriers to effective health care for immigrants, refugees, and others on the sociocultural margin. The main driver of renewed interest in cultural competence in the health professions has been the call to eliminate racial and ethnic disparities in the quality of health care. This mismatch between the motivation behind the design of cross-cultural education programs and the motivation behind their current application creates significant problems. First, in trying to define cultural boundaries or norms, programs may inadvertently reinforce racial and ethnic biases and stereotypes while doing little to clarify the actual complex sociocultural contexts in which patients live. Second, in attempting to address racial and ethnic disparities through cultural competence training, educators too often conflate these distinct concepts. To make this argument, the authors first discuss the relevance of culture to health and health care generally, and to disparities in particular. They then examine the concept of culture, paying particular attention to how it has been used (and misused) in cultural competence training. Finally, they discuss the implications of these ideas for health professions education. C1 Oregon Hlth & Sci Univ, Div Gen Internal Med, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Gregg, J (reprint author), Oregon Hlth & Sci Univ, Div Gen Internal Med, 3181 SW Sam Jackson Pk Rd,L-475, Portland, OR 97201 USA. EM greggj@ohsu.edu NR 43 TC 73 Z9 76 U1 2 U2 10 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 JUN PY 2006 VL 81 IS 6 BP 542 EP 547 DI 10.1097/01.ACM.0000225218.15207.30 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 048RB UT WOS:000237963100008 PM 16728802 ER PT J AU Lasky-Su, J Biederman, J Doyle, AE Wilens, T Monuteaux, M Smoller, JW Faraone, S AF Lasky-Su, J Biederman, J Doyle, AE Wilens, T Monuteaux, M Smoller, JW Faraone, S TI Family based association analysis of statistically derived quantitative traits for drug use in ADHD and the dopamine transporter gene SO ADDICTIVE BEHAVIORS LA English DT Article DE DAT; FBAT; association; phenotypes; genetics ID ATTENTION-DEFICIT HYPERACTIVITY; SUBSTANCE USE DISORDERS; SEEKING COCAINE ABUSERS; FALSE DISCOVERY RATE; PSYCHIATRIC-DISORDERS; ALCOHOL-WITHDRAWAL; BIPOLAR DISORDER; A9 ALLELE; RISK; COMORBIDITY AB Objective: To determine whether SNPs within the dopamine transporter gene (DAT) are associated with quantitative phenotypes generated from drug frequency variables in an ADHD sample. Method: 35 SNPs were genotyped in and around DAT. We developed a quantitative phenotype at each SNP by weighting the drug frequency variables. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, a screening procedure was used to select and test the SNPs with the greatest power to detect an association in DAT. Results: No SNPs in DAT were associated with the quantitative phenotypes generated from the drug frequency variables after the multiple comparisons adjustment; however, some SNPs achieved nominal significance. A sliding window of analysis of 3 SNPs also resulted in only nominal associations. Conclusions: SNPs in DAT do not appear to be associated with the phenotypes generated from drug frequency variables among individuals with ADHD. (c) 2006 Elsevier Ltd. All rights reserved. C1 SUNY Upstate Med Univ, Genet Res Program, Syracuse, NY USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. RP Faraone, S (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD37694, R01HD37999]; NIMH NIH HHS [R01MH66877] NR 65 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUN PY 2006 VL 31 IS 6 BP 1088 EP 1099 DI 10.1016/j.addbeh.2006.03.013 PG 12 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 057UM UT WOS:000238620700011 PM 16647218 ER PT J AU von Gegerfelt, AS Alicea, C Valentin, A Morrow, M van Rompay, KKA Ayash-Rashkovsky, M Markham, P Else, JG Marthas, ML Pavlakis, GN Ruprecht, RM Felber, BK AF von Gegerfelt, AS Alicea, C Valentin, A Morrow, M van Rompay, KKA Ayash-Rashkovsky, M Markham, P Else, JG Marthas, ML Pavlakis, GN Ruprecht, RM Felber, BK TI Long lasting control and lack of pathogenicity of the attenuated Rev-independent SIV in rhesus macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CONSTITUTIVE TRANSPORT ELEMENT; IN-VITRO PROPERTIES; REVERSE-TRANSCRIPTASE; POSTTRANSCRIPTIONAL REGULATION; SECONDARY STRUCTURE; RETROVIRUS TYPE-1; MOLECULAR CLONES; ADULT MACAQUES; M184V MUTATION AB A cohort of 22 rhesus macaques of Indian origin infected as neonates, juveniles, or adults by Rev-independent strains of SIV was monitored over several years. After the initial acute phase, virus replication was controlled and plasma virus loads were persistently below the threshold of the assay. The animals were monitored for up to 7.6 years after infection for viral loads, cellular and humoral immune responses, hematological changes, and overall health and no signs of immune dysfunction or AIDS were observed. This study represents several years of additional observation compared to the previously published results, and indicates that the Rev-independent SIV clones tested do not cause AIDS-like progressive disease within 7.6 years from infection. All the animals showed persistent humoral and cellular SIV-specific immune responses, consistent with chronic infection. Different Rev-independent SIV strains showed similar properties and lack of pathogenicity. Multicolor flow cytometric analysis demonstrated preservation of the Central Memory subset of T cells in the attenuated SIV-infected animals. This study demonstrates a potent, long-lasting control of the Rev-independent attenuated SIV in macaques independent of the age at virus exposure. C1 Natl Canc Inst, Canc Res Ctr, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD 21702 USA. NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. Calif Natl Primate Res Ctr, Davis, CA 95616 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Adv BioSci Labs Inc, Kensington, MD 20895 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. RP Felber, BK (reprint author), Natl Canc Inst, Canc Res Ctr, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Bldg 535,Room 209, Frederick, MD 21702 USA. EM felber@ncifcrf.gov FU NCRR NIH HHS [RR-00165, RR14180, RR00169] NR 45 TC 5 Z9 5 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 2006 VL 22 IS 6 BP 516 EP 528 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 060GA UT WOS:000238789300007 PM 16796527 ER PT J AU Buck, KJ Walter, NAR Belknap, JK Hitzemann, R AF Buck, K. J. Walter, N. A. R. Belknap, J. K. Hitzemann, R. TI Toward identification of an alcohol withdrawal quantitative trait gene (QTG) on mouse chromosome 1. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR USA. Oregon Hlth Sci Univ, Portland Alcohol Res Ctr, Portland, OR USA. Portland VA Med Ctr, Portland, OR 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 25A EP 25A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400076 ER PT J AU Kozell, LB Belknap, JK Mayeda, A Buck, KJ AF Kozell, L. B. Belknap, J. K. Mayeda, A. Buck, K. J. TI Fine mapping of two quantitative trait loci for ethanol physical dependence and associated withdrawal on mouse chromosome 1. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 25A EP 25A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400077 ER PT J AU Denmark, DL Walter, NAR Betknap, JK Hitzemann, R Buck, KJ AF Denmark, D. L. Walter, N. A. R. Betknap, J. K. Hitzemann, R. Buck, K. J. TI Candidate gene analyses of a quantitative trait locus (QTL) on mouse chromosome 1 involved in alcohol physical dependence and withdrawal. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland Alchol Res Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 26A EP 26A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400078 ER PT J AU LoCastro, JS Potter, JS Donovan, DM Couper, D Pope, KW AF LoCastro, J. S. Potter, J. Sharpe Donovan, D. M. Couper, D. Pope, K. W. TI Characteristics and implications of previously untreated alcohol dependent treatment seekers (the combine study) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02130 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 47A EP 47A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400163 ER PT J AU Kivlahan, DR Harris, AM Malte, CA Baer, JS Hawkins, E Calsyn, DA Saxon, AJ AF Kivlahan, D. R. Harris, A. M. Malte, C. A. Baer, J. S. Hawkins, E. Calsyn, D. A. Saxon, A. J. TI Three month retention in SUD specialty care predicts better 6-month abstinence: A weighted propensity score analysis. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 VA Puget Sound, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 59A EP 59A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400211 ER PT J AU Fernandez, E Koek, W Gerhardt, GA Frazer, A France, CP Strong, R AF Fernandez, E. Koek, W. Gerhardt, G. A. Frazer, A. France, C. P. Strong, R. TI Monoamine transporters, monoamine metabolism, and behavioral responses to ethanol in mitochondrial aldehyde dehydrogenase knockout mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 65A EP 65A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400237 ER PT J AU Beresford, TP Alfers, J Clapp, L Martin, B Arciniegas, D Laudenslager, M AF Beresford, T. P. Alfers, J. Clapp, L. Martin, B. Arciniegas, D. Laudenslager, M. TI Evidence for cortisol/DHEA dissociation in heavy drinkers SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Denver VA Med Ctr, Denver, CO 80220 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 76A EP 76A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400278 ER PT J AU Beresford, TP Alfers, J Clapp, L Martin, B Arciniegas, D Laudenslager, M AF Beresford, T. P. Alfers, J. Clapp, L. Martin, B. Arciniegas, D. Laudenslager, M. TI Hypercortisolism despite abstinence in heavy drinkers SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80220 USA. RI Arciniegas, David/A-3792-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 76A EP 76A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400279 ER PT J AU Veateh, LM Cummings, SE AF Veateh, L. M. Cummings, S. E. TI Impact of drug treatment on sleep during alcohol withdrawal SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Charleston Alochol Res Ctr, Charleston, SC 29425 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 79A EP 79A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400293 ER PT J AU Arciniegas, DB Hudson, C Beresford, TP AF Arciniegas, D. B. Hudson, C. Beresford, T. P. TI Comparison of the mmse and fab as screening measures for alcohol-related cognitive impairment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80220 USA. RI Arciniegas, David/A-3792-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 94A EP 94A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400353 ER PT J AU Goldstein, G Cornelius, AMJJ AF Goldstein, Gerald Cornelius, Aaron M. Jacoby jack TI Insight and cognitive function in alcoholism comorbid with bipolar disorder SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 94A EP 94A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400350 ER PT J AU Kelly, JF Humphreys, K Kehler, C AF Kelly, John F. Humphreys, Keith Kehler, Christopher TI Non-attendance and dropout from 12-step mutual-help groups: Preliminary validation of the "reasons" questionnaire SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Massachusetts Gen Hosp, Dept Psychiat, Addict Res Program, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 97A EP 97A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400362 ER PT J AU Arevalo, E Wilkemeyer, MF Shanmugasundararaj, S Charness, ME Miller, KW AF Arevalo, E. Wilkemeyer, M. F. Shanmugasundararaj, S. Charness, M. E. Miller, K. W. TI 3-azioctanol photolabels a site on the neural cell adhesion molecule, L1. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 118A EP 118A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400445 ER PT J AU Chen, S Wilkemeyer, MF Chamess, ME AF Chen, S. Wilkemeyer, M. F. Chamess, M. E. TI Ethanol inhibits NAP-induced neurite outgrowth in cerebellar neurons. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Harvard Univ, Sch Med, VA Boston Hlth Care Syst, Boston, MA 02132 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 118A EP 118A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400446 ER PT J AU Milner, L Spofford, N Buck, KJ AF Milner, L. Spofford, N. Buck, K. J. TI Baclofen-induced hypothermia in DBA/2J, C57BU/6J and congenic mouse strains. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 122A EP 122A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400463 ER PT J AU Conigliaro, J Gordon, AJ McGinnis, K Maisto, SA Justice, AC AF Conigliaro, J. Gordon, A. J. McGinnis, K. Maisto, S. A. Justice, A. C. TI Comparison of the temporal stability of alcohol use reported using the self-administered 30 day TLFB method to the phone interview method among clinical samples of HIV plus and HIV-patients. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Univ Kentucky, Lexington, KY 40506 USA. Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. Syracuse Univ, Syracuse, NY 13244 USA. Yale Univ, VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 169A EP 169A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401099 ER PT J AU Rasmussen, DD Burke, BL Crites, NJ AF Rasmussen, D. D. Burke, B. L. Crites, N. J. TI Daily nocturnal melatonin treatment prevents the decrease in thymus size induced by chronic ethanol consumption SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 173A EP 173A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401113 ER PT J AU Beresford, TP Arciniegas, DB Alfers, J Clapp, L Martin, B Du, Y Liu, D Shen, D Davatzikos, C AF Beresford, T. P. Arciniegas, D. B. Alfers, J. Clapp, L. Martin, B. Du, Y. Liu, D. Shen, D. Davatzikos, C. TI Disulfiram adherence preserves total hippocampus volume during the first 6 months of abstinence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80220 USA. RI Arciniegas, David/A-3792-2009 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 190A EP 190A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401183 ER PT J AU Durazzo, TC Studholme, C Song, E Weiner, MW Meyerhoff, DJ AF Durazzo, T. C. Studholme, C. Song, E. Weiner, M. W. Meyerhoff, D. J. TI MRI assessment of regional brain volumes in community-based heavy drinkers: The effects of chronic cigarette smoking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 San Francisco VA Med Ctr, San Francisco, CA 94121 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 194A EP 194A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401200 ER PT J AU Lieber, CS Cao, Q DeCarli, LM Leo, MA Mak, KM Ponomarenko, A Ren, C Wang, X AF Lieber, C. S. Cao, Q. DeCarli, L. M. Leo, M. A. Mak, K. M. Ponomarenko, A. Ren, C. Wang, X. TI Alcoholic liver disease is aggravated by diets containing both medium chain triglycerides (MCT) and long-chain triglycerides (LCT) but in the absence of LCT it is attenuated by MCT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Mt Sinai Sch Med, Bronx, NY 10468 USA. James J Peters VA Med Ctr, Bronx, NY 10468 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 221A EP 221A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401305 ER PT J AU Hitzemann, R Belknap, J McWeeney, S AF Hitzemann, R. Belknap, J. McWeeney, S. TI On the integration of multiple strain, short-term selective breeding (STSB), QTL and gene expression data to detect candidate quantitative trait genes for ethanol preference. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Res Serv, Portland, OR 97239 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 236A EP 236A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401363 ER PT J AU Myrick, H AF Myrick, H. TI Neuroimaging and alcohol endophenotypes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Med Univ S Carolina, Charleston Alcohol Res Ctr, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Charleston, SC 29425 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 253A EP 253A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401434 ER PT J AU Veatch, LM AF Veatch, Lynn M. TI Impact of benzodiazepine treatment on sleep during withdrawal in a mouse model of chronic alcohol exposure SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston Alcohol Res Ctr, Charleston, SC 29425 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 270A EP 270A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401502 ER PT J AU Gazdzinski, S Durazzo, TC Jahng, GH Ezekiel, F Banys, P Meyerhoff, DJ AF Gazdzinski, S Durazzo, TC Jahng, GH Ezekiel, F Banys, P Meyerhoff, DJ TI Effects of chronic alcohol dependence and chronic cigarette smoking on cerebral perfusion: A preliminary magnetic resonance study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dependence; cigarette smoking; regional brain perfusion; cerebral blood flow; magnetic resonance (MR); neurocognition ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW; NICOTINE DEPENDENCE; MAJOR DEPRESSION; GLUCOSE-METABOLISM; WORKING-MEMORY; TC-99M-BICISATE SPECT; COMPUTED-TOMOGRAPHY; BRAIN METABOLISM; SHORT-TERM AB Although approximately 80% of individuals with alcohol use disorders are chronic smokers and despite reported associations between chronic cigarette smoking and lower cerebral perfusion in nonalcoholics, previous brain perfusion studies with alcoholics did not account for the potential effects of concurrent chronic cigarette smoking. One-week-abstinent alcohol-dependent individuals in treatment (ALC) [19 smokers (sALC) and 10 nonsmokers (nsALC)] and 19 healthy light drinking, nonsmoking control participants (nsLD) were scanned with a pulsed arterial spin labeling method to measure cerebral perfusion without an exogenous contrast agent. Studies were performed with 2 different postlabeling delay times (time from labeling pulse to the excitation pulse; PLD=1,500 ms and PLD=1,200 ms) to assess the potential effect of arterial blood transit time on the perfusion. Average gray matter (GM) and white matter (WM) perfusion for the frontal and parietal lobes were calculated for each hemisphere from voxels containing at least 90% GM and 100% WM. At PLD=1,500 ms, multivariate analyses compared ALC (combined sALC and nsALC) with nsLD (p=0.04) and contrasted sALC, nsALC, and nsLD (p=0.006). ALC, as a group, showed 13% lower frontal GM perfusion (p=0.005) and 8% lower parietal GM perfusion than nsLD (p=0.03). With ALC separated into smokers and nonsmokers, sALC showed 19% lower frontal GM perfusion (p=0.001) and 12% lower parietal GM perfusion than nsLD (p=0.004). In sALC, a higher number of cigarettes smoked per day was associated with lower perfusion. Overall, regional perfusion did not differ significantly between nsALC and nsLD. Results obtained with PLD=1,200 ms generally confirmed the 1,500 ms findings. This study provides preliminary evidence that chronic cigarette smoking adversely affects cerebral perfusion in frontal and parietal GM of 1-week-abstinent alcohol-dependent individuals. These results are in line with our spectroscopic and structural magnetic resonance studies that suggest chronic cigarette smoking compounds the detrimental effects of alcohol dependence on brain neurobiology. C1 NCIRE, San Francisco, CA 94110 USA. San Francisco Vet Adm Med Ctr, Magnet Resonance Unit, San Francisco, CA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Gazdzinski, S (reprint author), NCIRE, 4150 Clement St 114M, San Francisco, CA 94110 USA. EM spg@itsa.ucsf.edu FU NIAAA NIH HHS [R01 AA010788-09, AA10788, R01 AA010788, R01 AA010788-08, R01 AA010788-11, R01 AA010788-10] NR 75 TC 21 Z9 21 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 BP 947 EP 958 DI 10.1111/j.1530-0277.2006.00108.x PG 12 WC Substance Abuse SC Substance Abuse GA 046KQ UT WOS:000237810900006 PM 16737452 ER PT J AU Sachs, G Shin, JM Howden, CW AF Sachs, G Shin, JM Howden, CW TI Review article: the clinical pharmacology of proton pump inhibitors SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 13th World Congress of Gastroenterology CY SEP, 2005 CL Montreal, CANADA ID GASTROESOPHAGEAL REFLUX DISEASE; RANDOMIZED CONTROLLED-TRIAL; ESOMEPRAZOLE 40 MG; PLASMA HALF-LIFE; GASTRIC H,K-ATPASE; ACID SUPPRESSION; INTRAGASTRIC PH; EROSIVE ESOPHAGITIS; HEALTHY-VOLUNTEERS; BINDING-SITES AB Proton pump inhibitors inhibit the gastric H+/K+-ATPase via covalent binding to cysteine residues of the proton pump. All proton pump inhibitors must undergo acid accumulation in the parietal cell through protonation, followed by activation mediated by a second protonation at the active secretory canaliculus of the parietal cell. The relative ease with which these steps occur with different proton pump inhibitors underlies differences in their rates of activation, which in turn influence the location of covalent binding and the stability of inhibition. Slow activation is associated with binding to a cysteine residue involved in proton transport that is located deep in the membrane. However, this is inaccessible to the endogenous reducing agents responsible for restoring H+/K+-ATPase activity, favouring a longer duration of gastric acid inhibition. Pantoprazole and tenatoprazole, a novel proton pump inhibitor which has an imidazopyridine ring in place of the benzimidazole moiety found in other proton pump inhibitors, are activated more slowly than other proton pump inhibitors but their inhibition is resistant to reversal. In addition, tenatoprazole has a greatly extended plasma half-life in comparison with all other proton pump inhibitors. The chemical and pharmacological characteristics of tenatoprazole give it theoretical advantages over benzimidazole-based proton pump inhibitors that should translate into improved acid control, particularly during the night. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol & Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Northwestern Univ, Feinberg Sch Med, Div Gastroenterol, Chicago, IL 60611 USA. RP Sachs, G (reprint author), WLA VAMC, 11301 Wilshire Blvd,Bldg 113,Room 324A, Los Angeles, CA 90073 USA. EM gsachs@ucla.edu NR 34 TC 126 Z9 129 U1 4 U2 19 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 JUN PY 2006 VL 23 SU 2 BP 2 EP 8 DI 10.1111/j.1365-2036.2006.02943.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 057TV UT WOS:000238619000002 PM 16700898 ER PT J AU Ioannou, GN Liou, IW Weiss, NS AF Ioannou, GN Liou, IW Weiss, NS TI Serum bilirubin and colorectal cancer risk: a population-based cohort study SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID COLON-CANCER; ALBUMIN; DAMAGE; ANTIOXIDANT; MORTALITY AB Background Bilirubin has antioxidant properties and has been postulated to protect against the development of malignancies. Aim To investigate whether baseline serum bilirubin concentration predicts the incidence of colorectal cancer in a nationally representative sample of the US population. Methods Participants of the first National Health and Nutrition Examination Survey were divided into four groups based on quartiles of baseline serum bilirubin concentration in mg/dL: < 0.38 (n = 1410), 0.38 to < 0.5 (n = 1287), 0.5 to < 0.6 (n = 1048) and >= 0.6 (n = 1742). The incidence of colorectal cancer during the following 20 years was determined from hospitalization records and death certificates. Results 110 cases of colorectal cancer-related death or hospitalization were identified among 5487 participants during 88 339 person-years of follow-up (12 per 10 000 person-years). There was no association between baseline serum bilirubin concentration and the incidence of colorectal cancer either in unadjusted analyses or after adjusting for age, gender, ethnicity, smoking, body mass index, alcohol consumption and educational attainment. Conclusions Baseline serum bilirubin concentration did not predict the subsequent incidence of colorectal cancer in this population-based cohort study. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, NW Hepatitis C Resource Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, S-111-Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu NR 20 TC 10 Z9 10 U1 0 U2 1 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 JUN 1 PY 2006 VL 23 IS 11 BP 1637 EP 1642 DI 10.1111/j.1365-2036.2006.02939.x PG 6 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 042GN UT WOS:000237516000017 PM 16696814 ER PT J AU Yeh, RW Jang, IK AF Yeh, RW Jang, IK TI Argatroban: Update SO AMERICAN HEART JOURNAL LA English DT Article ID HEPARIN-INDUCED THROMBOCYTOPENIA; PERCUTANEOUS CORONARY INTERVENTION; TISSUE-PLASMINOGEN ACTIVATOR; THROMBIN INHIBITOR; ARTERIAL THROMBOSIS; BYPASS SURGERY; ANTICOAGULATION; THERAPY; FAILURE; STROKE AB Unfractionated heparin has historically been used as the anticoagulant of choice in the management of a number of thrombotic diseases. Recognition of the limitations of heparin has led to the development of a newer class of anticoagulants, the direct thrombin inhibitors. Argatroban is a synthetic small molecule that selectively inhibits thrombin at its active site. In preclinical studies, argatroban has been shown to be more effective than heparin in preventing arterial thrombosis and in promoting vessel patency in conjunction with thrombolysis in a number of animal models. In clinical trials, argatroban has been shown to be as effective as heparin in the management of ST-segment elevation myocardial infarction in conjunction with thrombolysis. It has been shown to be an effective anticoagulant in patients undergoing percutaneous coronary interventions. In patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia complicated by thrombosis, argatroban significantly decreases the risk of thrombotic events. Small studies have demonstrated a potential role for its use in ischemic stroke and, hemodialysis. Additional studies are warranted to confirm argatroban's efficacy in a wide variety of clinical settings. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Gray Bigelow 800,55 Fruit St, Boston, MA 02114 USA. EM jiang@partners.org NR 45 TC 45 Z9 49 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2006 VL 151 IS 6 BP 1131 EP 1138 DI 10.1016/j.ahj.2005.09.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 057SD UT WOS:000238614600001 PM 16781211 ER PT J AU Boden, WE O'Rourke, RA Teo, KK Hartigan, PM Maron, DJ Kostuk, W Knudtson, M Dada, M Casperson, P Harris, CL Spertus, JA Shaw, L Chaitman, BR Mancini, J Berman, DS Weintraub, WS AF Boden, William E. O'Rourke, Robert A. Teo, Koon K. Hartigan, Pamela M. Maron, David J. Kostuk, William Knudtson, Merril Dada, Marcin Casperson, Paul Harris, Crystal L. Spertus, John A. Shaw, Leslee Chaitman, Bernard R. Mancini, John Berman, Daniel S. Weintraub, William S. CA COURAGE trial coprincipal investig TI Design and rationale of the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial: Veterans Affairs Cooperative Studies Program no. 424 SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY-DISEASE; AMERICAN-HEART-ASSOCIATION; TREATMENT PANEL-III; MEDICAL THERAPY; RANDOMIZED TRIAL; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; STABLE ANGINA; RITA-2 TRIAL; TASK-FORCE AB Background Major improvements in medical therapy and percutaneous coronary intervention (PCI) for coronary heart disease have occurred during the past decade, but no randomized trial has compared these 2 strategies for the "hard" clinical end points of death or myocardial infarction nor have earlier studies incorporated the use of coronary stents and aggressive multifaceted medical therapy during long-term follow-up. Methods The COURAGE trial is a multicenter study of patients with documented myocardial ischemia and angiographically confirmed single or multivessel coronary artery disease who are randomized to a strategy of PCI plus intensive medical therapy or intensive medical therapy alone. Medical therapy in both groups is guideline-driven and includes: aspirin, clopidogrel, simvastatin (low-density lipoprotein cholesterol target 60-85 mg/dL), long-acting metoprolol and/or amlodipine, lisinopril or losartan, and long-acting nitrates, as well as lifestyle interventions. The primary end point is a composite of all-cause mortality or acute myocardial infarction, and there will be 85% power to detect an absolute 4.6% (relative 22%) difference between strategies. The principal hypothesis is that PCI plus aggressive medical therapy (projected event rate 16.4%) will be superior to aggressive medical therapy alone (projected event rate 21%) during a 2.5- to 7-year (median of 5 years) follow-up. Conclusions COURAGE is the largest prospective randomized trial of PCI versus intensive medical therapy to date and will define the incremental benefits of PCI in the setting of contemporary optimal medical therapy for chronic coronary heart disease. A total of 2287 patients have been enrolled, and follow-up will conclude in June 2006. C1 VA Connecticut Healthcare Syst, West Haven, CT USA. Hartford Hosp, Div Cardiol, Hartford, CT 06102 USA. Univ Connecticut, Sch Med, Hartford, CT 06112 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. McMaster Univ, Hlth Sci Ctr, Hamilton, ON L8S 4L8, Canada. VA Connecticut Healthcare Syst, Vet Affairs Cooperat Studies Program Coordinating, West Haven, CT USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. London Hlth Sci Ctr, London, ON, Canada. Foothills Prov Gen Hosp, Calgary, AB T2N 2T9, Canada. Clin Res Pharm Coordinating Ctr, Vet Affairs Cooperat Studies Program, Albuquerque, NM USA. Mid Amer Heart Inst, Kansas City, MO USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. St Louis Univ, Sch Med, St Louis, MO 63103 USA. Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. Emory Univ, Emory Ctr Outcomes Res, Atlanta, GA 30322 USA. RP Boden, WE (reprint author), Hartford Hosp, Div Cardiol, 80 Seymour St, Hartford, CT 06102 USA. EM wboden@harthosp.org NR 34 TC 59 Z9 63 U1 1 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2006 VL 151 IS 6 BP 1173 EP 1179 DI 10.1016/j.ahj.2005.08.015 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 057SD UT WOS:000238614600004 PM 16781214 ER PT J AU Weintraub, WS Barnett, P Chen, S Hartigan, P Casperson, P O'Rourke, R Boden, WE Lewis, C Veledar, E Becker, E Culler, S Kolm, P Mahoney, EM Dunbar, SB Deaton, C O'Brien, B Goeree, R Blackhouse, G Nease, R Spertus, J Kaufman, S Teo, K AF Weintraub, WS Barnett, P Chen, S Hartigan, P Casperson, P O'Rourke, R Boden, WE Lewis, C Veledar, E Becker, E Culler, S Kolm, P Mahoney, EM Dunbar, SB Deaton, C O'Brien, B Goeree, R Blackhouse, G Nease, R Spertus, J Kaufman, S Teo, K TI Economics methods in the Clinical Outcomes Utilizing percutaneous coronary Revascularization and Aggressive Guideline-driven drug Evaluation (COURAGE) trial SO AMERICAN HEART JOURNAL LA English DT Article ID MULTIVARIATE PREDICTION MODEL; ST-SEGMENT ELEVATION; OF-VETERANS-AFFAIRS; COST-EFFECTIVENESS; ARTERY-DISEASE; MYOCARDIAL-INFARCTION; RAPID ESTIMATION; MEDICAL THERAPY; ANGIOPLASTY; ANGINA AB Percutaneous coronary intervention (PCI) remains a major therapeutic option for the treatment of chronic coronary artery disease. In the COURAGE trial, 2287 patients with chronic coronary disease were randomized between PCI with medical management and medical management alone. Embedded within the COURAGE trial is a detailed economic analysis being conducted in three health care systems: the US Veterans Administration (VA), Canada, and the US non-VA. Resource use and costs are being collected for each system and overall. Survival is assessed internally in the trial with mean follow-up of 4.5 years. Long-term mean survival will be estimated by projecting survival beyond the trial period by extrapolating the in-trial hazard rates. Utility is being assessed at baseline and at 1, 3, and 6 months and annually thereafter, using a computer-administered standard gamble. Quality-adjusted life years are calculated by multiplying survival by utility. The incremental cost-effectiveness ratio of PCI will be defined as the additional cost of PCI divided by the gain in life years and quality-adjusted life years. The 95% confidence regions of efficacy and costs will be determined by bootstrap over a range of acceptability thresholds, which will then be displayed in the cost-effectiveness plane and as a cost-effectiveness acceptability curve. A multilevel regression model will assess cost-effectiveness from a net benefit perspective. These approaches should provide the most detailed assessment available of the cost-effectiveness of PCI for coronary artery disease. C1 Emory Univ, Emory Ctr Outcomes Res, Atlanta, GA 30322 USA. Atlanta VA Med Ctr, Decatur, GA USA. Stanford Univ, VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Yale Univ, New Haven, CT 06520 USA. Univ Texas, S Texas Vet Healthcare Syst, San Antonio, TX 78285 USA. Hartford Hosp, Hartford, CT 06115 USA. New England Res Inst, Watertown, MA 02172 USA. Univ Manchester, Manchester M13 9PL, Lancs, England. McMaster Univ, Hamilton, ON L8S 4L8, Canada. Washington Univ, St Louis, MO 63130 USA. Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA. RP Weintraub, WS (reprint author), Emory Univ, Emory Ctr Outcomes Res, Briarcliff Campus, Atlanta, GA 30322 USA. EM wweintraub@christianacare.org RI Veledar, Emir/K-2808-2012 OI Veledar, Emir/0000-0002-3831-5433 NR 36 TC 21 Z9 21 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2006 VL 151 IS 6 BP 1180 EP 1185 DI 10.1016/j.ahj.2005.07.035 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 057SD UT WOS:000238614600005 PM 16781215 ER PT J AU Roe, MT Peterson, ED Newby, LK Chen, AY Pollack, CV Brindis, RG Harrington, RA Christenson, RH Smith, SC Califf, RM Braunwald, E Gibler, WB Ohman, EM AF Roe, MT Peterson, ED Newby, LK Chen, AY Pollack, CV Brindis, RG Harrington, RA Christenson, RH Smith, SC Califf, RM Braunwald, E Gibler, WB Ohman, EM TI The influence of risk status on guideline adherence for patients with non-ST-segment elevation acute coronary syndromes SO AMERICAN HEART JOURNAL LA English DT Article ID EARLY INVASIVE MANAGEMENT; ASSOCIATION TASK-FORCE; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; GLYCOPROTEIN IIB/IIIA; GLOBAL REGISTRY; RENAL-INSUFFICIENCY; AMERICAN-COLLEGE; ELDERLY-PATIENTS; EVENTS GRACE AB Background Practice guidelines for patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) recommend targeting evidence-based therapies for the highest-risk patients. We characterized guideline adherence for NSTE ACS by risk status. Methods We analyzed inhospital treatments and outcomes for 77760 patients with NSTE ACS (ischemic ST-segment changes and/or positive cardiac markers) included in the CRUSADE initiative from January 2001 to September 2003 at 457 US hospitals. Compliance with the American College of Card iology/American Heart Association Class I guideline recommendations for NSTE ACS was evaluated in subgroups of eligible patients without listed contraindications at increased risk for mortality and among risk categories designated by an adapted version of the PURSUIT risk model designed to predict inhospital mortality. Results Inhospital mortality was increased in patients with diabetes mellitus (5.8% vs 4.3%), renal insufficiency (10.0% vs 3.9%), signs of congestive heart failure on presentation (10.6% vs 3.1%), and age >= 75 years (8.6% vs 2.7%), compared with patients without these features. Use of guideline-recommencled acute medications, invasive cardiac procedures, and discharge medications and interventions was significantly lower in patients with these high-risk features. Patients designated as high-risk for inhospital mortality were less likely to be treated with guideline-recommended therapies compared with low-risk and moderate-risk patients. Conclusions Patients with NSTE ACS with the highest risk of mortality are less likely to receive guideline-recommended therapies and interventions. These findings highlight the need to clarify guideline recommendations for high-risk patients and to develop novel quality improvement approaches that target undertreated subgroups of patients with NSTE ACS. C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. Penn Hosp, Philadelphia, PA 19107 USA. Kaiser Permanente, Hlth Syst, San Francisco, CA USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ N Carolina, Div Cardiol, Chapel Hill, NC 27515 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Univ Cincinnati, Sch Med, Dept Emergency Med, Cincinnati, OH 45221 USA. RP Roe, MT (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, 2400 Pratt St,Room 0311 Terrace Level, Durham, NC 27705 USA. EM roe00001@mc.duke.edu NR 25 TC 84 Z9 88 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2006 VL 151 IS 6 BP 1205 EP 1213 DI 10.1016/j.ahj.2005.08.006 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 057SD UT WOS:000238614600010 PM 16781220 ER PT J AU Pinto, DS Southard, M Ciaglo, L Gibson, CM AF Pinto, DS Southard, M Ciaglo, L Gibson, CM TI Door-to-balloon delays with percutaneous coronary intervention in ST-elevation myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; INTRAVENOUS THROMBOLYTIC THERAPY; PRIMARY ANGIOPLASTY; FIBRINOLYTIC THERAPY; PROPENSITY SCORES; UNITED-STATES; TIME; REPERFUSION; TRIAL; MORTALITY AB The benefits of reperfusion in ST-elevation myocardial infarction are time-dependent no matter if epicardial blood flow is restored with primary percutaneous coronary intervention (PCI) or fibrinolysis. Rapid, sustained, and early restoration of flow in the infarct-related artery is necessary to minimize myocardial damage and to improve clinical outcomes. Though fibrinolytic therapy is widely available, it is limited by unpredictable efficacy, reinfarction, and intracranial hemorrhage. PCI has predictable success in opening the artery but is limited by delays in implementation, particularly in transfer patients. The selection of PCI or fibrinolytic therapy for ST-elevation myocardial infarction should be based on knowledge of the benefits and limitations of each strategy. While PCI is the superior strategy if employed rapidly by competent personnel, fibrinolytic therapy should be considered when significant delays to implementation of PCI are anticipated. Continued efforts, aimed at reducing the time to therapy with PCI and fibrinolysis, are of paramount importance. C1 TIMI Data Coordinating Ctr, PERFUSE Angiog Core Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02115 USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, PERFUSE Angiog Core Lab, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@perfuse.org NR 41 TC 10 Z9 12 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2006 VL 151 IS 6 SU 1 BP S24 EP S29 DI 10.1016/j.ahj.2006.04.010 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 057SE UT WOS:000238614700005 PM 16777506 ER PT J AU Morrow, DA Scirica, BM Karwatowska-Prokopczuk, E Skene, A McCabe, CH Braunwald, E AF Morrow, DA Scirica, BM Karwatowska-Prokopczuk, E Skene, A McCabe, CH Braunwald, E CA MERLIN-TIMI 36 Investigators TI Evaluation of a novel anti-ischemic agent in acute coronary syndromes: Design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial SO AMERICAN HEART JOURNAL LA English DT Article ID CHRONIC HEART-FAILURE; VENTRICULAR MYOCYTES; AMERICAN-COLLEGE; UNSTABLE ANGINA; TASK-FORCE; OXIDATION; INJURY; REPERFUSION; MANAGEMENT; INHIBITOR AB Background Despite advances in antithrombotic therapies and invasive technology, the risk of recurrent ischemic complications in patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs) remains substantial. Ranolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload and has been shown to reduce ischemia in patients with chronic stable angina. Study Design MERLIN-TIMI 36 is a phase III, randomized, double-blind, parallel-group, placebo-controlled, multinational clinical trial to evaluate the efficacy and safety of ranolazine during long-term treatment of patients with NSTE-ACS receiving standard therapy (N = 6500). Eligible patients are randomized 1:1 to ranolazine or matched placebo, initiated as 200 mg intravenously over 1 hour, followed by an 80-mg/h infusion (40 mg/h for patients with severe renal insufficiency) for up to 96 hours and oral ranolazine ER 1000 mg BID or matched placebo until the end of study. The primary end point is the time to first occurrence of any element of the composite of cardiovascular death, myocardial inforction, or recurrent ischemic. Secondary end points include ischemia on Halter monitoring, hospitalization for new or worsening heart failure, quality of life measures, and exercise performance. The evaluation of long-term safety will include death from any cause and symptomatic documented arrhythmia. Recruitment began in October 2004. The trial will continue until 730 major cardiovascular events and 3 10 deaths are recorded with expected completion in 24 to 28 months. Conclusions MERLIN-TIMI 36 will evaluate the role of ranolazine in the acute and chronic management of patients presenting with NSTE-ACS. C1 Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Dept Med, Boston, MA 02115 USA. CV Therapeut Inc, Palo Alto, CA USA. Nottingham Clin Res Ltd, Nottingham, England. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Dept Med, 75 Francis St, Boston, MA 02115 USA. NR 27 TC 1 Z9 1 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2006 VL 151 IS 6 DI 10.1016/j.ahj.2006.01.004 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 057SD UT WOS:000238614600006 ER PT J AU Bhadriraju, S Ray, KK DeFranco, AC Barber, K Bhadriraju, P Murphy, SA Morrow, DA McCabe, CH Gibson, CM Cannon, CP Braunwald, E AF Bhadriraju, S Ray, KK DeFranco, AC Barber, K Bhadriraju, P Murphy, SA Morrow, DA McCabe, CH Gibson, CM Cannon, CP Braunwald, E TI Association between blood glucose and long-term mortality in patients with acute coronary syndromes in the OPUS-TIMI 16 trial SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ELEVATION MYOCARDIAL-INFARCTION; II DIABETES-MELLITUS; STRESS HYPERGLYCEMIA; NATRIURETIC PEPTIDE; ADVERSE OUTCOMES; PROGNOSTIC VALUE; RISK AB Hyperglycemia in the context of acute coronary syndrome (ACS) is a common observation, and existing data suggest that high glucose levels are associated with increased in-hospital mortality. We assessed the relation between random glucose and long-term mortality in 9,020 patients with ACS who were enrolled in the OPUS-TIMI 16 trial. A significant relation between glucose level and 10-month mortality was observed (2.7% in quartile I vs 7.0% in quartile 4, p < 0.0001). After multivariable adjustment for co-morbidity, which included history of diabetes, this relation remained significant (quartile 4 vs 1, hazard ratio 1.70, 95% confidence interval 1.16 to 2.50, p = 0.006). These observations were similar in the TACTICS-TIMI 18 trial. In addition, we observed that B-type natriuretic peptide and troponin I levels increased across glucose quartiles in the OPUS-TIMI 16 trial (p values for trend = 0.002 and 0.0001, respectively) and the TACTICS-TIMI 18 trial (p values for trend 0.006 and 0.0001, respectively). High blood glucose during ACS is an independent predictor of long-term mortality and is significantly correlated with prognostic biomarkers. Glucose levels during ACS may be an important addition to the risk stratification of patients with ACS and a potentially important target for therapy. (c) 2006 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Michigan State Univ, McLaren Reg Med Ctr, Flint, MI USA. 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 18 TC 27 Z9 34 U1 0 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2006 VL 97 IS 11 BP 1573 EP 1577 DI 10.1016/j.amjcard.2005.12.046 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 051MX UT WOS:000238166300005 PM 16728216 ER PT J AU Saw, J Bajzer, C Casserly, IP Exaire, E Haery, C Sachar, R Lee, D Abou-Chebl, A Yadav, JS AF Saw, J Bajzer, C Casserly, IP Exaire, E Haery, C Sachar, R Lee, D Abou-Chebl, A Yadav, JS TI Evaluating the optimal activated clotting time during carotid artery stenting SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; BIVALIRUDIN AB Carotid artery stenting is an alternative to carotid endarterectomy for patients at high risk for surgery for carotid artery stenosis. Although unfractionated heparin is routinely used, there are no published data evaluating the optimal activated clotting time during carotid stenting. In a retrospective analysis of 605 patients who underwent carotid stenting using unfractionated heparin at the Cleveland Clinic Foundation, the optimal peak procedural activated. clotting time associated with the lowest combined incidence of death, stroke, or myocardial infarction was 250 to 299 seconds. (c) 2006 Elsevier Inc. All rights reserved. C1 Vancouver Gen Hosp, Vancouver, BC, Canada. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Univ Mexico, Natl Inst Hlth, Mexico City, DF, Mexico. RP Saw, J (reprint author), Vancouver Gen Hosp, Vancouver, BC, Canada. EM jsaw@interchange.ubc.ca NR 6 TC 16 Z9 18 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2006 VL 97 IS 11 BP 1657 EP 1660 DI 10.1016/j.amjcard.2005.12.062 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 051MX UT WOS:000238166300022 PM 16728233 ER PT J AU Keenan, HA Doria, A King, GL AF Keenan, H. A. Doria, A. King, G. L. TI Fifty years of diabetes without developing retinopathyh. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S7 EP S7 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900028 ER PT J AU Kupelian, V Pomerantz, M Travison, T Mohr, B Kantoff, P McKinlay, J AF Kupelian, V. Pomerantz, M. Travison, T. Mohr, B. Kantoff, P. McKinlay, J. TI Is change in testosterone levels associated with an increase in prostate cancer risk? Results from the Massachusetts Male Aging Study (MMAS). SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 New England Res Inst, Watertown, MA 02472 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Travison, Thomas/C-7098-2011 NR 0 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 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S94 EP S94 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900376 ER PT J AU Yaffe, K Steffens, D AF Yaffe, K Steffens, D TI Epidemiology of mental health: A keystone of geriatric psychiatry SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 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, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Dept Geriatr Psychiat, San Francisco, CA USA. RP Steffens, D (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3903, Durham, NC 27710 USA. EM steff001@mc.duke.edu NR 11 TC 0 Z9 0 U1 2 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2006 VL 14 IS 6 BP 477 EP 479 DI 10.1097/01.JGP.0000222934.91587.86 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 047TE UT WOS:000237900800001 PM 16731715 ER PT J AU McQueen, MB Blacker, D Laird, NM AF McQueen, MB Blacker, D Laird, NM TI Variance calculations for identity-by-descent estimation SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PAIR LINKAGE ANALYSIS; GENETIC HOMOGENEITY; ALZHEIMERS-DISEASE; BIPOLAR DISORDER; PEDIGREES; GENOME AB Nonparametric linkage strategies often involve estimation of identity by descent (IBD) with the use of affected sibling pairs. Methods for IBD estimation are well established and have been successful for mapping complex traits. However, the majority of linkage approaches involving IBD have focused on statistical testing, rather than on the effect estimates themselves. Through a bootstrap procedure developed for linkage-scan data sets, we provide standard errors for the estimated mean IBD that are broadly applicable. Applications that benefit from the availability of standard errors include effect-size estimates and confidence intervals; meta-analyses, including tests for heterogeneity; and discordant-sibling-pair evaluation. We demonstrate the use of estimated mean IBD and its standard errors in the National Institute of Mental Health Human Genetics Initiative linkage samples for bipolar disorder and Alzheimer disease. Mean IBD and its standard errors are valuable tools for the further assessment and evaluation of linkage-scan samples involving complex disease. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gerontol Res Unit, Boston, MA 02115 USA. RP McQueen, MB (reprint author), Bldg 2,Room 412,665 Huntington Ave, Boston, MA 02115 USA. EM mmcqueen@hsph.harvard.edu FU NHGRI NIH HHS [N01HG65403, N01 HG65403]; NICHD NIH HHS [R01 HD060726]; NIMH NIH HHS [R01 MH059533, 1Z01 MH002810-01, MH063445, R01 MH059545, R01 MH059548, R01 MH063445, R01 MH59533, R01 MH59545, U01 MH46282, Z01 MH002810, T32 MH017119, R01 MH59553, R01 MH59535, R01 MH059556, R01 MH059553, R01 MH059535, U01 MH46280, R01 MH059534, R01 MH059567, R01 MH060068, R01 MH59567, R01 MH60068, U01 MH46274] NR 21 TC 2 Z9 2 U1 2 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 2006 VL 78 IS 6 BP 914 EP 921 DI 10.1086/503920 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 042TZ UT WOS:000237553800002 PM 16685643 ER PT J AU Braunwald, E AF Braunwald, E TI Departments, divisions and centers in the evolution of medical schools SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. RP Braunwald, E (reprint author), TIMI Study Off, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. NR 0 TC 8 Z9 9 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 2006 VL 119 IS 6 BP 457 EP 462 DI 10.1016/j.amjmed.2005.11.025 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 050TD UT WOS:000238110500002 PM 16750955 ER PT J AU Nathan, RV Rhew, DC Murray, C Bratzler, DW Houck, PM Weingarten, SR AF Nathan, RV Rhew, DC Murray, C Bratzler, DW Houck, PM Weingarten, SR TI In-hospital observation after antibiotic switch in pneumonia: A national evaluation SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE pneumonia; antibiotics; hospital; health services research ID COMMUNITY-ACQUIRED PNEUMONIA; LOW-RISK PATIENTS; INTRAVENOUS ANTIBIOTICS; INTERVENTIONAL TRIAL; OBSERVATION PERIOD; DISCHARGE; CARE AB PURPOSE: To evaluate the clinical benefit of in-hospital observation after the switch from intravenous (IV) to oral antibiotics in a large Medicare population. Retrospective studies of relatively small size indicate that the practice of in-hospital observation after the switch from IV to oral antibiotics for patients hospitalized with community-acquired pneumonia (CAP) is unnecessary. METHODS: We performed a retrospective examination of the US Medicare National Pneumonia Project database. Eligible patients were discharged with an ICD-9-CM diagnosis consistent with community-acquired pneumonia and divided into 2 groups: 1) a "not observed" cohort, in which patients were discharged on the same day as the switch from IV to oral antibiotics and 2) an "observed for 1 day" cohort, in which patients remained hospitalized for 1 day after the switch from IV to oral antibiotics. We compared clinical outcomes between these 2 cohorts. RESULTS: A total of 39,242 cases were sampled, representing 4341 hospitals in all 50 states and the District of Columbia. There were 5248 elderly patients who fulfilled eligibility criteria involving a length of stay of no more than 7 hospital days (2536 "not observed" and 2712 "observed for 1 day" patients). Mean length of stay was 3.8 days for the "not observed" cohort and 4.5 days for the "observed for 1 day" cohort (P <.0001). There was no significant difference in 14-day hospital readmission rate (7.8% in the "not observed" cohort vs 7.2% "observed for 1 day" cohort, odds ratio 0.91; 95% confidence interval [CI] 0.74-1.12; P =. 367) and 30-day mortality rate (5.1% "not observed" cohort vs 4.4% in the "observed for 1 day" cohort, odds ratio 0.86; 95% CI, 0.67-1.11; P =. 258) between the "not observed" and "observed for 1 day" cohorts. CONCLUSIONS: Our analysis of the US Medicare Pneumonia Project database provides further evidence that the routine practice of in-hospital observation after the switch from IV to oral antibiotics for patients with CAP may be avoided in patients who are clinically stable although these findings should be verified in a large randomized controlled trial. (c) 2006 Elsevier Inc. All rights reserved. C1 Zynx Hlth Inc, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Dept Med, Los Angeles, CA USA. Cedars Sinai Med Ctr, Dept Hlth Serv Res, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Oklahoma Fdn Med Qual, Oklahoma City, OK USA. Ctr Medicare, Seattle, WA USA. Ctr Medicaid Serv, Seattle, WA USA. RP Rhew, DC (reprint author), Zynx Hlth Inc, 10880 Wilshire Blvd,Suite 1450, Los Angeles, CA 90024 USA. EM drhew@zynx.com NR 18 TC 14 Z9 16 U1 0 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUN PY 2006 VL 119 IS 6 BP 512 EP 518 DI 10.1016/j.amjmed.2005.09.012 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 050TD UT WOS:000238110500012 ER PT J AU Rhee, DJ Ramos-Esteban, JC Nipper, KS AF Rhee, DJ Ramos-Esteban, JC Nipper, KS TI Rapid resolution of topiramate-induced angle-closure glaucoma with methylprednisolone and mannitol SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EFFUSION AB PURPOSE: Topiramate-induced angle,closure glaucoma (TiACG) is believed to be related to its sulfonamide moiety. Although the exact mechanism is unknown, the time course and constellation of symptoms are consistent with a possible inflammatory pathophysiologic condition. DESIGN: Interventional case report. METHODS: We report the clinical outcome of a case of TiACG that was associated with an extreme intraocular pressure elevation of > 60 mm Hg that was treated with the combination of systemic mannitol and methylprednisolone. RESULTS: The combination of the two systemic medications resulted in the resolution of the attack with a much more rapid time course than is seen typically for extreme cases of TiACG. Mannitol treatment alone did not lower the intraocular pressure after 90 minutes, although improvement was noted four hours after methylprednisolone. CONCLUSION: For severe cases of TiACG that are associated with very high intraocular pressures, the combination of mannitol and methylprednisolone can induce a rapid improvement. Inflammation may be a component of TiACG. C1 Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. Wills Eye Hosp & Res Inst, William & Anna Goldberg Glaucoma Serv, Philadelphia, PA USA. Wills Eye Hosp & Res Inst, Cataract & Primary Care Eye Serv, Philadelphia, PA USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM dougrheee@aol.com NR 4 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2006 VL 141 IS 6 BP 1133 EP 1134 DI 10.1016/j.ajo.2006.01.021 PG 2 WC Ophthalmology SC Ophthalmology GA 056AI UT WOS:000238492600023 PM 16765687 ER PT J AU Chen, TC Cense, B Miller, JW Rubin, PAD Deschler, DG Gragoudas, ES de Boer, JF AF Chen, TC Cense, B Miller, JW Rubin, PAD Deschler, DG Gragoudas, ES de Boer, JF TI Histologic correlation of in vivo optical coherence tomography images of the human retina SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To correlate in vivo human retina optical coherence tomography (OCT)3 images with histology. DESIGN: Case series. METHODS: Linear OCT3 scans through the macula and optic nerve were obtained in three eyes of three patients who then underwent exenteration surgery for orbital cancers. OCT3 images were then correlated with histology. RESULTS: On histology, two eyes were normal, and one eye had dry macular degeneration. The plexiform layers on histology correlated with the green/yellow areas on the OCT3 scans, and the nuclear layers correlated with the black areas on the OCT3 scans. CONCLUSIONS: The authors are unaware of previous reports correlating histology to in vivo human retina OCT3 images. Our findings using human eyes are not different from previous animal studies, in that the plexiform layers are optically highly backscattering and the nuclear layers are not. C1 Harvard Univ, Glaucoma Serv, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA USA. RP Chen, TC (reprint author), Harvard Univ, Glaucoma Serv, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NEI NIH HHS [R01 EY014975, P30 EY014104] NR 6 TC 43 Z9 46 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2006 VL 141 IS 6 BP 1165 EP 1168 DI 10.1016/j.ajo.2006.01.086 PG 4 WC Ophthalmology SC Ophthalmology GA 056AI UT WOS:000238492600040 PM 16765704 ER PT J AU Hubeau, C Apostolou, I Kobzik, L AF Hubeau, C Apostolou, I Kobzik, L TI Adoptively transferred allergen-specific T cells cause maternal transmission of asthma risk SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INDUCED AIRWAY HYPERREACTIVITY; MURINE MODEL; NKT CELLS; MOUSE MODEL; CORD-BLOOD; SUSCEPTIBILITY; PREGNANCY; INFLAMMATION; CYTOKINES; TH1 AB In addition to genetics and environment, maternal asthma is an identified risk factor for developing the disease during childhood. The mechanisms of this maternal effect remain poorly understood. we tested the role of allergen-specific T cells in the maternal transmission of asthma risk by modifying a model where offspring of asthmatic mothers are more prone to develop asthma after an intentionally suboptimal asthma induction. Normal BALB/c females were injected with allergen-specific T cells from ovalbumin-specific T cell receptor (TCR) transgenic DO11.10 donors before mating. Using the protocol of suboptimal asthma induction, offspring of normal and recipient mothers were tested for their susceptibility to develop asthma. only pups of recipient mothers showed increased airway responsiveness (Penh), allergic airway inflammation with eosinophilia, and local Th2-skewed cytokine production. Although recipient mothers did not develop asthma, serum levels of interferon-gamma, interleukin (IL)-4, IL-10, and It,13 were significantly increased during pregnancy. Consistent with this finding, a subset of DO11.10 T cells persisted in the spleen and placenta of expectant recipient mothers. We conclude that allergen-specific T cells are sufficient to orchestrate the maternal transmission of asthma risk. Because overt maternal asthma was not required, our results suggest that similar maternal-fetal interactions may occur in other allergic disorders. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Physiol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP Kobzik, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Physiol Program, 665 Huntington Ave, Boston, MA 02115 USA. EM lkobzik@hsph.harvard.edu FU NHLBI NIH HHS [HL69760, R01 HL069760] NR 42 TC 16 Z9 20 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2006 VL 168 IS 6 BP 1931 EP 1939 DI 10.2353/ajpati.7.2006.051231 PG 9 WC Pathology SC Pathology GA 048YY UT WOS:000237983700015 PM 16723708 ER PT J AU Becker, CM Wright, RD Satchi-Fainaro, R Funakoshi, T Folkman, J Kung, AL D'Amato, RJ AF Becker, CM Wright, RD Satchi-Fainaro, R Funakoshi, T Folkman, J Kung, AL D'Amato, RJ TI A novel noninvasive model of endometriosis for monitoring the efficacy of antiangiogenic therapy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; PERITONEAL-FLUID; MOUSE MODEL; MURINE MODEL; AROMATASE EXPRESSION; TUMOR ANGIOGENESIS; STROMAL CELLS; FACTOR VEGF; NUDE-MOUSE AB Endometriosis, the presence of ectopic endometrial tissue, is a common disease associated with high morbidity and socioeconomic problems. Angiogenesis, the formation of new blood vessels, plays an important role in the formation and growth of endometriotic lesions. We have created a novel, noninvasive model to monitor the growth of these lesions and the associated angiogenesis in vivo. First, we generated luciferase-expressing transgenic mice by inserting the human ubiquitin C promoter coupled to the firefly luciferase reporter. Injection of luciferin in these mice causes hill-body bioluminescence, which can be detected using a low-light CCD camera. Endometrial tissue from these transgenic mice was surgically implanted into nonluminescent recipients. Bioluminescence of lesions was noninvasively imaged after intravenous or intraperitoneal injection of luciferin. Transabdominal luminescence compared well with die location of the transgenic endometriotic lesions, and lesion size correlated with the intensity of luminescence. Systemic treatment with the angiogenesis inhibitors caplostatin and endostatin peptide mP-1 delayed and suppressed the onset and intensity of the luminescent signal. Caplostatin suppressed the growth of endometriotic lesions by 59% compared with controls. This novel, noninvasive model of endometriosis provides a means to study early angiogenesis in vivo and to monitor endometriotic growth and the efficacy of systemic antiangiogenic therapy. C1 Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program,Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Dept Obstet & Gynecol, Berlin, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP D'Amato, RJ (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program,Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM robert.damato@childrens.harvard.edu RI Satchi-Fainaro, Ronit/F-9137-2011; OI Satchi-Fainaro, Ronit/0000-0002-7360-7837; Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [P01 CA045548, P01-CA45548] NR 76 TC 51 Z9 58 U1 1 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2006 VL 168 IS 6 BP 2074 EP 2084 DI 10.2353/ajpath.2006.051133 PG 11 WC Pathology SC Pathology GA 048YY UT WOS:000237983700027 PM 16723720 ER PT J AU Bauman, WA Spungen, AM Wang, J Pierson, RN Schwartz, E AF Bauman, WA Spungen, AM Wang, J Pierson, RN Schwartz, E TI Relationship of fat mass and serum estradiol with lower extremity bone in persons with chronic spinal cord injury SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE bone mineral density; bone mineral content; lean mass; estrogen; paraplegia ID HORMONE-BINDING GLOBULIN; SEX STEROID-LEVELS; BODY-COMPOSITION; MINERAL DENSITY; TURNOVER MARKERS; GROWTH-HORMONE; ELDERLY MEN/; OLDER MEN; ESTROGEN; TESTOSTERONE AB In the spinal cord injury (SCI) population, a relationship between adiposity and leg bone has not been reported, nor one between serum estradiol and leg bone mass. A cross-sectional, comparative study of 10 male pairs of monozygotic twins discordant for SCI was performed. Relationships were determined among bone mineral density (BMD), bone mineral content (BMC), lean mass, fat mass, and serum sex steroids. In the twins with SCI, significant relationships were evident between leg BMD or BMC with total body percent fat (r(2) = 0.49, P < 0.05; r(2) = 0.45, P = 0.05), leg fat mass (r(2) = 0.76, P < 0.0005; r(2) = 0.69, P = 0.005), and serum estradiol (r(2) = 0.40, P = 0.05; r(2) = 0.37, P = 0.05). By stepwise regression analysis, in the twins with SCI, leg fat mass was found to be the single most significant predictor of leg BMD or BMC (F = 12.01, r(2) = 0.76, P = 0.008; F = 50.87, r(2) = 0.86, P < 0.0001). In the able-bodied twins, leg lean mass correlated with leg BMD and BMC (r(2) = 0.58, P = 0.01; r(2) = 0.87, P = 0.0001). By use of within-pair differences, significant correlations were found for leg lean mass loss with leg BMD loss (r(2) = 0.56, P = 0.01) or leg BMC loss (r(2) = 0.64, P = 0.0005). In conclusion, in twins with SCI, significant correlations were observed between fat mass and leg BMD or BMC as well as between serum estradiol values and leg BMD. The magnitude of the leg muscle mass loss was correlated with the magnitude of bone loss. C1 Vet Affairs Med Ctr, Dept Vet Affairs, Rehabil Res & Dev Ctr Excellence, Bronx, NY USA. Vet Affairs Med Ctr, Spinal Cord Damage Res Ctr, Bronx, NY USA. Vet Affairs Med Ctr, Med Serv, Bronx, NY USA. Vet Affairs Med Ctr, Spinal Cord Injury Serv, Bronx, NY USA. Vet Affairs Med Ctr, Res Serv, Bronx, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. Columbia Univ, St Lukes Roosevelt Hosp Ctr, Body Composit Unit, New York, NY 10027 USA. RP Bauman, WA (reprint author), James J Peters Vet Affairs Med Ctr, Spinal Cord Damage Res Ctr, Rm 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM wabauman@earthlink.net NR 41 TC 12 Z9 12 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2006 VL 290 IS 6 BP E1098 EP E1103 DI 10.1152/ajpendo.00250.2005 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 046HX UT WOS:000237803300005 PM 16418207 ER PT J AU Kuhl, JE Ruderman, NB Musi, N Goodyear, LJ Patti, ME Crunkhorn, S Dronamraju, D Thorell, A Nygren, J Ljungkvist, O Degerblad, M Stahle, A Brismar, TB Andersen, KL Saha, AK Efendic, S Bavenholm, PN AF Kuhl, JE Ruderman, NB Musi, N Goodyear, LJ Patti, ME Crunkhorn, S Dronamraju, D Thorell, A Nygren, J Ljungkvist, O Degerblad, M Stahle, A Brismar, TB Andersen, KL Saha, AK Efendic, S Bavenholm, PN TI Exercise training decreases the concentration of malonyl-CoA and increases the expression and activity of malonyl-CoA decarboxylase in human muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin sensitivity; adenosine 5 '-monophosphate kinase; acetyl-coenzyme A carboxylase; peroxisome proliferator-activated receptor-gamma coactivator-1 alpha ID ACTIVATED PROTEIN-KINASE; HUMAN SKELETAL-MUSCLE; INSULIN-RESISTANCE; FAT OXIDATION; COENZYME-A; RAT; SENSITIVITY; GLUCOSE; AMPK; MITOCHONDRIAL AB The study was designed to evaluate whether changes in malonyl-CoA and the enzymes that govern its concentration occur in human muscle as a result of physical training. Healthy, middle-aged subjects were studied before and after a 12-wk training program that significantly increased Vo(2) (max) by 13% and decreased intra-abdominal fat by 17%. Significant decreases (25-30%) in the concentration of malonyl-CoA were observed after training, 24-36 h after the last bout of exercise. They were accompanied by increases in both the activity (88%) and mRNA (51%) of malonyl-CoA decarboxylase (MCD) in muscle but no changes in the phosphorylation of AMP kinase (AMPK, Thr172) or of acetyl-CoA carboxylase. The abundance of peroxisome proliferator-activated receptor (PPAR)gamma coactivator-1 alpha (PGC-1 alpha), a regulator of transcription that has been linked to the mediation of MCD expression by PPAR gamma, was also increased ( 3- fold). In studies also conducted 24 - 36 h after the last bout of exercise, no evidence of increased whole body insulin sensitivity or fatty acid oxidation was observed during an euglycemic hyperinsulinemic clamp. In conclusion, the concentration of malonylCoA is diminished in muscle after physical training, most likely because of PGC- 1 alpha- mediated increases in MCD expression and activity. These changes persist after the increases in AMPK activity and whole body insulin sensitivity and fatty acid oxidation, typically caused by an acute bout of exercise in healthy individuals, have dissipated. C1 Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden. Boston Univ Hosp, Div Res, Diabet & Metab Unit, Boston, MA 02218 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Karolinska Inst, Ersta Hosp, Dept Surg, S-17176 Stockholm, Sweden. Karolinska Inst, Neurotec, S-17176 Stockholm, Sweden. RP Kuhl, JE (reprint author), Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden. EM jeanette.kuhl@molmed.ki.se OI Saha, Asish/0000-0003-1001-5110; Brismar, Torkel/0000-0002-3409-1938; Ruderman, Neil/0000-0002-6589-6587 FU NIAMS NIH HHS [AR-42238, AR-45670]; NIDDK NIH HHS [DK-19514, DK-49147, DK-62948] NR 52 TC 32 Z9 34 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2006 VL 290 IS 6 BP E1296 EP E1303 DI 10.1152/ajpendo.00341.2005 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 046HX UT WOS:000237803300030 PM 16434556 ER PT J AU Sweeney, TR Moser, AH Shigenaga, JK Grunfeld, C Feingold, KR AF Sweeney, TR Moser, AH Shigenaga, JK Grunfeld, C Feingold, KR TI Decreased nuclear hormone receptor expression in the livers of mice in late pregnancy SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE farnesoid X receptor; liver X receptor; peroxisome proliferator-activated receptor; retinoid X receptor; lipid metabolism ID ACUTE-PHASE RESPONSE; PROLIFERATOR-ACTIVATED RECEPTORS; COACTIVATOR 1-ALPHA PGC-1-ALPHA; ELEMENT-BINDING PROTEIN-1C; X-RECEPTOR; CHOLESTEROL-METABOLISM; FATTY-ACIDS; SIGNALING PATHWAYS; LIPID HOMEOSTASIS; STEROL SYNTHESIS AB During the third trimester of pregnancy, there is an increase in serum triglyceride and cholesterol levels. The mechanisms accounting for these changes in lipid metabolism during pregnancy are unknown. We hypothesized that, during pregnancy, the expression of nuclear hormone receptors involved in regulating lipid metabolism would decrease. In 19-day pregnant mice, serum triglyceride and non-HDL cholesterol levels were significantly increased, whereas total cholesterol was slightly decreased, because of a decrease in the HDL fraction. Peroxisome proliferator-activated receptor ( PPAR)alpha, PPAR(-/-), and PPAR gamma, liver X receptor (LXR)alpha and LXR beta, farnesoid X receptor ( FXR), and retinoid X receptor (RXR)alpha, RXR beta, and RXR gamma mRNA levels were significantly decreased in the livers of 19-day pregnant mice. Additionally, the expressions of thyroid receptor (TR)alpha, pregnane X receptor, sterol regulatory element-binding proteins ( SREBP)-1a, SREBP-1c, SREBP-2, and liver receptor homolog 1 were also decreased, whereas the expression of TR beta, constitutive androstane receptor, and hepatic nuclear factor 4 showed no significant change. mRNA levels of the PPAR target genes carnitine-palmitoyl transferase 1 alpha and acyl- CoA oxidase, the LXR target genes SREBP1c, ATP-binding cassettes G5 and G8, the FXR target gene SHP, and the TR target genes malic enzyme and Spot14 were all significantly decreased. Finally, the expressions of PPAR gamma coactivator ( PGC)-1 alpha and PGC-1 alpha, known activators of a number of nuclear hormone receptors, were also significantly decreased. The decreases in expression of RXRs, PPARs, LXRs, FXR, TRs, SREBPs, and PGC-1s could contribute to the alterations in lipid metabolism during late pregnancy. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. US Dept Vet Affairs, Med Ctr, Metab Sect, San Francisco, CA USA. RP Feingold, KR (reprint author), SFVAMC Metab Sect, 4150 Clement St,111F, San Francisco, CA 94121 USA. EM kfngld@itsa.ucsf.edu NR 62 TC 23 Z9 24 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2006 VL 290 IS 6 BP E1313 EP E1320 DI 10.1152/ajpendo.00071.2005 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 046HX UT WOS:000237803300032 PM 16434558 ER PT J AU Nahrendorf, M Streif, JU Hiller, KH Hu, K Nordbeck, P Ritter, O Sosnovik, D Bauer, L Neubauer, S Jakob, PM Ertl, G Spindler, M Bauer, WR AF Nahrendorf, M Streif, JU Hiller, KH Hu, K Nordbeck, P Ritter, O Sosnovik, D Bauer, L Neubauer, S Jakob, PM Ertl, G Spindler, M Bauer, WR TI Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial perfusion and mechanics SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE magnetic resonance imaging; contractility; myocardial infarction ID LEFT-VENTRICULAR HYPERTROPHY; IN-VIVO; KNOCKOUT MICE; RAT-HEART; INFARCTION; MICROCIRCULATION; QUANTIFICATION; ISCHEMIA; MOTION; MODEL AB A decrease in the supply of ATP from the creatine kinase (CK) system is thought to contribute to the evolution of heart failure. However, previous studies on mice with a combined knockout of the mitochondrial and cytosolic CK (CK-/-) have not revealed overt left ventricular dysfunction. The aim of this study was to employ novel MRI techniques to measure maximal myocardial velocity (V-max) and myocardial perfusion and thus determine whether abnormalities in the myocardial phenotype existed in CK-/- mice, both at baseline and 4 wk after myocardial infarction (MI). As a result, myocardial hypertrophy was seen in all CK-/- mice, but ejection fraction (EF) remained normal. Vmax, however, was significantly reduced in the CK-/- mice [wild-type, 2.32 +/- 0.09 vs. CK-/-, 1.43 +/- 0.16 cm/s, P < 0.05; and wild-type MI, 1.53 +/- 0.11 vs. CK-/- MI, 1.26 +/- 0.11 cm/s, P = not significant (NS), P < 0.05 vs. baseline]. Myocardial perfusion was also lower in the CK-/- mice (wild-type, 6.68 +/- 0.27 vs. CK-/-, 4.12 +/- 0.63 ml/g (.) min, P < 0.05; and wild- type MI, 3.97 +/- 0.65 vs. CK-/- MI, 3.71 +/- 0.57 ml/g (.) min, P = NS, P < 0.05 vs. baseline), paralleled by a significantly reduced capillary density (histology). In conclusion, myocardial function in transgenic mice may appear normal when only gross indexes of performance such as EF are assessed. However, the use of a combination of novel MRI techniques to measure myocardial perfusion and mechanics allowed the abnormalities in the CK-/- phenotype to be detected. The myocardium in CK-deficient mice is characterized by reduced perfusion and reduced maximal contraction velocity, suggesting that the myocardial hypertrophy seen in these mice cannot fully compensate for the absence of the CK system. C1 Univ Wurzburg, Med Klin & Poliklin 1, D-97080 Wurzburg, Germany. Univ Wurzburg, Inst Phys, D-97080 Wurzburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX1 2JD, England. RP Bauer, WR (reprint author), Univ Wurzburg, Med Klin & Poliklin 1, Josef Schneider Str 2, D-97080 Wurzburg, Germany. EM bauer_w@medizin.uni-wuerzburg.de RI Neubauer, Stefan/B-8448-2011; OI Jakob, Peter/0000-0002-3481-5545 NR 28 TC 38 Z9 39 U1 0 U2 0 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 JUN PY 2006 VL 290 IS 6 BP H2516 EP H2521 DI 10.1152/ajpheart.01038.2005 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 040YQ UT WOS:000237419600046 PM 16415075 ER PT J AU Meyer, AM Dwyer-Nield, LD Hurteau, G Keith, RL Ouyang, Y Freed, BM Kisley, LR Geraci, MW Bonventre, JV Nemenoff, RA Malkinson, AM AF Meyer, AM Dwyer-Nield, LD Hurteau, G Keith, RL Ouyang, Y Freed, BM Kisley, LR Geraci, MW Bonventre, JV Nemenoff, RA Malkinson, AM TI Attenuation of the pulmonary inflammatory response following butylated hydroxytoluene treatment of cytosolic phospholipase A(2) null mice SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE eicosanoids; Clara cells; macrophages ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; PLATELET-ACTIVATING-FACTOR; CHEMOKINE RECEPTOR; LUNG TUMORIGENESIS; EPITHELIAL-CELLS; TRANSGENIC MICE; II CELLS; EXPRESSION; CYTOKINE; MACROPHAGES AB Administration of butylated hydroxytoluene (BHT) to mice causes lung damage characterized by the death of alveolar type I pneumocytes and the proliferation and subsequent differentiation of type II cells to replace them. Herein, we demonstrate this injury elicits an inflammatory response marked by chemokine secretion, alveolar macrophage recruitment, and elevated expression of enzymes in the eicosanoid pathway. Cytosolic phospholipase A(2) (cPLA(2)) catalyzes release of arachidonic acid from membrane phospholipids to initiate the synthesis of prostaglandins and other inflammatory mediators. A role for cPLA(2) in this response was examined by determining cPLA(2) expression and enzymatic activity in distal respiratory epithelia and macrophages and by assessing the consequences of cPLA(2) genetic ablation. BHT-induced lung inflammation, particularly monocyte infiltration, was depressed in cPLA(2) null mice. Monocyte chemotactic protein-1 (MCP-1) content in bronchoalveolar lavage fluid increases after BHT treatment but before monocyte influx, suggesting a causative role. Bronchiolar Clara cells isolated from cPLA(2) null mice secrete less MCP-1 than Clara cells from wild-type mice, consistent with the hypothesis that cPLA(2) is required to secrete sufficient MCP-1 to induce an inflammatory monocytic response. C1 Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Div Pulm Sci & Crit Care Med, Dept Med, Denver, CO USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Nephrol, Charlestown, MA USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Charlestown, MA USA. RP Malkinson, AM (reprint author), Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Box C238,4200 E 9th Ave, Denver, CO 80262 USA. EM al.malkinson@uchsc.edu FU NCI NIH HHS [CA 93641, CA 33497] NR 43 TC 10 Z9 10 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUN PY 2006 VL 290 IS 6 BP L1260 EP L1266 DI 10.1152/ajplung.00182.2005 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 040VG UT WOS:000237408200025 PM 16443645 ER PT J AU Fu, Y Subramanya, A Rozansky, D Cohen, DM AF Fu, Y Subramanya, A Rozansky, D Cohen, DM TI WNK kinases influence TRPV4 channel function and localization SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE hypertension; calcium balance; hypotonicity; osmoregulation ID CATION CHANNEL; LARGE FAMILY; MUTANT WNK4; HYPERTENSION; PROTEIN; EPITHELIA; KIDNEY; HYPERCALCIURIA; IDENTIFICATION; HYPERKALEMIA AB TRPV4, a renally expressed nonselective cation channel of the transient receptor potential (TRP) family, is gated by hypotonicity. Kinases of the WNK family influence expression and function of the thiazide-sensitive Na(+)-Cl(-) cotransporter, and monogenic human hypertension has been linked to mutations in the gene coding for WNK4. Along with TRPV4, WNK isoforms are highly expressed in the distal nephron. We show here that coexpression of WNK4 downregulates TRPV4 function in human embryonic kidney (HEK-293) cells and that this effect is mediated via decreased cell surface expression of TRPV4; total abundance of TRPV4 in whole cell lysates is unaffected. The effect of the related kinase WNK1 on TRPV4 function and surface expression was similar to that of WNK4. Disease-causing point mutations in WNK4 abrogate, but do not eliminate, the inhibitory effect on TRPV4 function. In contrast to wild-type WNK4, a kinase-dead WNK4 point mutant failed to influence TRPV4 trafficking; however, deletion of the entire WNK4 kinase domain did not blunt the effect of WNK4 on localization of TRPV4. Deletion of the extreme COOH-terminal putative coiled-coil domain of WNK4 abolished its effect. In immunoprecipitation experiments, we were unable to detect direct interaction between TRPV4 and either WNK kinase. In aggregate, these data indicate that TRPV4 is functionally regulated by WNK family kinases at the level of cell surface expression. Because TRPV4 and WNK kinases are coexpressed in the distal nephron in vivo and because there is a tendency toward hypercalcemia in TRPV4(-/-) mice, we speculate that this pathway may impact systemic Ca(2+) balance. In addition, because WNK kinases and TRPV4 are activated by anisotonicity, they may comprise elements of an osmosensing or osmotically responsive signal transduction cascade in the distal nephron. C1 Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Nephrol, Dept Pediat, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Cohen, DM (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, Mailcode PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM cohend@ohsu.edu NR 45 TC 50 Z9 52 U1 1 U2 3 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 JUN PY 2006 VL 290 IS 6 BP F1305 EP F1314 DI 10.1152/ajprenal.00391.2005 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 040HC UT WOS:000237368600005 PM 16403833 ER PT J AU Gelasco, AK Raymond Jr AF Gelasco, AK Raymond, JR TI Indoxyl sulfate induces complex redox alterations in mesangial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE electron paramagnetic spin resonance; fluorescence; microphysiometry; superoxide; NADPH oxidase; reactive oxygen species; uremic toxins ID ORGANIC ANION TRANSPORTERS; ACTIVATED PROTEIN-KINASE; HUMAN SERUM-ALBUMIN; SUPEROXIDE RADICALS; UREMIC TOXIN; RENAL-FAILURE; DIABETIC RATS; ORAL SORBENT; SPIN-TRAP; IN-VIVO AB Indoxyl sulfate is a protein metabolite that is concentrated in the serum of patients with chronic renal insufficiency. It also is a uremic toxin that has been implicated in the progression of chronic renal disease in rodent models. We have shown previously that mesangial cell redox status is related to activation of mitogen-activated protein kinases and cell proliferation, which are factors related to glomerular damage. We used three methods to examine the ability of indoxyl sulfate to alter mesangial cell redox as a possible mechanism for its toxicity. Indoxyl sulfate increases mesangial cell reduction rate in a concentration-dependent manner as demonstrated by redox microphysiometry. Alterations occurred at concentrations as low as 100 mu M, with more marked alterations occurring at higher concentrations associated with human renal failure. We demonstrated that indoxyl sulfate induces the production of intracellular reactive oxygen species (ROS) in mesangial cells (EC(50) = 550 mu M) by using the ROS-sensitive fluorescent dye CM-DCF. ROS generation was only partially (similar to 50%) inhibited by the NADPH oxidase inhibitor diphenylene iodinium at low (<= 300 mu M) indoxyl sulfate concentrations. Diphenylene iodinium was without effect at higher concentrations of indoxyl sulfate. We also used electron paramagnetic spin resonance spectroscopy with extracellular and intracellular spin traps to show that indoxyl sulfate increases extracellular SOD-sensitive O(2)(-)center dot production and intracellular hydroxyl radical production that may derive from an initial O(2)(-)center dot burst. These results document that indoxyl sulfate, when applied to renal mesangial cells at pathological concentrations, induces rapid and complex changes in mesangial cell redox. C1 Med Univ S Carolina, Div Nephrol, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. RP Gelasco, AK (reprint author), Med Univ S Carolina, Div Nephrol, Dept Med, 96 Jonathan Lucas St,829 CSB, Charleston, SC 29425 USA. EM gelascoa@musc.edu FU NCRR NIH HHS [S10RR-13005, S10RR-13656]; NIDDK NIH HHS [DK-54720, DK-59950] NR 42 TC 67 Z9 69 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 JUN PY 2006 VL 290 IS 6 BP F1551 EP F1558 DI 10.1152/ajprenal.00281.2004 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 040HC UT WOS:000237368600034 PM 16434574 ER PT J AU Stoddard, FJ Ronfeldt, H Kagan, J Drake, JE Snidman, N Murphy, JM Saxe, G Burns, J Sheridan, RL AF Stoddard, Frederick J. Ronfeldt, Heidi Kagan, Jerome Drake, Jennifer E. Snidman, Nancy Murphy, J. Michael Saxe, Glenn Burns, Jennifer Sheridan, Robert L. TI Young burned children: The course of acute stress and physiological and Behavioral responses SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CHILDHOOD DERIVATIVES; PTSD SYMPTOMS; ADOLESCENTS; DISORDER; INHIBITION; TRAUMA; AGE; TEMPERAMENT; DEPRESSION AB Objective: Symptoms of posttraumatic stress disorder ( PTSD) are a focus of much research with older children, but little research has been conducted with young children, who account for about 40% of all pediatric burn injuries. This is a longitudinal study of 72 acutely burned children (12 - 48 months old) that assessed the course of acute posttraumatic symptoms and physiological reactivity. Method: Parents were interviewed shortly after their child was admitted to the hospital and 1 month after discharge. PTSD symptoms were measured with the Diagnostic Interview for Children and Adolescents (DICA) module. Nurses recorded the child's physiological data throughout the hospital stay. The child's physical and behavioral responses were assessed in a laboratory at about 1 month after discharge. Results: Reduced social smiling in the children was related to PTSD symptoms, as measured by the DICA, and heart rate at 24 hours and 7 days. Reduced vocalization was related to the child's rating of pain at 24 hours. Smiling and vocalizations were also related to some DICA cluster scores but not avoidance. Conclusions: Preschool children admitted to a burn unit demonstrated PTSD symptoms and physiological reactivity. There was a relation to the frequency of smiles and vocalizations. C1 Shriners Burn Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Stoddard, FJ (reprint author), Shriners Burn Hosp, 51 Blossom St, Boston, MA 02114 USA. EM fstoddard@partners.org NR 44 TC 28 Z9 28 U1 6 U2 10 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 JUN PY 2006 VL 163 IS 6 BP 1084 EP 1090 DI 10.1176/appi.ajp.163.6.1084 PG 7 WC Psychiatry SC Psychiatry GA 048UP UT WOS:000237972300022 PM 16741210 ER PT J AU Linas, BP Zheng, H Losina, E Walensky, RP Freedberg, KA AF Linas, BP Zheng, H Losina, E Walensky, RP Freedberg, KA TI Assessing the impact of federal HIV prevention spending on HIV testing and awareness SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID RISK BEHAVIORS; INFECTION AB Objectives. The United States allocates more than $900 million annually for the prevention of HIV infection. We assessed the impact of this funding on HIV testing and knowledge. Methods. We linked data from the Behavioral Risk Factor Surveillance System with tracking of Centers for Disease Control and Prevention (CDC) HIV prevention funding. We developed and validated regression models of the relation between HIV prevention funding to a respondent's state and the odds that the respondent (1) had been tested for HIV, and (2) was aware of methods to prevent mother-to-child HIV transmission (MTCT). Results. The odds of having been tested for HIV increased with increased CDC funding to states (P=.009), as did awareness of prevention of MTCT (P=.002). We estimate that CDC HIV prevention funds led to 12.8 million more people being tested for HIV between 1998 and 2003 than would have been tested had all states received funds equal to the lowest quintile of funding. Conclusions. Federal HIV prevention funds independently correlate with increased HIV testing and knowledge of prevention of MTCT. Proposed reductions in HIV prevention spending would likely have adverse public health consequences. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Ctr AIDS Res, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP Linas, BP (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM blinas@partners.org FU NIAID NIH HHS [K25 AI050436, K23 AI001794, K23 AI01794, P30 AI060354, K24 AI062476, K25 AI50436]; PHS HHS [T32 HP11001-18] NR 26 TC 10 Z9 10 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2006 VL 96 IS 6 BP 1038 EP 1043 DI 10.2105/AJPH.2005.074344 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 047UY UT WOS:000237905400026 PM 16670217 ER PT J AU Walker, JKL Ahumada, A Frank, B Gaspard, R Berman, K Quackenbush, J Schwartz, DA AF Walker, JKL Ahumada, A Frank, B Gaspard, R Berman, K Quackenbush, J Schwartz, DA TI Multistrain genetic comparisons reveal CCR5 as a receptor involved in airway hyperresponsiveness SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE airway hyperresponsiveness; asthma; CCR5; microarray; multistrain ID MICROARRAY ANALYSIS; CLUSTER-ANALYSIS; MESSENGER-RNA; PROTEIN; INFLAMMATION; CHEMOKINES; ASTHMA; ACTIVATION; DISEASE; LIGASES AB Asthma is a ubiquitous disease with a broad range of clinical phenotypes. To better understand the complex genetic and environmental interactions underlying asthma, we compared the gene-gene interactions of four genetically distinct mouse strains that demonstrate biologically distinct responses to allergen. Using DNA microarrays and knock-out mouse studies, we showed that CCR5 plays a definitive role in the development of ovalbumin-induced allergic airway inflammatory disease. In addition, gene expression profiling data have revealed other potential novel targets for therapeutics-based research and has enhanced the understanding of the molecular mechanisms underlying the etiology of "asthma." C1 Duke Univ, Med Ctr, Dept Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. Inst Genom Res, Rockville, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Walker, JKL (reprint author), Duke Univ, Med Ctr, Dept Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. EM walke082@mc.duke.edu FU NHLBI NIH HHS [U01 HL66580-01] NR 39 TC 8 Z9 9 U1 1 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 2006 VL 34 IS 6 BP 711 EP 718 DI 10.1165/rcmb.2005-0314OC PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 048QT UT WOS:000237962300012 PM 16474097 ER PT J AU Wade, AA Scott, JA Kuter, I Fischman, AJ AF Wade, AA Scott, JA Kuter, I Fischman, AJ TI Flare response in F-18-fluoride ion PET bone scanning SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast cancer; oncologic imaging; PET/CT; spine; vertebral column ID METASTASES; THERAPY C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. RP Wade, AA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 216, Boston, MA 02114 USA. NR 6 TC 31 Z9 33 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 JUN PY 2006 VL 186 IS 6 BP 1783 EP 1786 DI 10.2214/AJR.05.0225 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 045RI UT WOS:000237759300043 PM 16714674 ER PT J AU Wittram, C Kalra, MK Maher, MM Greenfield, A McLoud, TC Shepard, JAO AF Wittram, C Kalra, MK Maher, MM Greenfield, A McLoud, TC Shepard, JAO TI Acute and chronic pulmonary emboli: Angiography-CT correlation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cardiovascular disease; conventional angiography; CT angiography; embolism; lung; thromboembolic disease ID DIAGNOSIS AB OBJECTIVE. The objective of our study was to review the classic direct and indirect angiographic signs of acute and chronic pulmonary embolism (PE) and correlate these findings with MDCT. CONCLUSION. CT and angiography have complementary roles in the accurate diagnosis of acute and chronic thromboembolic disease. Conventional angiography should be used as a problem-solving technique after CT angiography has been performed because CT angiography is less invasive. C1 Massachusetts Gen Hosp, Dept Thorac Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Dept Thorac Radiol, Founders 202,55 Fruit St, Boston, MA 02115 USA. EM cwittram@partners.org NR 9 TC 35 Z9 37 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 JUN PY 2006 VL 186 IS 6 SU S BP S421 EP S429 DI 10.2214/AJR.04.1955 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 047AE UT WOS:000237851400014 PM 16714619 ER PT J AU Katz, A Gage, I Evans, S Shaffer, M Fleury, T Smith, FP Flax, R Drogula, C Petrucci, P Magnant, C AF Katz, A Gage, I Evans, S Shaffer, M Fleury, T Smith, FP Flax, R Drogula, C Petrucci, P Magnant, C TI Sentinel lymph node positivity of patients with ductal carcinoma in situ or microinvasive breast cancer SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE sentinel lymph node; ductal carcinoma in situ ID BIOPSY; METASTASES; DCIS; MANAGEMENT; DIAGNOSIS AB Purpose: The purpose of this study was to determine the rates of sentinel lymph node (SLN) positivity in patients with a final diagnosis of ductal carcinoma in situ (DCIS) or microinvasive breast cancer (MIC). Methods: One hundred thirty patients underwent SLN mapping from 1998 to 2003 for DCIS or MIC. Results: One hundred nine patients with DCIS and 21 with MIC underwent SLN mapping. One patient with bilateral DCIS underwent 2 SLN procedures; therefore, the results of 131 SLN procedures are included. On hematoxylin and eosin (H&E) staining, 4 of 110 patients (3.6%) with DCIS had positive SLNs. Four additional patients had positive SLNs by IHC staining only (3.6%). Two of 8 patients underwent completion axillary dissection, and neither had additional involved nodes on completion axillary dissection. One of the 21 patients with MIC had positive SLNs by hematoxylin and eosin (H&E) (4.8%), and another had an involved SLN by IHC staining (4.8%). The patient with the positive SLN by H&E had 1 additional node on completion axillary dissection. Conclusion: Rates of SLN positivity for patients with DCIS are modest, even in a high-risk population, and there is continuing uncertainty about its clinical importance. (c) 2006 Excerpta Medica Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Sibley Mem Hosp, Washington, DC USA. RP Katz, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 31, Boston, MA 02114 USA. EM abkatz@partners.org NR 21 TC 41 Z9 44 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUN PY 2006 VL 191 IS 6 BP 761 EP 766 DI 10.1016/j.amjsurg.2006.01.019 PG 6 WC Surgery SC Surgery GA 047GY UT WOS:000237869000008 PM 16720145 ER PT J AU Schwartz, BS Harris, JB Khan, AI Larocque, RC Sack, DA Malek, MA Faruque, ASG Qadri, F Calderwood, SB Luby, SP Ryan, ET AF Schwartz, Brian S. Harris, Jason B. Khan, Ashraful I. Larocque, Regina C. Sack, David A. Malek, Mohammad A. Faruque, Abu S. G. Qadri, Firdausi Calderwood, Stephen B. Luby, Stephen P. Ryan, Edward T. TI Diarrheal epidemics in Dhaka, Bangladesh, during three consecutive floods: 1988, 1998, and 2004 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ORAL CHOLERA VACCINATION; VIBRIO-CHOLERAE; HYPERINFECTIVITY; SURVEILLANCE; DISASTERS AB We examined demographic, microbiologic, and clinical data from patients presenting during 1988, 1998, and 2004 flood-associated diarrheal epidemics at a diarrhea treatment hospital in Dhaka, Bangladesh. Compared with non-flood periods, individuals presenting during flood-associated epidemics were older, more severely dehydrated, and of lower socioeconomic status. During flood-associated epidemics, Vibrio cholerae was the most commonly identified cause of diarrhea, and the only diarrheal pathogen whose incidence proportionally increased in each epidemic compared with seasonally matched periods. Rotavirus was the second most frequently identified flood-associated pathogen, although the proportion of cases caused by rotavirus infection decreased during floods compared with matched periods. Other causes of diarrhea did not proportionally change, although more patients per day presented with enterotoxigenic Escherichia coli, Shigella, and Salmonella species-associated diarrhea during floods compared with matched periods. Our findings suggest that cholera is the predominant cause of flood-associated diarrheal epidemics in Dhaka, but that other organisms spread by the fecal-oral route also contribute. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. ICDDRB, Ctr Hlth & Populat Res, Dhaka, Bangladesh. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Schwartz, BS (reprint author), Univ Calif San Francisco, Mt Zion Hosp, Box 1945,Room 532W,1600 Divisadero St, San Francisco, CA 94115 USA. EM bschwartz@medicine.ucsf.edu FU FIC NIH HHS [K01 TW007144, K01-TW07144]; NIAID NIH HHS [U01-AI58935, U01 AI058935, T32 AI007061, R01 AI040725, AI40725]; NICHD NIH HHS [K12 HD000850, K12-HD00850] NR 25 TC 73 Z9 80 U1 1 U2 9 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 2006 VL 74 IS 6 BP 1067 EP 1073 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 051ZT UT WOS:000238200900024 PM 16760521 ER PT J AU Romano, DM Dong, YL Hiltunen, M Tanzi, RE Xie, ZC AF Romano, Donna M. Dong, Yuanlin Hiltunen, Mikko Tanzi, Rudolph E. Xie, Zhongcong TI Artefactual effects of lipid-based cell transfection reagents on A beta PP processing and A beta production SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article DE TKO; FuGene6; RNAifect; Electroporation; A beta PP processing; A beta production ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; GAMMA-SECRETASE; GENE-TRANSFER; CHOLESTEROL; CLEAVAGE; GENERATION; MECHANISMS; PEPTIDE; NOTCH AB The study of amyloidogenic beta-amyloid precursor protein (A beta PP) metabolism and amyloid beta protein (A beta) production has been a major focus of Alzheimer's disease (AD) neuropathogenesis research. Cell transfection is a commonly employed method for assessing the effects of various genes on A beta PP processing and A beta production. Certain cell transfection reagents utilize lipid-based formulations that could potentially affect A beta PP processing and A beta production. Thus, we set out to assess the effects of cell transfection reagents with lipid formulations (TKO, FuGene6, RNAifect) on A beta PP processing and A beta level in H4 human neuroglioma cells overexpressing human A beta PP. We found both TKO and RNAifect increase the protein levels of A beta PP-C-terminal fragments (CTFs) and A beta levels, while FuGene6 increases the protein levels of A beta PP-CTFs without altering A beta level. In contrast, electroporation-based cell transfection does not affect A beta PP processing and A beta production in our studies. These results suggest for the first time that lipid-based cell transfection reagents may artefactually affect A beta PP processing and A beta production, thereby confounding studies aimed at assessing the effects of transfected genes on A beta PP metabolism. C1 Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, 114 10th St,3725M, Charlestown, MA 02129 USA. EM zxie@partners.org FU NIA NIH HHS [K12 (AG 00294-17), AG 014713-07, P60 (AG008812-15)]; NIMH NIH HHS [MH 60009-03]; NINDS NIH HHS [K08 (NS048140-01)] NR 29 TC 1 Z9 1 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD JUN PY 2006 VL 13 IS 2 BP 86 EP 92 DI 10.1080/13506120600722605 PG 7 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 090DW UT WOS:000240931800004 PM 16911962 ER PT J AU Rowe, BH Camargo, CA AF Rowe, Brian H. Camargo, Carlos A., Jr. TI Emergency department treatment of severe acute asthma SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material C1 Univ Alberta, Dept Emergency Med, Fac Med & Dent, Edmonton, AB T6G 2B7, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Rowe, BH (reprint author), Univ Alberta, Dept Emergency Med, Fac Med & Dent, Room 1G1-42 WMC,8440-112 St, Edmonton, AB T6G 2B7, Canada. EM brian.rowe@ualberta.ca NR 20 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUN PY 2006 VL 47 IS 6 BP 564 EP 566 DI 10.1016/j.annemergmed.2006.02.008 PG 3 WC Emergency Medicine SC Emergency Medicine GA 048RN UT WOS:000237964300010 PM 16713786 ER PT J AU Brown, RH Amato, A AF Brown, RH Amato, A TI Calpainopathy and eosinophilic myositis SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID INFLAMMATORY MYOPATHY; MUSCULAR-DYSTROPHY; MUSCLE-FIBERS; T-CELLS; POLYMYOSITIS; PERIMYOSITIS; LYMPHOCYTES C1 Massachusetts Gen Hosp, Neurol Serv, Charlestown, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. RP Brown, RH (reprint author), Massachusetts Gen Hosp, Neurol Serv, Charlestown, MA USA. NR 29 TC 17 Z9 17 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2006 VL 59 IS 6 BP 875 EP 877 DI 10.1002/ana.20900 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 049YV UT WOS:000238054800004 PM 16718709 ER PT J AU Pestalozzi, BC Zahrieh, D Price, KN Holmberg, SB Lindtner, J Collins, J Crivellari, D Fey, MF Murray, E Pagani, O Simoncini, E Castiglione-Gertsch, M Gelber, RD Coates, AS Goldhirsch, A AF Pestalozzi, BC Zahrieh, D Price, KN Holmberg, SB Lindtner, J Collins, J Crivellari, D Fey, MF Murray, E Pagani, O Simoncini, E Castiglione-Gertsch, M Gelber, RD Coates, AS Goldhirsch, A CA Int Breast Canc Study Grp TI Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG) SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; central nervous system; adjuvant chemotherapy; competing risks; CMF; metastases ID TRASTUZUMAB-BASED THERAPY; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; FAILURE PROBABILITIES; COMPETING RISK; COMBINATION; INVOLVEMENT; EXPRESSION; SURVIVAL; BRAIN AB Background: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified. Patients and methods: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time. Results: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%). Conclusion: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases. C1 Univ Zurich Hosp, Dept Oncol, CH-8091 Zurich, Switzerland. European Inst Oncol, Milan, Italy. Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. Canc Council Australia, Australian New Zealand Breast Canc Trials Grp, Sydney, NSW, Australia. Univ Bern, Inselspital, Inst Med Oncol, CH-3010 Bern, Switzerland. Univ Bern, Inselspital, IBCSG Coordinating Ctr, CH-3010 Bern, Switzerland. Oncol Med Spedali Civili, Brescia, Italy. Swiss Grp Clin Canc Res, Brescia, Italy. Oncol Inst So Switzerland, Lugano, Switzerland. Univ Cape Town, ZA-7700 Rondebosch, South Africa. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. Univ Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Royal Melbourne Hosp, Dept Surg, Australian New Zealand Breast Canc Trials Grp, Melbourne, Vic, Australia. Inst Oncol, Dept Surg, Ljubljana, Slovenia. SU Moelndals Hosp, Dept Surg, Molndal, Sweden. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Dana Farber Canc Inst, IBCSG, Ctr Stat, Boston, MA 02115 USA. RP Pestalozzi, BC (reprint author), Univ Zurich Hosp, Dept Oncol, Ramistr 100, CH-8091 Zurich, Switzerland. EM bernhard.pestalozzi@usz.ch NR 28 TC 182 Z9 191 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2006 VL 17 IS 6 BP 935 EP 944 DI 10.1093/annonc/mdl064 PG 10 WC Oncology SC Oncology GA 044TT UT WOS:000237696000009 PM 16603601 ER PT J AU Hur, C Chan, AT Tramontano, AC Gazelle, GS AF Hur, C Chan, AT Tramontano, AC Gazelle, GS TI Coxibs versus combination NSAID and PPI therapy for chronic pain: An exploration of the risks, benefits, and costs SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE chronic pain; nonsteroidal antiinflammatory drugs; proton pump inhibitors; selective coxibs ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIAL; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR THROMBOTIC EVENTS; PLACEBO-CONTROLLED TRIAL; CORONARY HEART-DISEASE; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; GASTROINTESTINAL TOXICITY; COX-2 INHIBITORS AB OBJECTIVE: To systematically review studies qualitatively to compare the risks (gastrointestinal [GI] and cardiovascular) and benefits (pain control) of cyclooxygenase-2 inhibitors (coxibs) relative to an alternative therapy of a nonselective nonsteroidal antiinflammatory drug (NSAID) combined with a proton-pump inhibitor (PPI) and explore circumstances when coxibs may be appropriate. METHODS: Relevant studies were identified through a search of MEDLINE (Ovid Technologies, 1985-November 2005; English language, clinical trial), PubMed (1985-November 2005; English language, clinical trial, humans), and the Cochrane Collaboration using the terms selective COX-2 inhibitors and coxibs, as well as the various chemical names for specific coxib agents. Studies that compared a coxib with a nonselective NSAID and provided data concerning our outcomes of interest were included and categorized by the outcome variable, as well as by the specific coxib studied. RESULTS: The majority of the numerous studies that evaluated pain as an endpoint showed no difference between coxib and nonselective NSAID therapy. However, while limited, preliminary safety data regarding the effects of both classes on the upper and lower GI tract suggest coxib superiority. Although coxibs are associated with an increased risk of cardiovascular adverse events (CVEs) compared with placebo, this effect has not been conclusively shown compared with nonselective NSAIDs. Currently, coxib therapy is more expensive than combination therapy using a nonselective NSAID plus a PPI. CONCLUSIONS: Compared with combination therapy including a nonselective NSAID and PPI, coxibs provide equivalent pain control and may have a lower GI tract complication profile, but at an unknown increased risk of CVEs and a greater financial cost. Coxib therapy may be an appropriate treatment for chronic pain in select patients with higher risks of GI complications, lower risk of CVEs, and in whom greater cost is not a restraint. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment,Gastrointestinal Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Inst Technol, Boston, MA 02114 USA. RP Hur, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment,Gastrointestinal Unit, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 NR 64 TC 23 Z9 23 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUN PY 2006 VL 40 IS 6 BP 1052 EP 1063 DI 10.1345/aph.1G493 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 054IF UT WOS:000238369300007 PM 16720709 ER PT J AU Sabol, KE Echevarria, KL Lewis, JS AF Sabol, KE Echevarria, KL Lewis, JS TI Community-associated methicillin-resistant Staphylococcus aureus: New bug, old drugs SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE methicillin resistance; community-acquired; community associated; Panton-Valentine leukocidin; Staphylococcus aureus; mec ID PANTON-VALENTINE LEUKOCIDIN; SOFT-TISSUE INFECTIONS; OF-THE-LITERATURE; CIPROFLOXACIN RESISTANCE; TRIMETHOPRIM-SULFAMETHOXAZOLE; SKIN INFECTIONS; MINOCYCLINE; EMERGENCE; STRAINS; VANCOMYCIN AB OBJECTIVE: To discuss community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections and evaluate older antibiotics as suitable therapeutic treatment options. DATA SOURCES: Searches of MEDLINE, EMBASE, and the Cochrane Library (1966-May 2006) were performed using the key terms methicillin resistance, community-acquired, community associated, treatment, Staphylococcus aureus, mec, and Panton-Valentine leukocidin. STUDY SELECTION AND DATA EXTRACTION: All articles were critically evaluated and all relevant information was included in this review. DATA SYNTHESIS: There has been a documented shift of methicillin resistance occurring in staphylococcal infections manifested within the community. Infections caused by CA-MRSA possess unique characteristics including lack of hospital-associated risk factors, improved susceptibility patterns, distinct genotypes, faster doubling times, and additional toxins. Potential therapeutic options to treat these infections include trimethoprim/sulfamethoxazole (TMP/SMX), clindamycin, tetracyclines, fluoroquinolones, and new antimicrobials. CONCLUSIONS: CA-MRSA infections can be successfully treated with older, oral antibiotic agents including TMP/SMX, clindamycin, and tetracyclines. Fluoroquinolones and linezolid should be avoided as first-line agents. C1 Univ Texas, Hlth Syst, Serv Pharm, San Antonio, TX 78229 USA. Parkland Hlth & Hosp Syst, Dallas, TX USA. S Texas Vet Healthcare Syst, Serv Pharm, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Clin Pharm, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78285 USA. RP Lewis, JS (reprint author), Univ Texas, Hlth Syst, Serv Pharm, 4502 Med Dr, San Antonio, TX 78229 USA. EM James.Lewis@uhs-sa.com NR 82 TC 31 Z9 32 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUN PY 2006 VL 40 IS 6 BP 1125 EP 1133 DI 10.1345/aph.1G404 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 054IF UT WOS:000238369300016 PM 16735661 ER PT J AU Cadle, RM Mansouri, MD Darouiche, RO AF Cadle, RM Mansouri, MD Darouiche, RO TI Vancomycin-induced elevation of liver enzyme levels SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE bioavailability; liver enzymes; vancomycin ID ORAL VANCOMYCIN; CLOSTRIDIUM-DIFFICILE; SYSTEMIC ABSORPTION; TOXICITY; THERAPY; COLITIS; DIGOXIN AB OBJECTIVE: To report a case of oral vancomycin-induced elevation of liver enzyme levels. CASE SUMMARY: A 57-year-old man with multiple medical conditions requiring systemic antibiotic therapy developed numerous Clostridium difficile-associated enterocolitis episodes. The patient did not respond adequately to oral metronidazole, as evidenced by his continuing diarrhea. He was treated with oral vancomycin on 5 separate occasions (with doses from 125 to 500 mg/day), each of which resulted in significant elevations in alanine aminotransferase (to 371 U/L) and aspartate aminotransferase (to 203 U/L) levels. The elevations resolved on each occasion with discontinuation of vancomycin. DISCUSSION: Vancomycin, a glycopepticle antibiotic, has primary activity against gram-positive bacteria. Oral vancomycin can be used for the treatment of C. difficile-associated enterocolitis in patients who fail to respond to or are intolerant to metronidazole therapy. Oral vancomycin has very poor bioavailability and, as of May 4, 2006, has not been associated with hepatic toxicity. Inflammatory bowel disease processes can result in increased absorption of oral vancomycin. CONCLUSIONS: This is the first reported case of oral vancomycin-induced elevation of hepatic enzyme levels. Use of the Naranjo probability scale indicated that this was a probable adverse drug-associated event. C1 Michael E DeBakey Vet Affairs Med Ctr, Pharm Serv 119, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Houston, TX 77030 USA. RP Cadle, RM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Pharm Serv 119, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM cadle.richardmark@med.va.gov NR 16 TC 8 Z9 8 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUN PY 2006 VL 40 IS 6 BP 1186 EP 1189 DI 10.1345/aph.1G668 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 054IF UT WOS:000238369300028 PM 16720708 ER PT J AU Hutter, MM Kellogg, KC Ferguson, CM Abbott, WM Warshaw, AL AF Hutter, MM Kellogg, KC Ferguson, CM Abbott, WM Warshaw, AL TI The impact of the 80-hour resident workweek on surgical residents and attending surgeons SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 117th Annual Meeting of the Southern-Surgical-Association CY DEC, 2005 CL Hot Springs, VA SP So Surg Assoc ID BURNOUT; QUALITY; CARE; SATISFACTION; REDUCTION; PROGRAM; STRESS; RISK AB Objective: To assess the impact of the 80-hour resident workweek restrictions on surgical residents and attending surgeons. Summary Background Data: The ACGME mandated resident duty hour restrictions have required a major workforce restructuring. The impact of these changes needs to be critically evaluated for both the resident and attending surgeons, specifically with regards to the impact on motivation, job satisfaction, the quality of surgeon training, the quality of the surgeon's life, and the quality of patient care. Methods: Four prospective studies were performed at a single academic surgical program with data collected both before the necessary workforce restructuring and 1 year after, including: 1) time cards to assess changes in components of daily activity; 2) Web-based surveys using validated instruments to assess burnout and motivation to work; 3) structured, taped, one-on-one interviews with an external PhD investigator; and 4) statistical analyses of objective, quantitative data. Results: After the work-hour changes, surgical residents have decreased "burnout" scores, with significantly less "emotional exhaustion" (Maslach Burnout Inventory: 29.1 "high" vs. 23.1 "medium," P = 0.02). Residents have better quality of life both in and out of the hospital. They felt they got more sleep, have a lighter workload, and have increased motivation to work (Herzberg Motivation Dimensions). We found no measurable, statistically significant difference in the quality of patient care (NSQIP data). Resident training and education objectively were not statistically diminished (ACGME case logs, ABSITE scores). Attending surgeons perceived that their quality of their life inside and outside of the hospital was "somewhat worse" because of the work-hour changes, as they had anticipated. Many concerns were identified with regards to the professional development of future surgeons, including a change toward a shift-worker mentality that is not patient-focused, less continuity of care with a loss of critical information with each handoff, and a decrease in the patient/doctor relationship. Conclusion: Although the mandated restriction of resident duty hours has had no measurable impact on the quality of patient care and has led to improvements for the current quality of life of residents, there are many concerns with regards to the training of professional, responsible surgeons for the future. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ernest Amory Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. MIT, Alfred P Sloan Sch Management, Org Studies Grp, Boston, MA USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,ACC 335, Boston, MA 02114 USA. EM mhutter@partners.org NR 28 TC 204 Z9 206 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUN PY 2006 VL 243 IS 6 BP 864 EP 875 DI 10.1097/01.sla.0000220042.48310.66 PG 12 WC Surgery SC Surgery GA 048QW UT WOS:000237962600030 PM 16772790 ER PT J AU Tomlinson, JS Ko, CY AF Tomlinson, JS Ko, CY TI Patient satisfaction: An increasingly important measure of quality SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID CANCER; CARE C1 Univ Calif Los Angeles, Ctr Surg Outcomes & Qual, W Los Angeles VA Med Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, UCLA Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. RP Ko, CY (reprint author), Univ Calif Los Angeles, Ctr Surg Outcomes & Qual, W Los Angeles VA Med Ctr, 8-684 Factor Bldg,Box 951781, Los Angeles, CA 90095 USA. EM cko@mednet.ucla.edu NR 7 TC 12 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2006 VL 13 IS 6 BP 764 EP 765 DI 10.1245/ASO.2006.01.904 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 043AJ UT WOS:000237571400003 PM 16614874 ER PT J AU Wong, SL Morton, DL Thompson, JF Gershenwald, JE Leong, SPL Reintgen, DS Gutman, H Sabel, MS Carlson, GW McMasters, KM Tyler, DS Goydos, JS Eggermont, AMM Nieweg, OE Cosimi, AB Riker, AI Coit, DG AF Wong, SL Morton, DL Thompson, JF Gershenwald, JE Leong, SPL Reintgen, DS Gutman, H Sabel, MS Carlson, GW McMasters, KM Tyler, DS Goydos, JS Eggermont, AMM Nieweg, OE Cosimi, AB Riker, AI Coit, DG TI Melanoma patients with positive sentinel nodes who did not undergo completion lymphadenectomy: A multi-institutional study SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 58th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-06, 2005 CL Atlanta, GA SP Soc Surg Oncol DE melanoma; sentinel lymph node biopsy; completion lymphadenectomy; recurrence; survival ID EARLY-STAGE MELANOMA; EARLY RECURRENCE; II MELANOMA; BIOPSY; DISSECTION; PATTERNS; TRIAL AB Background: Completion lymph node dissection (CLND) is considered the standard of care in melanoma patients found to have sentinel lymph node (SLN) metastasis. However, the therapeutic utility of CLND is not known. The natural history of patients with positive SLNs who do not undergo CLND is undefined. This multi-institutional study was undertaken to characterize patterns of failure and survival rates in these patients and to compare results with those of positive-SLN patients who underwent CLND. Methods: Surgeons from 16 centers contributed data on 134 positive-SLN patients who did not undergo CLND. SLN biopsy was performed by using each institution's established protocols. Patients were followed up for recurrence and survival. Results: In this study population, the median age was 59 years, and 62% were male. The median tumor thickness was 2.6 mm, 77% of tumors had invasion to Clark level IV/V, and 33% of lesions were ulcerated. The primary melanoma was located on the extremities, trunk, and head/neck in 45%, 43%, and 12%, respectively. The median follow-up was 20 months. The median time to recurrence was 11 months. Nodal recurrence was a component of the first site of recurrence in 20 patients (15%). Nodal recurrence-free survival was statistically insignificantly worse than that seen in a contemporary cohort of patients who underwent CLND. Disease-specific survival for positive-SLN patients who did not undergo CLND was 80% at 36 months, which was not significantly different from that of patients who underwent CLND. Conclusions: This study underscores the importance of ongoing prospective randomized trials in determining the therapeutic value of CLND after positive SLN biopsy in melanoma patients. C1 Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. John Wayne Canc Inst, Dept Surg, Santa Monica, CA USA. Royal Prince Alfred Hosp, Sydney Melanoma Unit, Sydney, NSW, Australia. Univ Texas, MD Anderson Canc Ctr, Dept Surg, Houston, TX 77030 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Lakeland Reg Canc Ctr, Dept Surg, Lakeland, FL USA. Tel Aviv Univ, Sackler Sch Med, Dept Surg, IL-69978 Tel Aviv, Israel. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Emory Univ, Dept Surg, Atlanta, GA 30322 USA. Univ Louisville, Dept Surg, Louisville, KY 40292 USA. Duke Univ, Dept Surg, Durham, NC USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, New Brunswick, NJ 08903 USA. Erasmus Univ, Med Ctr, Dept Surg, Rotterdam, Netherlands. Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Surg, Amsterdam, Netherlands. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Dept Surg, Tampa, FL 33682 USA. RP Coit, DG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA. EM coitd@mskcc.org RI Sabel, Michael/A-7521-2009; Riker, Adam/A-6065-2011 NR 15 TC 80 Z9 83 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2006 VL 13 IS 6 BP 809 EP 816 DI 10.1245/ASO.2006.03.058 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 043AJ UT WOS:000237571400011 PM 16604476 ER PT J AU Gaissert, HA Lin, N Wain, JC Fankhauser, G Wright, CD Mathisen, DJ AF Gaissert, HA Lin, N Wain, JC Fankhauser, G Wright, CD Mathisen, DJ TI Transthoracic heller myotomy for esophageal achalasia: Analysis of long-term results SO ANNALS OF THORACIC SURGERY LA English DT Article ID COMPARING FORCEFUL DILATATION; FUNDOPLICATION; ESOPHAGOMYOTOMY; RESECTION AB Background. Swallowing deteriorates over time in some patients after transthoracic esophagomyotomy for achalasia. The causes of decline are poorly understood. Methods. We report a retrospective analysis of transthoracic esophagomyotomy for achalasia. Symptom relief, patient satisfaction, and late intervention were determined during short- and long-term follow-up. Predictors of long-term outcome were identified by logistic regression. Results. From 1962 to 1999, 64 patients underwent transthoracic esophagomyotomy. Five patients had repeat myotomy. Sigmoid esophagus was present in 12 (18%). Fundoplication was absent in 50 patients (myotomy only) and added in 15 (myotomy plus fundoplication). Follow-up was complete in 86% ( 56 of 65); mean follow-up was 154 months. Thirty-one patients (48%) were followed for more than 10 years. Short-term results were good to excellent in 91% (51 of 56) and long-term in 63% (33 of 52; p < 0.0005). Late peptic stricture occurred in 4 patients ( myotomy only, 2 of 38 [5%]; myotomy plus fundoplication, 2 of 14 [14%]). Fewer patients had reflux symptoms after fundoplication ( myotomy only, 16 of 38 [42%]; myotomy plus fundoplication, 4 of 14 [29%]), whereas late dysphagia was not reduced ( myotomy only, 13 of 38 [34%]; myotomy plus fundoplication, 5 of 14 [36%]). Two patients after myotomy plus fundoplication and 1 after myotomy only had esophagectomy. Early recurrence of symptoms predicted late poor outcome (p < 0.001), whereas sigmoid esophagus, fundoplication, or early postoperative reflux did not. Conclusions. Early good results after esophagomyotomy for achalasia deteriorate over time. Recurring dysphagia early after operation predicts late failure, while sigmoid esophagus does not. Fundoplication reduces reflux symptoms, but not late poor results. These data should be considered in the evaluation of newer, minimally invasive procedures. C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org OI Fankhauser, Grant/0000-0002-0664-999X NR 18 TC 10 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUN PY 2006 VL 81 IS 6 BP 2044 EP 2049 DI 10.1016/j.athoracsur.2006.01.039 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 049PD UT WOS:000238027600016 PM 16731127 ER PT J AU Bosso, JA Mauldin, PD AF Bosso, JA Mauldin, PD TI Using interrupted time series analysis to assess associations of fluoroquinolone formulary changes with susceptibility of gram-negative pathogens and isolation rates of methicillin-resistant Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FIBRONECTIN-BINDING PROTEINS; INTENSIVE-CARE UNITS; PSEUDOMONAS-AERUGINOSA; ANTIMICROBIAL RESISTANCE; ESCHERICHIA-COLI; CIPROFLOXACIN RESISTANCE; HOSPITALIZED-PATIENTS; ECONOMIC OUTCOMES; US HOSPITALS; ANTIBIOTIC-RESISTANCE AB The use of fluoroquinolones has been linked to increasing bacterial resistance and infection and/or colonization with already resistant pathogens both as a risk factor and based on volume of use. Changes in individual fluoroquinolones used in an institution may also be related to these clinical problems. Interrupted time series analysis, which allows for assessment of the associations of an outcome attributable to a specific event in time, was used to study the effect of changes in our hospital's fluoroquinolone formulary on fluoroquinolone susceptibility rates in select gram-negative pathogens and the methicillin-resistant Staphylococcus aureus (MRSA) isolation rate. Susceptibility rates to ciprofloxacin were considered for the period of 1993 through 2004, while the MRSA isolation rate was assessed from 1995 through 2004. Levofloxacin was added to the formulary in 1999, and gatifloxacin was substituted for levofloxacin in 2001. Statistically significant changes in the already declining rates of susceptibility of Pseudomonas aeruginosa (P, 0.042) and Escherichia coli (P, 0.004) to ciprofloxacin and in the already rising MRSA isolation rate (P, 0.001) were associated with the addition of levofloxacin to the formulary. Substitution of gatifloxacin for levofloxacin on the formulary was associated with reversals in the downward trend in E. coli susceptibility to ciprofloxacin and the upward trend in MRSA isolation rate. No associations were detected on susceptibility of Klebsiella pneumoniae or Proteus mirabilis to ciprofloxacin. These findings suggest that potential changes in susceptibility to fluoroquinolones and isolation of MRSA may vary by both drug and organism. C1 Med Univ S Carolina, Coll Pharm, Dept Pharm & Clin Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Coll Med, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Coll Pharm, Ctr Medicat Safety, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Bosso, JA (reprint author), Med Univ S Carolina, Coll Pharm, Dept Pharm & Clin Sci, POB 250140, Charleston, SC 29425 USA. EM bossoja@musc.edu NR 51 TC 26 Z9 28 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2006 VL 50 IS 6 BP 2106 EP 2112 DI 10.1128/AAC.01359-05 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 048FE UT WOS:000237932200028 PM 16723572 ER PT J AU De Leval, L Harris, NL Lampertz, S Herens, C AF De Leval, L Harris, NL Lampertz, S Herens, C TI T-cell/histiocyte-rich large B-cell lymphoma associated with a near-tetraploid karyotype and complex genetic abnormalities SO APMIS LA English DT Article DE T-cell; histiocyte-rich large B-cell lymphoma; cytogenetics; karyotype; chromosome ID DISTINCT CLINICOPATHOLOGICAL ENTITY; PREDOMINANT HODGKINS-DISEASE; DIFFERENTIAL-DIAGNOSIS AB Cytogenetic data for T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) are scarcely available. We report here a case of THRLBCL with a near-tetraploid karyotype and complex chromosomal aberrations, without rearrangement of BCL2 or BCL6, and characterized pathologically by a variegated morphologic appearance with areas resembling nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL). C1 CHU Sart Tilman, Dept Pathol, B-4000 Liege, Belgium. CHU Sart Tilman, Dept Genet, B-4000 Liege, Belgium. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Ctr Hosp Bois Abbaye, Dept Hematol, Seraing, Belgium. RP De Leval, L (reprint author), CHU Sart Tilman, Dept Pathol, B-4000 Liege, Belgium. EM L.deLeval@ulg.ac.be NR 13 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0903-4641 J9 APMIS JI APMIS PD JUN PY 2006 VL 114 IS 6 BP 474 EP 478 DI 10.1111/j.1600-0463.2006.apm_458.x PG 5 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 059PI UT WOS:000238744300011 PM 16856972 ER PT J AU Marci, CD Orr, SP AF Marci, Carl D. Orr, Scott P. TI The effect of emotional distance on psychophysiologic concordance and perceived empathy between patient and interviewer SO APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK LA English DT Article DE empathy; emotional distance; skin conductance; psychophysiology; gaze ID ELECTRODERMAL ACTIVITY; AUTONOMIC RESPONSES; DEPRESSIVE PATIENTS; HEART-RATE; PSYCHOTHERAPY; REPRESENTATION; COMMUNICATION; SATISFACTION; EXPERIENCES; COMPONENTS AB This preliminary study investigated the effect of emotional distance on psychophysiologic concordance and perceived empathy in a clinical population. Participants included 20 adult outpatients from a mental health clinic that underwent a brief semi-structured interview with a trained psychiatrist in either an emotionally neutral or an emotionally distant condition. Simultaneous skin conductance (SC) levels of the patient and interviewer were recorded and used to calculate a measure of psychophysiologic concordance. Interviewer gaze was rated by an independent observer and used as a proxy indicator of emotional distance. Observer ratings of interviewer gaze, SC concordance, and patient ratings of perceived interviewer empathy were significantly lower in the emotionally distant condition compared with the emotionally neutral condition (p < 0.05). Results suggest that increased emotional distance is associated with decreased psychophysiologic concordance and reduced subjective ratings of perceived empathy. The observed differences in psychophysiologic concordance support the use of this measure as a potential marker of empathy in a clinical population in an interview setting. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Vet Affairs Med Ctr, Manchester, NH USA. RP Marci, CD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Pk Man St,WACC 812, Boston, MA 02114 USA. EM cmarci@partners.org FU NIMH NIH HHS [F32 MH 072073-01] NR 59 TC 24 Z9 24 U1 1 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-0586 J9 APPL PSYCHOPHYS BIOF JI Appl. Psychophysiol. Biofeedback PD JUN PY 2006 VL 31 IS 2 BP 115 EP 128 DI 10.1007/s10484-006-9008-4 PG 14 WC Psychology, Clinical SC Psychology GA 078SD UT WOS:000240122700003 PM 16724278 ER PT J AU Gupta, SG Wang, LC Penas, PF Gellenthin, M Lee, SJ Nghiem, P AF Gupta, SG Wang, LC Penas, PF Gellenthin, M Lee, SJ Nghiem, P TI Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma - The Dana-Farber experience and meta-analysis of the literature SO ARCHIVES OF DERMATOLOGY LA English DT Article ID CASE SERIES; MELANOMA; SKIN; RADIOLOCALIZATION; LYMPHADENECTOMY; LYMPHONODECTOMY; METASTASES; RECIPIENTS AB Objective: To determine the diagnostic accuracy and usefulness of sentinel lymph node biopsy (SLNB) and computed tomographic scans in the initial evaluation and treatment of patients with Merkel cell carcinoma (MCC). Design: Single-institution case series and literature based case-level meta-analysis. Setting: Academic cutaneous oncology clinic. Patients: Sixty-one adults with biopsy-proven MCC (30 who had undergone SLNB) plus 92 cases from the literature of patients who had undergone SLNB. Main Outcome Measures: Relapse-free survival Results: In 122 patients with no nodal disease found by physical examination, SLNB findings revealed nodal involvement in 39 cases (32%). At 3 years, the recurrence rate for those with a positive SLNB was 3 times (60%) higher than for those with a negative SLNB (20%; P =.03). Patients with a positive SLNB who received adjuvant nodal therapy had a relapse-free survival rate of 51% at 3 years (n = 26) compared with 0% for patients who did not receive nodal therapy (n = 3; P<.01). In contrast, among patients with a negative SLNB there was no significant difference in 3-year relapse-free survival rates for those who did (90%; n = 24) or did not (70%; n = 19; P =. 26) receive adjuvant nodal therapy. Using SLNB plus clinical follow-up as a gold standard, computed tomographic scans had low sensitivity (20%) for detecting MCC that had spread to the lymph node basin and low specificity for distant disease (only 4 of 21 "positive" scans were confirmed during 6 months of follow-up). Conclusions: Sentinel lymph node biopsy detects MCC spread in one third of patients whose tumors would have otherwise been clinically and radiologically understaged and who may not have received treatment to the involved node bed. There was a significant benefit of adjuvant nodal therapy, but only when the SLNB was positive. Thus, SLNB is important for both prognosis and therapy and should be performed routinely for patients with MCC. In contrast, computed tomographic scans have poor sensitivity in detecting nodal disease as well as poor specificity in detecting distant disease. C1 Dana Farber Brigham & Womens Canc Ctr, Cutaneous Oncol Dis Ctr, Boston, MA USA. Dana Farber Brigham & Womens Canc Ctr, Ctr Outcomes & Policy Res, Boston, MA USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Hosp Univ Princesa, Dept Dermatol, Madrid, Spain. Charite Univ Med, Dept Dermatol, Allergy & Skin Canc Ctr, Berlin, Germany. RP Nghiem, P (reprint author), Seattle Canc Care Alliance, 825 Eastlake Ave E,Box 358050, Seattle, WA 98195 USA. EM pnghiem@u.washington.edu RI Nghiem, Paul/A-9210-2011; Fernandez-Penas, Pablo/B-3948-2008 OI Nghiem, Paul/0000-0003-2784-963X; Fernandez-Penas, Pablo/0000-0003-4882-1564 NR 30 TC 182 Z9 184 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2006 VL 142 IS 6 BP 685 EP 690 DI 10.1001/archderm.142.6.685 PG 6 WC Dermatology SC Dermatology GA 053EX UT WOS:000238289500003 PM 16785370 ER PT J AU Kessler, RC Coccaro, EF Fava, M Jaeger, S Jin, R Walters, E AF Kessler, RC Coccaro, EF Fava, M Jaeger, S Jin, R Walters, E TI The prevalence and correlates of DSM-IV intermittent explosive disorder in the national comorbidity survey replication SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID WORLD-HEALTH-ORGANIZATION; MAJOR DEPRESSIVE DISORDER; NCS-R; AGGRESSIVE-BEHAVIOR; ANGER ATTACKS; UNITED-STATES; LIFETIME; OUTPATIENTS; DIAGNOSES; CRITERIA AB Context: Little is known about the epidemiology of intermittent explosive disorder (IED). Objective: To present nationally representative data on the prevalence and correlates of DSM-IV IED. Design: The World Health Organization Composite International Diagnostic Interview was used to assess DSM-IV anxiety disorders, mood disorders, substance use disorders, and impulse control disorders. Setting: The National Comorbidity Survey Replication, a face-to-face household survey carried out in 2001-2003. Participants: A nationally representative sample of 9282 people 18 years and older. Main Outcome Measure: Diagnoses of DSM-IV IED. Results: Lifetime and 12-month prevalence estimates of DSM-IV IED were 7.3% and 3.9%, with a mean 43 lifetime attacks resulting in $1359 in property damage. Intermittent explosive disorder-related injuries occurred 180 times per 100 lifetime cases. Mean age at onset was 14 years. Sociodemographic correlates were uniformly weak. Intermittent explosive disorder was significantly comorbid with most DSM-IV mood, anxiety, and substance disorders. Although the majority of people with IED (60.3%) obtained professional treatment for emotional or substance problems at some time in their life, only 28.8% ever received treatment for their anger, while only 11.7% of 12-month cases received treatment for their anger in the 12 months before interview. Conclusions: Intermittent explosive disorder is a much more common condition than previously recognized. The early age at onset, significant associations with comorbid mental disorders that have later ages at onset, and low proportion of cases in treatment all make IED a promising target for early detection, outreach, and treatment. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Univ Chicago, Pritzker Sch Med, Dept Psychiat, Clin Neurosci & Psychopharmacol Res Unit, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM kessler@hcp.med.harvard.edu FU FIC NIH HHS [R03 TW006481, R03 TW006481-02S1]; NIDA NIH HHS [R01 DA016558-02, R01 DA016558]; NIMH NIH HHS [R01 MH069864, R01 MH069864-02, R01 MH070884, R01 MH070884-01A2, R13 MH066849, R13 MH066849-03, U01 MH060220, U01 MH060220-05, U01-MH60220, U13 MH066849] NR 43 TC 155 Z9 156 U1 4 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 2006 VL 63 IS 6 BP 669 EP 678 DI 10.1001/archpsyc.63.6.669 PG 10 WC Psychiatry SC Psychiatry GA 049XD UT WOS:000238050200009 PM 16754840 ER PT J AU Sun, M Latourelle, JC Wooten, F Lew, MF Klein, C Shill, HA Golbe, LI Mark, MH Racette, BA Perlmutter, JS Parsian, A Guttman, M Nicholson, G Xu, G Wilk, JB Saint-Hilaire, MH DeStefano, AL Prakash, R Williamson, S Suchowersky, O Labelle, N Growdon, JH Singer, C Watts, RL Goldwurm, S Pezzoli, G Baker, KB Pramstaller, PP Burn, DJ Chinnery, PF Sherman, S Vieregge, P Litvan, I Gillis, T MacDonald, ME Myers, RH Gusella, JF AF Sun, M Latourelle, JC Wooten, F Lew, MF Klein, C Shill, HA Golbe, LI Mark, MH Racette, BA Perlmutter, JS Parsian, A Guttman, M Nicholson, G Xu, G Wilk, JB Saint-Hilaire, MH DeStefano, AL Prakash, R Williamson, S Suchowersky, O Labelle, N Growdon, JH Singer, C Watts, RL Goldwurm, S Pezzoli, G Baker, KB Pramstaller, PP Burn, DJ Chinnery, PF Sherman, S Vieregge, P Litvan, I Gillis, T MacDonald, ME Myers, RH Gusella, JF TI Influence of heterozygosity for Parkin mutation on onset age in familial Parkinson disease The GenePD study SO ARCHIVES OF NEUROLOGY LA English DT Article ID RECESSIVE JUVENILE PARKINSONISM; PSEUDO-DOMINANT INHERITANCE; HOMOZYGOUS DELETIONS; TRIPLICATION; ALLELES AB Background: The PARK2 gene at 6q26 encodes parkin, whose inactivation is implicated in an early-onset autosomal recessive form of Parkinson disease (PD). Objective: To evaluate the influence of heterozygosity for parkin mutation on onset age in a sample of families with at least 2 PD-affected members. Design: Clinical and genetic study. Setting: Twenty collaborative clinical sites. Patients: Patients with familial PD collected in the GenePD study. Studied families were selected for (1) affected sibling pairs sharing 2 alleles identical by state at PARK2 (D6S305) or (2) 1 or more family members with onset age younger than 54 years, regardless of D6S305 status. At least 1 member from each of 183 families underwent comprehensive screening for deletion/insertion variants and point mutations in PARK2. Main Outcome Measures: Mutations in the parkin gene were screened by means of single-stranded conformation polymorphism and sequencing in all 12 coding exons and flanking intronic sequences for point mutations and duplex quantitative polymerase chain reaction in all exons for rearrangement, duplication, and deletion. Results: Mutations were found in 23 families (12.6% of those screened). Among the mutation-positive families, 10 (43%) contained compound heterozygotes; 3 (13%), homozygotes; and 10 (43%), heterozygotes. The onset age in patients with parkin gene mutations ranged from 20 to 76 years. Patients with 1 parkin mutation had an 11.7-year age at onset than did patients with none (P=.04), and patients with 2 or more parkin mutations had a 13.2-year decrease in age at onset compared with patients with 1 mutation (P=.04). Conclusions: These data indicate that parkin mutations are not rare in multiply affected sibships, and that heterozygous mutation carrier status in PARK2 significantly influences age at onset of PD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Neurogenet Unit, Ctr Human Genet Res,Richard B Simches Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Univ Virginia, Dept Neurol, Hlth Syst, Charlottesville, VA USA. Univ So Calif, Los Angeles, CA USA. Med Univ Lubeck, D-23538 Lubeck, Germany. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Sydney, Concord Hosp, Mol Med Lab, Sydney, NSW 2006, Australia. Univ Miami, Miami, FL 33152 USA. Univ Alabama, Birmingham, AL USA. Gen Reg Hosp Bolzano, Bolzano, Italy. Univ Arizona, Tucson, AZ USA. Univ Louisville, Sch Med, Louisville, KY 40292 USA. Barrow Neurol Inst, Muhammad Ali Parkinson Res Ctr, Phoenix, AZ 85013 USA. Univ Arkansas Med Sci, Dept Pediat, Human Genom Labs, Little Rock, AR 72205 USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. Univ Calgary, Dept Med Genet, Calgary, AB, Canada. Parkinson Inst, Ist Clin Perfezionamento, Milan, Italy. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA. Newcastle Gen Hosp, Reg Neurosci Ctr, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Klinikum Lippe Lemgo, Neurol Klin, Lemgo, Germany. RP Gusella, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Neurogenet Unit, Ctr Human Genet Res,Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu RI Pramstaller, Peter/C-2357-2008; Goldwurm, Stefano/Q-8978-2016; OI Goldwurm, Stefano/0000-0002-1651-567X; Litvan, Irene/0000-0002-3485-3445 FU NIGMS NIH HHS [T32GM007748]; NINDS NIH HHS [R01 NS36711]; Telethon [GTF04007] NR 33 TC 89 Z9 91 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2006 VL 63 IS 6 BP 826 EP 832 DI 10.1001/archneur.63.6.826 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 051YM UT WOS:000238197600005 PM 16769863 ER PT J AU Costello, DJ Simon, MV Eskandar, EN Frosch, MP Henninger, HL Chiappa, KH Cole, AJ AF Costello, DJ Simon, MV Eskandar, EN Frosch, MP Henninger, HL Chiappa, KH Cole, AJ TI Efficacy of surgical treatment of de Novo, adult-onset, cryptogenic, refractory focal status epilepticus SO ARCHIVES OF NEUROLOGY LA English DT Article ID NEUROSURGICAL TREATMENT; CORTICAL DYSPLASIA; MORBIDITY; PROGNOSIS; MORTALITY; SURGERY AB Background: There have been few published reports of successful surgical treatment of focal status epilepticus. Surgical intervention is considered a last resort after medical strategies have been exhausted. Objective: To report a case of an adult who was initially seen with de novo, medically refractory, cryptogenic focal status epilepticus and underwent resection of an electrographically defined portion of the left middle frontal gyrus with multiple subpial transections of the adjacent cortex resulting in termination of the electroclinical seizure activity. Design: Report of a case of successful surgical treatment of cryptogenic focal status epilepticus. Intervention: After an initial 35 days of oral antiepileptic drug therapy and subsequent 16 days of continuous electroencephalography-guided intravenous antiepileptic drug therapy in an intensive care unit setting, and after extensive preoperative and intraoperative characterization of the epileptogenic zone, a tailored resection of the left middle frontal gyrus with multiple subpial transections of the surrounding cortex was performed. Results: The restricted surgical resection and multiple subpial transections terminated the seizure activity. Neuropathological examination of the resected tissue revealed moderate inflammatory changes and a few abnormally located neurons without any definitive evidence of dysplasia, which was suspected preoperatively. Conclusions: We suggest that focal cortical resection may be an appropriate intervention in medically refractory focal status epilepticus even when an overt structural etiology is not evident preoperatively and should be considered as an option at the onset of intractability. C1 Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Maine Med Ctr, Dept Neurol, Portland, OR USA. RP Costello, DJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, 55 Fruit St, Boston, MA 02114 USA. EM djcostello@partners.org NR 15 TC 19 Z9 19 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2006 VL 63 IS 6 BP 895 EP 901 DI 10.1001/archneur.63.6.895 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 051YM UT WOS:000238197600016 PM 16769873 ER PT J AU Lister, MT Cunningham, MJ Benjamin, B Williams, M Tirrell, A Schaumberg, DA Hartnick, CJ AF Lister, MT Cunningham, MJ Benjamin, B Williams, M Tirrell, A Schaumberg, DA Hartnick, CJ TI Microdebrider tonsillotomy vs electrosurgical tonsillectomy SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Preventive-Oncology CY MAY 28, 2005 CL Las Vegas, NV SP Amer Soc Prevent Ocol ID CHILDREN; PAIN; HYPERTROPHY AB Objective: To examine whether microdebrider intracapsular tonsillotomy (MT) results in less postoperative pain compared with electrosurgical extracapsular tonsillectomy (ET). Design: Prospective, randomized, double-blind, matched pair, clinical trial. Setting: Specialty care hospital. Patients: Twelve male (48%) and 13 female (52%) children aged 5 to 15 years, with obstructive tonsillar hyperplasia were randomized to have one tonsil removed by MT and the other by ET. Interventions: An angled endoscopic microdebrider was used to perform MT, and ET was performed by standard monopolar cautery technique. Parents and children were blinded to the side of MT and ET. Children rated the pain 0 to 5 by side using the Faces Pain Scale-Revised. Blinded data collection was via telephone daily for 2 weeks by a study nurse. Main Outcome Measures: Primary: postoperative pain as recorded by Faces Pain Scale-Revised; secondary, presence or absence of otalgia and postoperative bleeding. Results: Twenty-two children (88%) had tonsillectomy and adenoidectomy, while 3 children (12%) had tonsillectomy alone. On postoperative days 1 to 9, children reported significantly less pain on the MT side compared with the ET side (paired t test; P <.01). By postoperative days 10 to 14, the difference between sides disappeared. Twenty children (80%) reported otalgia, and it was always unilateral. For those children reporting otalgia, there was a 100% correlation between the side of otalgia and the side of ET. There was no posttonsillectomy bleeding among the 25 children. Conclusion: Microdebrider intracapsular tonsillotomy is significantly less painful compared with electrosurgical ET in children undergoing surgical intervention for obstructive tonsillar hypertrophy. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Hartnick, CJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 15 TC 47 Z9 48 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 2006 VL 132 IS 6 BP 599 EP 604 DI 10.1001/archotol.132.6.599 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 052VF UT WOS:000238261300005 PM 16785404 ER PT J AU Haddad, R Tishler, R Wirth, L Norris, CM Goguen, L Sullivan, C O'Donnell, L Li, Y Posner, M AF Haddad, R Tishler, R Wirth, L Norris, CM Goguen, L Sullivan, C O'Donnell, L Li, Y Posner, M TI Rate of pathologic complete responses to docetaxel, cisplatin, and fluorouracil induction chemotherapy in patients with squamous cell carcinoma of the head and neck SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID ADVANCED LARYNGEAL-CANCER; PHASE-III TRIAL; OROPHARYNGEAL CARCINOMA; ORGAN PRESERVATION; ACTIVE-DRUG; CHEMORADIATION; THERAPY; CHEMORADIOTHERAPY; RADIOTHERAPY; PACLITAXEL AB Objective: To report the rate of pathological complete response after induction chemotherapy with the docetaxel, cisplatin, and fluorouracil (TPF) combination. Design: Retrospective cohort analysis. Setting: Tertiary care academic cancer center, between June 1999 and May 2004. Patients: Seventy-two patients with newly diagnosed squamous cell carcinoma of the head and neck; 68 (95%) of the patients had stage IV, locally advanced disease. Interventions: Three cycles of induction chemotherapy followed by a biopsy of the primary site. All patients subsequently underwent chemotherapy with 3 cycles of TPF. Main Outcome Measure: Rate of pathological complete response at the primary site after induction chemotherapy with 3 cycles of TPF. Results: Biopsy results were negative for cancer in 64 patients (89%) and positive in 8 patients (11%). The median follow-up was 2 years. In the positive biopsy result group, 2 (25%) of 8 patients died of disease vs 3 (4%) of 64 patients in the negative biopsy result group. Twenty-nine neck dissections were performed; results were positive in 7 patients (all alive with no evidence of disease) and negative in 22 patients (21 alive with no evidence of disease). The overall 2- and 5-year progression-free survival is currently projected at 85% and 85%, respectively; the overall 2- and 5-year survival, at 95% and 90%, respectively. Importantly, T4 presentation did not predict a positive biopsy result at the primary site or a positive neck dissection result (P = .60 and P = .56, respectively). N3 presentation (12 patients) did not predict a positive biopsy result at the primary site (P = .87) but did correlate with positive neck dissection results in 6 of 12 patients (P < .001). Conclusions: Induction chemotherapy with the TPF regimen results in a high pathological complete response rate (89%). This rate is higher than with the cisplatin plus fluorouracil combination therapy, which was reported to be between 25% and 50% in previous studies. Chemoradiotherapy is currently an accepted standard of care, but induction chemotherapy continues to be investigated. Based on recent phase 3 trial results and the data presented herein, we propose that the 3-drug combination be used as the new platform when administering induction chemotherapy. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Otolaryngol, Boston, MA 02115 USA. Wake Forest Univ Hlth Sci, Dept Otolaryngol, Winston Salem, NC USA. RP Haddad, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Shields Warren Bldg,Room 430G,44 Binney St, Boston, MA 02115 USA. EM Robert_haddad@dfci.harvard.edu NR 23 TC 14 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUN PY 2006 VL 132 IS 6 BP 678 EP 681 DI 10.1001/archotol.132.6.678 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 052VF UT WOS:000238261300016 PM 16785415 ER PT J AU Matuskova, J Chauhan, AK Cambien, B Astrof, S Dole, VS Piffath, CL Hynes, RO Wagner, DD AF Matuskova, J Chauhan, AK Cambien, B Astrof, S Dole, VS Piffath, CL Hynes, RO Wagner, DD TI Decreased plasma fibronectin leads to delayed thrombus growth in injured arterioles SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE plasma fibronectin; arterial and venous injury; thrombus; fibronectin splice variants; intravital microscopy ID ALTERNATIVELY SPLICED EIIIB; ISOFORM DISTRIBUTION; MICE LACKING; V-SEGMENT; MOUSE; SURFACES; PROMOTES; ADHESION; COLLAGEN; HEMOSTASIS AB Objective - Plasma fibronectin (FN) is decreased in several clinical conditions. We were interested to study the thrombotic and hemostatic consequences of the decrease in plasma FN (pFN), the role of FN splice variants in thrombosis, and to examine whether pFN incorporates into thrombi in vivo. Methods and Results - We compared the thrombotic response to a vessel injury in FN heterozygous (FN-/-) mice and corresponding FN-/- mice. Although normal thrombosis in venules was observed, a decrease to half in the pFN concentration in FN-/- mice caused a delay in the appearance of thrombi in arterioles and consequently a delay in their occlusion. We were able to rescue the thrombotic defect in the FN-/- mice by infusion of rat pFN. Additionally, we could show intense incorporation of fluorescent pFN-coated microspheres into the developing thrombi. Moreover, we found that mice expressing FN without the EIIIA or EIIIB domains specific to cellular FN including platelet FN had no thrombotic defect. Conclusions - Mice heterozygous for FN have a striking defect in thrombus initiation and growth in arterioles attributable to the decrease of pFN. Our study is an example of haploid insufficiency for FN, and it emphasizes the fundamental role of this plasma protein in thrombosis in the arterial system. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Ctr Canc Res, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu OI Astrof, Sophie/0000-0001-9338-9083 FU NHLBI NIH HHS [P01 HL066105, R37 HL 41002, R01 HL041002] NR 31 TC 40 Z9 42 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2006 VL 26 IS 6 BP 1391 EP 1396 DI 10.1161/01.ATV.0000216282.58291.c6 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 044AI UT WOS:000237644000032 PM 16528004 ER PT J AU Kathiresan, S Yang, Q Larson, MG Camargo, AL Tofler, GH Hirschhorn, JN Gabriel, SB O'Donnell, CJ AF Kathiresan, S Yang, Q Larson, MG Camargo, AL Tofler, GH Hirschhorn, JN Gabriel, SB O'Donnell, CJ TI Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE coagulation; fibrinogen; genetics; myocardial infarction; plasminogen activators; thrombosis; polymorphism ID CORONARY-HEART-DISEASE; PLASMINOGEN-ACTIVATOR GENE; ENHANCER POLYMORPHISM; HUMAN GENOME; RETINOIC ACID; ASSOCIATION; FIBRINOGEN; IDENTIFICATION; PROMOTER; REGION AB Objective - We undertook a linkage disequilibrium (LD) - based genetic approach to investigate the hypothesis that common sequence variants in 5 thrombosis genes influence plasma hemostatic protein levels or risk of cardiovascular disease (CVD). Methods and Results - In a reference panel, we characterized LD structure at the fibrinogen gene cluster (fibrinogen-beta[FGB], FGA, and FGG), factor VII (F7), and tissue plasminogen activator (PLAT) loci. Forty-one tag single nucleotide polymorphisms (SNPs) were genotyped in 1811 unrelated Framingham Heart Study participants. There were significant associations of 9 FGB SNPs with fibrinogen level (minimum P = 0.002) and of 7 F7 SNPs and factor VII level (minimum P < 0.0001). SNPs at the PLAT locus were not associated with PLAT level. In stepwise analysis, a single FGB variant explained 1% of the residual variance in fibrinogen level, and 2 F7 SNPs together explained 10% of the residual variance in factor VII level. Two PLAT haplotypes were associated with CVD (multivariable-adjusted global P = 0.0004). Conclusions - A comprehensive survey of common sequence variation demonstrates that cis-regulatory SNPs explain a modest proportion of the residual variance in circulating fibrinogen and factor VII level and PLAT haplotypes increase the risk of CVD. Additional studies are warranted to confirm the association of PLAT sequence variation and risk of CVD. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Royal N Shore Hosp, Sydney, NSW, Australia. Harvard Univ, Sch Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Endocrinol, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov RI Yang, Qiong/G-5438-2014; OI Larson, Martin/0000-0002-9631-1254 FU NHLBI NIH HHS [HL66582, N01-HC-25195] NR 39 TC 45 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2006 VL 26 IS 6 BP 1405 EP 1412 DI 10.1161/01.ATV.0000222011.13026.25 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 044AI UT WOS:000237644000034 PM 16614319 ER PT J AU Bowman, TS Kurth, T Sesso, HD Gaziano, JM AF Bowman, T. S. Kurth, T. Sesso, H. D. Gaziano, J. M. TI A prospective study of change in BMI and risk ofcardiovascular disease in men SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 66 EP 66 DI 10.1016/S1567-5688(06)80228-X PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093900229 ER PT J AU Deitiker, PR Oshima, M Smith, RG Mosier, DR Atassi, MZ AF Deitiker, Philip R. Oshima, Minako Smith, R. Glenn Mosier, Dennis R. Atassi, M. Zouhair TI Subtle differences in HLA DQ haplotype-associated presentation of AChR alpha-chain peptides may suffice to mediate myasthenia gravis SO AUTOIMMUNITY LA English DT Article DE acetylcholine receptor; autoimmunity; HLA; myasthenia gravis; T-cell ID HUMAN ACETYLCHOLINE-RECEPTOR; T-CELL RECOGNITION; PERIPHERAL-BLOOD LYMPHOCYTES; IN-VITRO; EXTRACELLULAR PART; ANTIBODY; SUBUNIT; DISEASE; SUSCEPTIBILITY; IDENTIFICATION AB The HLA DQA1 and DQB1 alleles were determined on a set of 24 myasthenia gravis patients that had previously been examined for their T-cell proliferative responses to the 18 overlapping peptides representing the extracellular domain of h AChR alpha-chain. Patient responses according to assumed cis or trans haplotypes were significantly higher in most cases relative to normal controls. Comparisons of in vitro peptide-stimulated T-cell responses of patient pairs which had DQA1:DQB1 in common displayed responses in tighter distribution relative to comparisons in which patient pairs did not share the same DQA1:DQB1 haplotype. Similar haplotypes, such as DQA1*0102:DQB1*0602 and DQA1*0102:DQB1*0604, tended to exhibit similar responses and were grouped according to this similarity. Modified F -test and Student's T -test analyses on DQ isoform bearing groups revealed that high responses to peptide alpha 34-49 were associated with A1*0102:B1*0602/0604, A1*0301:B1*0302 and A1*0401/0303:B1*0301. Peptide alpha 146-162 showed higher responses in A1*0301:B1*0302 group and moderate responses in A1*0401/0303:B1*0301 groups. Differences in the age of disease onset relative to DQ haplotypes were also observed. Groups of A1*0301:B1*0302, A1*0501:B1*0201 and A1*0102:B1*0604 showed earlier ages of disease onset relative to those of A1*0102:B1*0602 or A1*0505:B1*0301. C1 Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA. Univ Texas, Med Branch, Dept Neurol, Galveston, TX 77555 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. ME DeBakey VA Med Ctr, Neurol & Med Res Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. RP Oshima, M (reprint author), Baylor Coll Med, Dept Biochem & Mol Biol, 1 Baylor Pl, Houston, TX 77030 USA. EM moshima@bcm.tmc.edu NR 38 TC 9 Z9 11 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PD JUN PY 2006 VL 39 IS 4 BP 277 EP 288 DI 10.1080/08916930600738581 PG 12 WC Immunology SC Immunology GA 070ZS UT WOS:000239566900003 PM 16891216 ER PT J AU Weindruch, R AF Weindruch, Richard TI Will dietary restriction work in primates? SO BIOGERONTOLOGY LA English DT Editorial Material DE dietary restriction; aging; primates ID PROSTATE-CANCER RISK; CALORIC RESTRICTION; HUMANS; LONGEVITY; ENERGY; SWEDEN AB This issue of Biogerontology addresses whether dietary restriction (DR) "... can increase longevity in all species, particularly in human beings." The possibility that DR can increase longevity in all species seems a trivial issue compared to that of DR's potential efficacy in people. The striking phylogenetic breadth of DR's longevity increasing effect supports the notion of human translatability. The available evidence in primates (human and nonhuman) suggests that it is highly probable that DR will increase the span of good health (and the average lifespan) but the magnitude of this predicted increase is unknown. Robust survival data for monkeys subjected to highly controlled DR will be available in similar to 25 years; similar data for large numbers of human practitioners of DR appear to be many decades away. C1 Univ Wisconsin, Dept Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. RP Weindruch, R (reprint author), Univ Wisconsin, Dept Med, Madison, WI 53705 USA. EM rhweindr@wisc.edu NR 14 TC 12 Z9 12 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1389-5729 J9 BIOGERONTOLOGY JI Biogerontology PD JUN PY 2006 VL 7 IS 3 BP 169 EP 171 DI 10.1007/s10522-006-9007-0 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 085AY UT WOS:000240576700011 PM 16680522 ER PT J AU Fava, M McCall, WV Krystal, A Wessel, T Rubens, R Caron, J Amato, D Roth, T AF Fava, M McCall, WV Krystal, A Wessel, T Rubens, R Caron, J Amato, D Roth, T TI Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE insomnia; major depressive disorder; comorbidity; adjunctive antidepressant therapy; antidepressant remission rates; eszopiclone ID DOUBLE-BLIND; RECURRENT DEPRESSION; SLEEP DISTURBANCE; EFFICACY; CLONAZEPAM; SYMPTOMS; SAFETY; COTHERAPY; ZOLPIDEM; THERAPY AB Background. Insomnia and major depressive disorder (MDD) can coexist. This study evaluated the effect of adding eszopiclone to fluoxetine. Methods: Patients who met DSM-IV criteria for both MDD and insomnia (n = 545) received morning fluoxetine and were randomized to nightly eszopiclone 3 mg (ESZ+FLX) or placebo (PBO+FLX)for 8 weeks. Subjective sleep and daytime function were assessed weekly. Depression was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-I) and Severity items (CGI-S). Results: Patients in the ESZ+FLX group bad significantly decreased sleep latency, wake time after sleep onset (WASO), increased total sleep time (TST), sleep quality, and depth of sleep at all double-blind time points (all p < .05). Eszopiclone co-therapy also resulted in: significantly greater changes in HAM-D-17 scores at Week 4 (p = .01) with progressive improvement at Week 8 (p = .002); significantly improved CGI-I and CGI-S scores at all time points beyond Week 1 (p < .05); and significantly more responders (59% vs. 48%'; p = .009) and remitters (42% vs. 33%; p = .03) at Week 8. Treatment was well tolerated, with similar adverse event and dropout rates. Conclusions: In this study, eszopiclone/fluoxetine co-therapy was relatively well tolerated and associated with rapid, substantial, and sustained sleep improvement, a faster onset of antidepressant response on the basis of CGI, and a greater magnitude of the antidepressant effect. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Sepracor, Marlborough, MA USA. Wake Forest Univ, Dept Psychiat & Behav Sci, Winston Salem, NC 27109 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. Henry Ford Hosp, Sleep Ctr, Detroit, MI 48202 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 50 Staniford St,4th Floor, Boston, MA 02114 USA. EM mfava@partners.org RI Krystal, Andrew/J-7109-2013 OI Krystal, Andrew/0000-0002-6702-781X NR 33 TC 228 Z9 235 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2006 VL 59 IS 11 BP 1052 EP 1060 DI 10.1016/j.biopsych.2006.01.016 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 054ZB UT WOS:000238416000010 PM 16581036 ER PT J AU Wilens, TE Verlinden, MH Adler, LA Wozniak, PJ West, SA AF Wilens, TE Verlinden, MH Adler, LA Wozniak, PJ West, SA TI ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: Results of a pilot study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE adult; ADHD; nicotinic receptor agonist; treatment; pilot study; pharmacology ID DEFICIT HYPERACTIVITY DISORDER; COGNITIVE PERFORMANCE; ADHD; DEFINITION; IMPACT AB Background: This pilot study was designed to evaluate ABT-089, a neuronal nicotinic receptor partial agonist, as treatment for adult attention-deficit/hyperactivity disorder (ADHD). Methods: Adults with ADHD received placebo, 2 mg, 4 mg, or 20 mg of ABT-089 for 2 weeks each in a randomized, double-blind, placebo-controlled. 4 x 4 Latin square design for a total of 8 weeks. In addition to the primary outcome, the Conners Adult ADHD Rating Scale (CAARS), secondary rating scales, and neuropsychological and safety assessments were completed. Results: A total of 11 adults with well-characterized ADHD completed this crossover study. ABT-089 b.i.d. was superior to placebo for the CAARS Total Symptom Score, which was the primary endpoint (placebo: 38.0 +/- 1.9; 2 mg b.i.d.: 32.2 +/- 1.9, one-tail p = .021; 4 mg b.i.d.: 33.2 +/- 1.9, p = .047; 20 mg b.i.d.: 33.5 +/- 1.9, p = .056). ABT-089 was also superior to placebo for the CAARS ADHD Index and Hyperactive/Impulsive scores and the Clinical Global Impression-ADHD Severity score. On the clinical efficacy endpoints, CAARS Total Symptom Score and CAARS Hyperactive/Impulsive score, a shallow inverted U-shaped dose-response curve was observed; however. the dose-response curve for attention and memory effects as measured by computerized cognitive testing seemed dose-linear. No clinically meaningful findings in safety assessments or side effect profile were observed effective in treating adult ADHD and that it is well tolerated. Conclusions: Data from this pilot study suggest that ABT-089 might be effective in treating adult ADHD and that it is well tolerated. On the basis of these promising results, larger, parallel-group ABT-089 studies of longer duration are warranted. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Yawkey Ctr Outpatient Care YAW 6A, Dept Psychiat, Boston, MA 02114 USA. Abbott, Abbott Pk, IL USA. NYU, Sch Med, Combined Psychiat & Neurol Adult ADHD Program, New York, NY USA. New York Vet Affairs Harbor Healthcare Syst, Psychiat Serv, New York, NY USA. CNS Healthcare, Orlando, FL USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Yawkey Ctr Outpatient Care YAW 6A, Dept Psychiat, 32 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org OI Adler, Len/0000-0002-9812-8234 NR 32 TC 85 Z9 87 U1 0 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 JUN 1 PY 2006 VL 59 IS 11 BP 1065 EP 1070 DI 10.1016/j.biopsych.2005.10.029 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 054ZB UT WOS:000238416000012 PM 16499880 ER PT J AU Joffe, H Cohen, LS Suppes, T McLaughlin, WL Lavori, P Adams, JM Hwang, CH Hall, JE Sachs, GS AF Joffe, H Cohen, LS Suppes, T McLaughlin, WL Lavori, P Adams, JM Hwang, CH Hall, JE Sachs, GS TI Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; women; polycystic ovarian syndrome; valproate; adverse events ID POLYCYSTIC-OVARY-SYNDROME; REPRODUCTIVE ENDOCRINE DISORDERS; DIABETES-MELLITUS; PARTIAL SEIZURES; WEIGHT-GAIN; EPILEPSY; PREVALENCE; RISK; SCHIZOPHRENIA; ABNORMALITIES AB Background: Preliminary evidence suggests that valproate is associated with isolated features of polycystic ovarian syndrome (PCOS), while contradictory data support an association between epilepsy and PCOS. The development of PCOS features after initiation of valproate was therefore examined in women with bipolar disorder using a standardized definition of PCOS. Methods: Three hundred women 18 to 45 years old with bipolar disorder were evaluated for PCOS at 16 Systematic Treatment Enhancement for Bipolar Disorder sites. A comparison was made between the incidence of hyperandrogenism (hirsutism, acne, male-pattern alopecia, elevated androgens) with oligoamenorrhea that developed while taking valproate versus other anticonvulsants (lamotrigine, topiramate, gabapentin, carbamazepine, oxcarbazepine) and lithium. Medication and menstrual cycle histories were obtained, and hyperandrogenism was assessed. Results: Among 230 women who could be evaluated, oligoamenorrhea with hyperandrogenism developed in 9 (10.5%) of 86 women on valproate and in 2 (1.4%) of 144 women on a nonvalproate anticonvulsant or lithium (relative risk 7.5, 95% confidence interval [CI] 1.7-34.1, p = .002). Oligoamenorrhea always began within 12 months of valproate use. Conclusions. Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism. Monitoring for reproductive-endocrine abnormalities is important when starting and using valproate in reproductive-aged women. Prospective studies are needed to elucidate risk factors for development of PCOS on valproate. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Stanford Univ, Sch Med, Hlth Res & Policy Dept, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Reprod Endocrine Unit,Dept Med, Boston, MA 02115 USA. RP Joffe, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, 185 Cambridge St,Suite 2296, Boston, MA 02114 USA. EM hjoffe@partners.org FU NIMH NIH HHS [N01MH60006, N01MH60011, N01MH60013, N01MH60012, N01MH60014] NR 46 TC 62 Z9 63 U1 2 U2 3 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 JUN 1 PY 2006 VL 59 IS 11 BP 1078 EP 1086 DI 10.1016/j.biopsych.2005.10.017 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 054ZB UT WOS:000238416000014 PM 16448626 ER PT J AU Mapara, MY Leng, C Kim, YM Bronson, R Lokshin, A Luster, A Sykes, M AF Mapara, MY Leng, C Kim, YM Bronson, R Lokshin, A Luster, A Sykes, M TI Expression of chemokines in GVHD target organs is influenced by conditioning and genetic factors and amplified by GVHR SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE bone marrow transplantation; graft-versus-host disease; chemokine; CXCR3; knockout mouse ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE ALLOGRAFT-REJECTION; ANTIGEN-PRESENTING CELLS; T-LYMPHOCYTES; DIFFERENTIAL ROLES; HUMAN CYTOKINES; CC CHEMOKINES; TNF-ALPHA; GRAFT AB Graft-versus-host disease (GVHD) is the most significant clinical problem that arises after allogeneic hematopoietic cell transplantation. Because chemokines induced by proinflammatory conditioning treatment may promote T-cell migration into GVHD target tissues, we addressed the influence of conditioning on chemokine expression in GVHD target organs. Our results showed that (1) conditioning leads to rapid and transient chemokine upregulation in GVHD target tissues before the time of GVHD-associated T-cell infiltration; (2) conditioning intensity and mouse strain influence chemokine expression in GVHD target organs; and (3) compared with syngeneic bone marrow transplantation, allogeneic bone marrow transplantation led to marked amplification of chemokine expression in GVHD target organs after myeloablative conditioning. This is also reflected by chemokine protein expression that is measured in the serum and colon. Intestines showed the greatest sensitivity to conditioning intensity, and chemokines affecting T-helper type 1 cells (eg, interferon gamma-inducible protein 10 [CXCL10]) were most strongly expressed there after conditioning and during GVHD. However, severity of GVHD was not significantly different between recipients of CXCR3(+/+) or CXCR3(-/-) splenocytes, indicating that this chemokine pathway does not play a critical role. In summary, our data show that conditioning and recipient strain influence chemokine expression in GVHD target organs and that GVH alloreactivity markedly amplifies this expression, thus contributing to the inflammatory cascade associated with tissue GVHD. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect,Transplantat Biol R, Boston, MA USA. Univ Pittsburgh, Inst Canc, Div Hematol Oncol, Pittsburgh, PA USA. Humboldt Univ, Univ Med Ctr Charite, Dept Hematol Oncol & Tumor Immunol, Berlin, Germany. Univ Pittsburgh, Inst Canc, Luminex Facil, Pittsburgh, PA USA. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Bone Marrow Transplantat Sect,Transplantat Biol R, Bldg 149-5102, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu RI mapara, markus/A-2134-2013 FU NCI NIH HHS [R01CA79989] NR 41 TC 46 Z9 47 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2006 VL 12 IS 6 BP 623 EP 634 DI 10.1016/j.bbmt.2006.02.005 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 051SM UT WOS:000238181100004 PM 16737935 ER PT J AU Winston, DJ Biden, LR Gabriel, DA Emmanouilides, C Shaw, LM Lange, WR Ratanatharathorn, V AF Winston, DJ Biden, LR Gabriel, DA Emmanouilides, C Shaw, LM Lange, WR Ratanatharathorn, V TI Pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir in allogeneic stem cell transplant patients with graft-versus-host disease of the gastrointestinal tract SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE valganciclovir; pharmacokinetics; graft-versus-host disease ID BONE-MARROW-TRANSPLANTATION; CYTOMEGALOVIRUS DISEASE; PREEMPTIVE THERAPY; HUMAN PLASMA; HPLC METHOD; VIRAL LOAD; RECIPIENTS; PROPHYLAXIS; EFFICACY; PRODRUG AB The pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir were compared in allogencic stem cell transplant recipients with stable graft-versus-host disease of the gastrointestinal tract. Twenty-two evaluable adult patients were randomized to receive a single dose of open-label study drug (900 mg of oral valganciclovir or 5 mg/kg of intravenous ganciclovir). After a washout period of 2 to 7 days, patients were crossed over to receive the alternate study drug. Ganciclovir and valganciclovir concentrations in plasma were measured over 24 hours after dosing. Noninferiority of 900 mg of valganciclovir relative to intravenous ganciclovir was concluded if the lower limit of the 1-sided 95% confidence interval of the ratio of least-square means of the ganciclovir area under the curve (AUC) for the 2 study drugs was > 80%. Valganciclovir was found to be rapidly absorbed and converted into ganciclovir. The ganciclovir exposure after 900 mg of valganciclovir noninferior to that of intravenous ganciclovir (AUC(0-infinity), 52.1 and 53.8 mu g.h/mL, respectively; 95% confidence interval of the ratio of least square means of AUC(0-infinity) 82.48%-118.02%). Oral valganciclovir could be a useful alternative to intravenous ganciclovir in certain stable stem cell transplant patients who require prophylaxis or preemptive therapy for cytomegalovirus infection. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Univ Calif Los Angeles, Med Ctr, Dept Med, Los Angeles, CA 90095 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Roche Labs Inc, Med Affairs, Nutley, NJ USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. RP Winston, DJ (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Med, Room 42-121 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM dwinston@mednet.ucla.edu NR 21 TC 32 Z9 32 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2006 VL 12 IS 6 BP 635 EP 640 DI 10.1016/j.bbmt.2005.12.038 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 051SM UT WOS:000238181100005 PM 16737936 ER PT J AU Dinh, P Zhou, XH AF Dinh, P Zhou, XH TI Nonparametric statistical methods for cost-effectiveness analyses SO BIOMETRICS LA English DT Article DE confidence interval; cost-effectiveness analysis; Edgeworth expansion; incremental cost-effectiveness ratio; net health benefit; skewness ID CLINICAL-TRIAL DATA; CONFIDENCE-INTERVALS; EFFECTIVENESS RATIOS; RANDOMIZED-TRIAL; CARE; UNCERTAINTY; BENEFIT; SAMPLE AB Two measures often used in a cost-effectiveness analysis are the incremental cost-effectiveness ratio (ICER) and the net health benefit (NHB). Inferences on these two quantities are often hindered by highly skewed cost data. In this article, we derive the Edgeworth expansions for the studentized t-statistics for the two measures and show how they could be used to guide inferences. In particular, we use the expansions to study the theoretical performance of existing confidence intervals based on normal theory and to derive new confidence intervals for the ICER and the NHB. We conduct a simulation study to compare our new intervals with several existing methods. The methods evaluated include Taylor's interval, Fieller's interval, the bootstrap percentile interval, and the bootstrap bias-corrected acceleration interval. We found that our new intervals give good coverage accuracy and are narrower compared to the current recommended intervals. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence, Seattle, WA 98101 USA. RP Dinh, P (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM azhou@u.washington.edu FU AHRQ HHS [R01HS013105] NR 28 TC 17 Z9 17 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2006 VL 62 IS 2 BP 576 EP 588 DI 10.1111/j.1541-0420.2006.00509.x PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 054NP UT WOS:000238384500028 PM 16918923 ER PT J AU Betensky, RA Christian, CK Gustafson, ML Daley, J Zinner, MJ AF Betensky, RA Christian, CK Gustafson, ML Daley, J Zinner, MJ TI Hospital volume versus outcome: An unusual example of bivariate association SO BIOMETRICS LA English DT Article DE Kendall's tau; Pearson's correlation; Spearman's rho ID SURGICAL VOLUME; MORTALITY; SURGERY AB The Leapfrog Group, a consortium of more than 100 large employers, purchasing coalitions, and states that collectively provide health insurance to more than 33 million people, convened in 2000 with the goal of using market forces to improve the quality of healthcare. The resulting Leapfrog initiative suggested selective referral of complex procedures to high-volume hospitals and set volume thresholds for five procedures. This was based on the hypothesis that low-volume hospitals have higher mortality, which can be viewed in simplified statistical terms as the hypothesis that the binomial P is a decreasing function of n. The analysis of the correlation between hospitals' standardized mortality ratios (SMR, i.e., the ratio of observed to expected deaths) and hospitals' procedural volumes is revealing about the volume/mortality hypothesis. This presents an unusual pedagogic example in which the detection of correlation in the presence of nonlinear dependence is of primary interest, and thus the Pearson correlation is ideally suited. The frequently preferred nonparametric measures of bivariate association are inappropriate as they are unable to discriminate between correlation and dependence. C1 Harvard Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Betensky, RA (reprint author), Harvard Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02115 USA. EM betensky@hsph.harvard.edu FU NCI NIH HHS [CA75971] NR 8 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2006 VL 62 IS 2 BP 598 EP 604 DI 10.1111/j.1541-0420.2005.00449.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 054NP UT WOS:000238384500030 PM 16918925 ER PT J AU Priel, A Ramos, AJ Tuszynski, JA Cantiello, HF AF Priel, A Ramos, AJ Tuszynski, JA Cantiello, HF TI A biopolymer transistor: Electrical amplification by microtubules SO BIOPHYSICAL JOURNAL LA English DT Article ID ACTIN-FILAMENTS; CONTEXTUAL MEMORY; DENDRITES; NEURON; PROPAGATION; NEURITE; MODEL AB Microtubules (MTs) are important cytoskeletal structures engaged in a number of specific cellular activities, including vesicular traffic, cell cyto-architecture and motility, cell division, and information processing within neuronal processes. MTs have also been implicated in higher neuronal functions, including memory and the emergence of "consciousness''. How MTs handle and process electrical information, however, is heretofore unknown. Here we show new electrodynamic properties of MTs. Isolated, taxol-stabilized MTs behave as biomolecular transistors capable of amplifying electrical information. Electrical amplication by MTs can lead to the enhancement of dynamic information, and processivity in neurons can be conceptualized as an "ionic-based'' transistor, which may affect, among other known functions, neuronal computational capabilities. C1 Univ Alberta, Dept Phys, Edmonton, AB T6G 2J1, Canada. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Priel, A (reprint author), Univ Alberta, Dept Phys, Edmonton, AB T6G 2J1, Canada. EM apriel@phys.ualberta.ca; cantiello@helix.mgh.harvard.edu NR 29 TC 53 Z9 56 U1 1 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2006 VL 90 IS 12 BP 4639 EP 4643 DI 10.1529/biophysj.105.078915 PG 5 WC Biophysics SC Biophysics GA 048EX UT WOS:000237931500033 PM 16565058 ER PT J AU Perlman, CA Johnson, SL Mellman, TA AF Perlman, CA Johnson, SL Mellman, TA TI The prospective impact of sleep duration on depression and mania SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; depression; insomnia; mania; mood; sleep ID BIPOLAR DISORDER; SCALE; RELIABILITY; DEPRIVATION AB Objective: Many patients report sleeping less than 6 h per night during episodes of depression and mania. This type of sleep deficit may also be a risk factor for subsequent mood episodes; however, the long-term impact of sleep deficit remains unclear. The current study is among few longitudinal studies to assess the prospective effect of sleep deficit on depression and mania. Methods: A subsample of 54 individuals from a longitudinal study of bipolar I disorder was selected. Participants entered the study during a mood episode. Baseline symptom data were collected at month 4 to allow for recovery from the initial episode, sleep was assessed at month 6, and follow-up symptom data were obtained during months 7-12. Results: Sleep deficit predicted depressive symptoms across the 6-month follow-up but not mania. Conclusions: It is likely that the impact of sleep deficit on mania was probably missed because assessments covered a full month. Monitoring sleep duration may help predict depression in bipolar disorder and provide an opportunity for targeting intervention. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med & Dent, Boston, MA 02115 USA. Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. Howard Univ, Dept Psychiat, Mood & Anxiety Res Program, Washington, DC 20059 USA. RP Perlman, CA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 815,15 Parkman St, Boston, MA 02114 USA. EM cperlman@partners.org RI johnson, sheri/D-8712-2014 OI johnson, sheri/0000-0002-9945-4816 FU NIMH NIH HHS [R01 MH48171, R29 MH55950] NR 21 TC 55 Z9 56 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2006 VL 8 IS 3 BP 271 EP 274 DI 10.1111/j.1399-5618.2006.00330.x PG 4 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 042GM UT WOS:000237515900008 PM 16696829 ER PT J AU Owen, MH Coull, BA Holmes, LB AF Owen, Mary H. Coull, Brent A. Holmes, Lewis B. TI Asymmetry of skeletal effects of Dominant hemimelia SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Teratology-Society CY JUN 19-26, 2003 CL Philadelphia, PA SP Teratol Soc DE Dominant hemimelia; asymmetry; tibial hemimelia; asplenia; laterality defects ID RETINOIC ACID; LIMB DEFICIENCIES; SITUS-INVERSUS; MOUSE EMBRYO; NODAL FLOW; MALE-MICE; GENE; DH; SPLEEN; LETHALITY AB BACKGROUND: Dominant hemimelia (Dh) is a dominant mutation that arose spontaneously in mice; Dh animals exhibit reduced numbers of lumbar vertebrae and preaxial hindlimb defects. Absence of spleen occurs in both Dh/+ and Dh/Dh animals. This study was undertaken to characterize asymmetry of skeletal defects in the Dh mouse, specifically hindlimb asymmetries in association with axial defects. METHODS: A total of 29 Dh/+ and 100 +/+ fetuses (gestational day [GD] 18) were identified by phenotype and linked DNA and their skeletons were analyzed. RESULTS: The results revealed an asymmetry of hindlimb skeletal defects in Dh/+ animals. In +/+ fetuses, the left and right tibia were symmetrical with 99.0% of the animals possessing 6 lumbar vertebrae. However, Dh/+ fetuses showed asymmetry in length of left and right tibia and a reduction to 5 lumbar vertebrae in 86.2% of animals. There was a range from mild to severe asymmetry as evidenced by direct comparison of the length of the left to the right tibia of each animal. Tibial shortening was greater on the left than the right in 65.5% of Dh/+ fetuses; only 20.7% had symmetrical tibia. Oligodactyly, defined as absence of the first or second toe, was similarly more frequent on the left. CONCLUSIONS: Asymmetry is characteristic of many human limb malformations, although analysis of the molecular basis is difficult. Therefore, Dh/+ mice, which exhibit reduced numbers of lumbar vertebrae, asymmetric hindlimb defects, and complete absence of spleen, provide an important model for studying the relationship between axial patterning and asymmetric skeletal defects. C1 Simmons Coll, Dept Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Owen, MH (reprint author), Simmons Coll, Dept Biol, 300 Fenway, Boston, MA 02115 USA. EM mary.owen@simmons.edu NR 40 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUN PY 2006 VL 76 IS 6 BP 474 EP 482 DI 10.1002/bdra.20256 PG 9 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 080TM UT WOS:000240271300006 PM 16933211 ER PT J AU Winter, JN Weller, EA Horning, SJ Krajewska, M Variakojis, D Habermann, TM Fisher, RI Kurtin, PJ Macon, WR Chhanabhai, M Felgar, RE Hsi, ED Medeiros, LJ Weick, JK Reed, JC Gascoyne, RD AF Winter, JN Weller, EA Horning, SJ Krajewska, M Variakojis, D Habermann, TM Fisher, RI Kurtin, PJ Macon, WR Chhanabhai, M Felgar, RE Hsi, ED Medeiros, LJ Weick, JK Reed, JC Gascoyne, RD TI Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study SO BLOOD LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2003 CL SAN DIEGO, CA SP Amer Soc Hematol ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; 2-STAGE RANDOMIZATION DESIGNS; TREATMENT POLICIES; SIGNALING PATHWAY; ELDERLY-PATIENTS; CLINICAL-TRIALS; RITUXIMAB; SURVIVAL; GENE AB Bcl-6 protein expression, a marker of germinal center origin, has been associated with a favorable prognosis in diffuse large B-cell lymphoma (DLBCL). To determine the prognostic significance of this marker when rituximab (R) was added to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, we prospectively studied Bcl-6 protein expression by immunolhistochemical staining of 199 paraffin-embedded specimens from patients enrolled in the US Intergroup phase 3 trial comparing R-CHOP to CHOP with or without maintenance R. In Bcl-6(-) patients, failure-free survival (FFS) and overall survival (OS) were prolonged for those treated with R-CHOP alone compared to CHOP alone (2-year FFS 76% versus 9%, P < .001; 2-year OS 79% versus 17%, P < .001). In contrast, no differences in IFFS and OS were detected between treatment arms for Bcl-6(+) cases. In the multivariate analysis, treatment arm (CHOP versus R-CHOP) was the major determinant of both FFS (P < .001) and OS (P < .001) for the Bcl-6- subset, whereas the International Prognostic Index risk group was the only significant predictor of outcome among Bcl-6(+) cases. Bcl-2 protein expression was not predictive of outcome in either group. in this study, we observed a reduction in treatment failures and death with the addition of R to CHOP in Bcl-6(-) DLBCL cases only. Our finding that Bcl-6(+) cases did not benefit from the addition of R to CHOP requires independent confirmation. C1 Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Stanford, CA 94305 USA. Burnham Inst Med Res, La Jolla, CA USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ Rochester, James P Wilmot Canc Ctr, Med Ctr, Rochester, NY 14627 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Cleveland Clin, Cleveland, OH 44106 USA. MD Anderson Canc Ctr, Houston, TX USA. Hematol Oncol Associates Palm Beaches, Lake Worth, FL USA. RP Winter, JN (reprint author), Div Hematol Oncol, 676 N St Clair St,Ste 850, Chicago, IL 60611 USA. EM j-winter@northwestern.edu FU NCI NIH HHS [CA04949, CA17145, CA21115, CA32102, CA38926, CA92291, CA66636, CA23318, CA13650, CA11083] NR 40 TC 184 Z9 198 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2006 VL 107 IS 11 BP 4207 EP 4213 DI 10.1182/blood-2005-10-4222 PG 7 WC Hematology SC Hematology GA 047KD UT WOS:000237877300011 PM 16449523 ER PT J AU Taniguchi, T D'Andrea, AD AF Taniguchi, T D'Andrea, AD TI Molecular pathogenesis of Fanconi anemia: recent progress SO BLOOD LA English DT Review ID DNA-DAMAGE RESPONSE; DOUBLE-STRAND BREAKS; ACUTE MYELOID-LEUKEMIA; GROUP-A GENE; FANCD2 KNOCKOUT MICE; CROSS-LINK REPAIR; GROUP-C PROTEIN; HOMOLOGOUS RECOMBINATION; PANCREATIC-CANCER; OVARIAN-CANCER AB A rare genetic disease, Fanconi anemia (FA), now attracts broader attention from cancer biologists and basic researchers in the DNA repair and ubiquitin biology fields as well as from hematologists. FA is a chromosome instability syndrome characterized by childhood-onset aplastic anemia, cancer or leukemia susceptibility, and cellular hypersensitivity to DNA crosslinking agents. Identification of 11 genes for FA has led to progress in the molecular understanding of this disease. FA proteins, including a ubiquitin ligase (FANCL), a monoubiquitinated protein (FANCD2), a helicase (FANCJ/BACH1/BRIP1), and a breast/ovarian cancer susceptibility protein (FANCD1/BRCA2), appear to cooperate in a pathway leading to the recognition and repair of damaged DNA. Molecular interactions among FA proteins and responsible proteins for other chromosome instability syndromes (BLM, NBS1, MRE11, ATM, and ATR) have also been found. Furthermore, inactivation of FA genes has been observed in a wide variety of human cancers in the general population. These findings have broad implications for predicting the sensitivity and resistance of tumors to widely used anticancer DNA crosslinking agents (cisplatin, mitomycin C, and melphalan). Here, we summarize recent progress in the molecular biology of FA and discuss roles of the FA proteins in DNA repair and cancerbiology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu NR 149 TC 237 Z9 242 U1 3 U2 18 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 JUN 1 PY 2006 VL 107 IS 11 BP 4223 EP 4233 DI 10.1182/blood-2005-10-4240 PG 11 WC Hematology SC Hematology GA 047KD UT WOS:000237877300013 PM 16493006 ER PT J AU Wernig, G Mercher, T Okabe, R Levine, RL Lee, BH Gilliland, DG AF Wernig, G Mercher, T Okabe, R Levine, RL Lee, BH Gilliland, DG TI Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model SO BLOOD LA English DT Article ID CHRONIC MYELOPROLIFERATIVE DISORDERS; TYROSINE KINASE JAK2; MUTATION; HEMATOPOIESIS; CELL; ERYTHROPOIETIN; TRANSFORMATION; CHROMOSOME; LEUKEMIAS; CML AB An acquired somatic mutation, Jak2V617F, was recently discovered in most patients with polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), and essential thrombocythmia (ET). To investigate the role of this mutation in vivo, we transplanted bone marrow (BM) transduced with a retrovirus expressing either Jak2 wild-type (wt) or Jak2V617F into lethally irradiated syngeneic recipient mice. Expression of Jak2V617F, but not Jak2wt, resulted in clinicopathologic features that closely resembled PV in humans. These included striking elevation in hemoglobin level/hematocrit, leukocytosis, megakaryo-cyte hyperplasia, extramedullary hematopoiesis resulting in splenomegaly, and reticulin fibrosis in the bone marrow. Histopathologic and flow cytometric analyses showed an increase in maturing myeloid lineage progenitors, although megakaryocytes showed decreased polypioldization and staining for acetylcholinesterase. In vitro analysis of primary cells showed constitutive activation of Stat5 and cytokine-independent growth of erythroid colony-forming unit (CFU-E) and erythropoietin hypersensitivity, and Southern blot analysis for retroviral integration indicated that the disease was oligoclonal. Furthermore, we observed strain-specific differences in phenotype, with Balb/c mice demonstrating markedly elevated leukocyte counts, splenomegaly, and reticulin fibrosis compared with C57BI/6 mice. We conclude that Jak2V617F expression in bone marrow progenitors results in a PV-Iike syndrome with myelofibrosis and that there are strain-specific modifiers that may in part explain phenotypic pleiotropy of Jak2V617F-associated myeloproliferative disease in humans. C1 Harvard Univ, Sch Med, Div Hematol, Brigham & Womens Hosp,Dept Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Wernig, G (reprint author), Harvard Univ, Sch Med, Div Hematol, Brigham & Womens Hosp,Dept Med, 75 Francis St, Boston, MA 02215 USA. EM ggilliland@rics.bwh.harvard.edu RI Mercher, Thomas/J-2446-2014 OI Mercher, Thomas/0000-0003-1552-087X FU NCI NIH HHS [CA04002, CA66996]; NIDDK NIH HHS [DK50654] NR 25 TC 308 Z9 330 U1 0 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 JUN 1 PY 2006 VL 107 IS 11 BP 4274 EP 4281 DI 10.1182/blood-2005-12-4824 PG 8 WC Hematology SC Hematology GA 047KD UT WOS:000237877300020 PM 16478879 ER PT J AU Fujimi, S MacConmara, MP Maung, AA Zang, Y Mannick, JA Lederer, JA Lapchak, PH AF Fujimi, S MacConmara, MP Maung, AA Zang, Y Mannick, JA Lederer, JA Lapchak, PH TI Platelet depletion in mice increases mortality after thermal injury SO BLOOD LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; ACTIVATED PLATELETS; IMMUNE-RESPONSE; INDUCED IMMUNOSUPPRESSION; BLOOD-PLATELETS; BURNED PATIENTS; CD40 LIGAND; T-CELLS; EXPRESSION AB Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in innate and adaptive immunity. However, the role of platelets in the immune response to injury remains undefined. We tested the importance of platelets in the host response to serious injury in a newly developed platelet-deficient mouse model. Wild-type and platelet-depleted C57BL/6J mice underwent a 25% full-thickness total body surface area thermal or sham injury. Platelet-deficient mice showed survival of 51% at 48 hours after injury compared with 94% to 100% survival in experimental control mice (P <.001). Necropsy and histology ruled out hemorrhage and hypovolemia as causes of death. Percentages of peripheral blood monocytes (P <.01) and neutrophils (P <.05) were increased between 36 and 48 hours after thermal injury in platelet-deficient mice compared with control mice. Plasma levels of TNF alpha (P <.001), IL-6 (P <.001), and MCP-1 (P <.05) were also elevated by 24 hours whereas levels of TGF beta(1) were reduced between 24 and 36 hours following injury in platelet-depleted mice (P <.001) compared with control mice. Our findings demonstrate for the first time that platelets play a critical protective role during the host response to injury. Moreover, our findings suggest that platelets and, more importantly, platelet-derived TGFP(1) modulate the systemic inflammatory response occurring after injury. C1 Brigham & Womens Hosp, Dept Surg, Julian & Eunice Cohen Lab Surg Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Lapchak, PH (reprint author), Brigham & Womens Hosp, Dept Surg, Julian & Eunice Cohen Lab Surg Res, 75 Francis St, Boston, MA 02115 USA. EM plapchak@partners.org OI Lapchak, Peter/0000-0001-8597-088X FU NIGMS NIH HHS [GM05766406, GM062119-03] NR 55 TC 28 Z9 30 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2006 VL 107 IS 11 BP 4399 EP 4406 DI 10.1182/blood-2005-09-3776 PG 8 WC Hematology SC Hematology GA 047KD UT WOS:000237877300035 PM 16467203 ER PT J AU Loh, ML Goldwasser, MA Silverman, LB Poon, WM Vattikuti, S Cardoso, A Neuberg, DS Shannon, KM Sallan, SE Gilliland, DG AF Loh, ML Goldwasser, MA Silverman, LB Poon, WM Vattikuti, S Cardoso, A Neuberg, DS Shannon, KM Sallan, SE Gilliland, DG TI Prospective analysis of TEL/AML1-positive patients treated on Dana-Farber Cancer Institute consortium protocol 95-01 SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TEL-AML1 FUSION TRANSCRIPT; TEL/AML1 FUSION; GENE FUSION; PROGNOSTIC-SIGNIFICANCE; L-ASPARAGINASE; TEL GENE; CHILDHOOD; CHILDREN; RELAPSE AB In a retrospective analysis, we previously reported that children whose leukemia cells harbored the TEL/AML1 gene rearrangement have excellent outcomes. From 1996 to 2000, we conducted a prospective study to determine the incidence and outcomes of children with TEL/AML1-positive acute lymphoblastic leukemia (ALL). Children with newly diagnosed ALL were treated on DFCI ALL Consortium Protocol 95-01. Patients were risk stratified primarily by current National Cancer Institute (NCI)-Rome risk criteria. With a median follow-up of 5.2 years, the 5-year event-free survival for TEL/AML1-positive patients was 89% compared with 80% for TEL/AML1-negative B-precursor patients (P = .05). The 5-year overall survival rate was 97% among TEL/AML-positive patients compared with 89% among TEL/AML1-negative patients (P = .03). However, in a multivariable analysis, risk group (age and leukocyte count at diagnosis) and asparaginase treatment group, but not TEL/AML1 status, were found to be independent predictors of outcome. We conclude that TEL/AML1-positive patients have excellent outcomes, confirming our previous findings. However, factors such as age at diagnosis and presenting leukocyte count should be taken into consideration when treating this group of patients. C1 Univ Calif San Francisco, Ctr Comprehens Canc, Dept Pediat, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Acute Lymphoblast Leukemia Consortium, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Womens Hosp Med Ctr, Boston, MA USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Loh, ML (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, Dept Pediat, Room HSE-302,Box 0519, San Francisco, CA 94143 USA. EM lohm@peds.ucsf.edu FU NCI NIH HHS [P01 CA 68484, K23 CA80195] NR 32 TC 64 Z9 74 U1 0 U2 0 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 JUN 1 PY 2006 VL 107 IS 11 BP 4508 EP 4513 DI 10.1182/blood-2005-08-3451 PG 6 WC Hematology SC Hematology GA 047KD UT WOS:000237877300048 PM 16493009 ER PT J AU Harris, GJ Chabris, CF Clark, J Urban, T Aharon, I Steele, S McGrath, L Condouris, K Tager-Flusberg, H AF Harris, GJ Chabris, CF Clark, J Urban, T Aharon, I Steele, S McGrath, L Condouris, K Tager-Flusberg, H TI Brain activation during semantic processing in autism spectrum disorders via functional magnetic resonance imaging SO BRAIN AND COGNITION LA English DT Article DE autism; Asperger syndrome; autism spectrum disorders; functional magnetic resonance imaging; language; semantic processing ID INFERIOR PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; LANGUAGE-ASSOCIATION CORTEX; LONG-TERM-MEMORY; PARS TRIANGULARIS; ASPERGER-SYNDROME; CHILDHOOD AUTISM; PLANUM TEMPORALE; CORTICAL ANATOMY; EPISODIC MEMORY AB Language and communication deficits are core features of autism spectrum disorders (ASD), even in high-functioning adults with ASD. This study investigated brain activation patterns using functional magnetic resonance imaging in right-handed adult males with ASD and a control group, matched on age, handedness, and verbal IQ. Semantic processing in the controls produced robust activation in Broca's area (left inferior frontal gyrus) and in superior medial frontal gyrus and right cerebellum. The ASD group had substantially reduced Broca's activation, but increased left temporal (Wernicke's) activation. Furthermore, the ASD group showed diminished activation differences between concrete and abstract words, consistent with behavioral studies. The current study suggests Broca's area is a region of abnormal neurodevelopment in ASD, which may be linked with semantic and related language deficits frequently observed in ASD. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Harris, GJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM gjharris@partners.org RI Tager-Flusberg, Helen/D-5265-2009; OI McGrath, Lauren/0000-0001-6928-9656 FU NIDCD NIH HHS [P01/U19 DC 03610] NR 72 TC 110 Z9 115 U1 9 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD JUN PY 2006 VL 61 IS 1 BP 54 EP 68 DI 10.1016/j.bandc.2005.12.015 PG 15 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 054MZ UT WOS:000238382600006 PM 16473449 ER PT J AU Wang, ZGC Buraimoh, A Iglehart, JD Richardson, AL AF Wang, ZGC Buraimoh, A Iglehart, JD Richardson, AL TI Genome-wide analysis for loss of heterozygosity in primary and recurrent phyllodes tumor and fibroadenoma of breast using single nucleotide polymorphism arrays SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE fibroadenoma; loss of heterozygosity; phyllodes tumor; single nucleotide polymorphism array; stem or precursor cell ID CYSTOSARCOMA-PHYLLODES; HISTOLOGIC FEATURES; UTERINE LEIOMYOMAS; HYBRIDIZATION; EXPRESSION; ASSOCIATION; ABERRATIONS; CARCINOMAS; TP53; 1Q AB Phyllodes tumors of the breast are biphasic stromal and epithelial tumors histologically similar to benign fibroadenomas, but with a neoplastic stromal component. In contrast to fibroadenoma, phyllodes tumors can recur and be locally aggressive or be malignant. This study uses SNP array analysis to present a genome-wide map of loss of heterozygosity (LOH) in a cohort of phyllodes tumors and fibroadenomas. LOH is frequent and sometimes extensive in phyllodes tumors, but is rarely seen in fibroadenomas. There is heterogeneity between phyllodes tumors of different patients and no one LOH marker identifies a majority of these lesions. However, a subset of LOH loci occur in multiple cases of phyllodes tumors and are not found in fibroadenomas. Primary phyllodes tumors and paired recurrences from the same patient share common regions of LOH. In contrast, metachronous fibroadenomas from the same patient have different LOH patterns with no indication of a shared origin. Specific LOH loci may be associated with pathologic progression in recurrent phyllodes tumors. In a single case of phyllodes tumor containing a malignant epithelial component the malignant epithelium and stroma partially share an LOH genotype, suggesting a common precursor cell for the biphasic malignant components. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Richardson, AL (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM arichardson@partners.org FU NCI NIH HHS [NCI P50 CA89393-01] NR 27 TC 22 Z9 28 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2006 VL 97 IS 3 BP 301 EP 309 DI 10.1007/s10549-005-9124-5 PG 9 WC Oncology SC Oncology GA 056BX UT WOS:000238497100010 PM 16791486 ER PT J AU Johnson, PB Katz, LJ Rhee, DJ AF Johnson, PB Katz, LJ Rhee, DJ TI Selective laser trabeculoplasty: predictive value of early intraocular pressure measurements for success at 3 months SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; RANDOMIZED CLINICAL-TRIAL; TRABECULAR MESHWORK AB Aim: To determine the predictive value of the 2 week post-selective laser trabeculoplasty ( SLT) intraocular pressure ( IOP) by comparing it to the 4 week and 3 month values. Methods: A retrospective chart review of eyes that underwent SLT between 2001 and 2004 was performed. The primary outcome measure was IOP. Demographic and medical data were collected for correlational analysis. Results: 132 eyes of 95 patients were identified, none was excluded. Of the eyes that exhibited a decrease in IOP of > 1 mmHg at 2 weeks postoperatively, 99.24% continued to show a lowered IOP at the 4 week and 3 month visits. For these patients, the Pearson's r value between 2 weeks and 4 weeks was 0.708 ( p value = 0.01) while the r value between 2 weeks and 3 months was 0.513 ( p value = 0.01). Conclusions: The 2 week visit post-SLT predicted the 4 week and 3 month visits if the 2 week visit demonstrated a decrease in IOP. These findings suggest that those patients who had a decreased IOP at 2 weeks and are at their goal IOP may not need to be screened until 3 months postoperatively. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Wills Eye Hosp & Res Inst, William & Anna Goldberg Glaucoma Serv, Philadelphia, PA USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com NR 13 TC 26 Z9 28 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUN PY 2006 VL 90 IS 6 BP 741 EP 743 DI 10.1136/bjo.2205.086363 PG 3 WC Ophthalmology SC Ophthalmology GA 044DX UT WOS:000237653700023 PM 16464972 ER PT J AU Schoder, H Glass, EC Pecking, AP Harness, JK Wallace, AM Hirnle, P Alberini, JL Vilain, D Larson, SM Hoh, CK Vera, DR AF Schoder, Heiko Glass, Edwin C. Pecking, Alain P. Harness, Jay K. Wallace, Anne M. Hirnle, Peter Alberini, Jean L. Vilain, Didier Larson, Steven M. Hoh, Carl K. Vera, David R. TI Molecular targeting of the lymphovascular system for imaging and therapy SO CANCER AND METASTASIS REVIEWS LA English DT Article; Proceedings Paper CT 1st International Symposium on Cancer Metastasis and the Lymphovascular System CY APR 28-30, 2005 CL San Francisco, CA DE molecular targeting; PET; ultrasound; image fusion; endolymphatic therapy; sentinel lymph node mapping ID SENTINEL LYMPH-NODE; BREAST-CANCER PATIENTS; POSITRON-EMISSION-TOMOGRAPHY; GLUT-1 GLUCOSE-TRANSPORTER; BLEOMYCIN OIL SUSPENSION; FINE-NEEDLE-ASPIRATION; HEXOKINASE-II; AEROBIC GLYCOLYSIS; LYMPHOSCINTIGRAPHIC AGENTS; ENDOLYMPHATIC APPLICATION AB Progress toward targeting cancer cells is a multi-disciplinary endeavor. In addition to the surgical and oncology specialties, radiologists collaborate with mathematicians, computer scientists, and physicists, in a constant effort to incrementally improve upon the current imaging modalities. Recently, radiologists have formed collaborations with molecular biologists and chemists in order to develop molecular agents that target cancer cells via receptor-substrate or specific physiochemical interactions. In this review, we summarize selected efforts toward molecular targeting of the lymphovascular system. Standard imaging modalities, positron emission tomography, single photon emission tomography, and ultrasound, are reviewed as well as, the targeted introduction of substances for endolymphatic therapy. We also review the current status of sentinel lymph node mapping with radiocolloids and the application of molecular targeting for the development of a radiopharmaceutical specifically designed for sentinel lymph node mapping. C1 Moores Univ Calif San Diego Canc Ctr, La Jolla, CA 92093 USA. Mem Sloan Kettering Canc Ctr, Dept Radiol Nucl Med, New York, NY 10021 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Nucl Med, Los Angeles, CA 90073 USA. Ctr Rene Huguenin, Dept Nucl Med, F-92210 St Cloud, France. St Joseph Hosp, Comprehens Breast Ctr, Orange, CA 92868 USA. Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. RP Vera, DR (reprint author), Moores Univ Calif San Diego Canc Ctr, 3855 Hlth Sci Dr 0819, La Jolla, CA 92093 USA. EM dvera@ucsd.edu NR 111 TC 21 Z9 21 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 2006 VL 25 IS 2 BP 185 EP 201 DI 10.1007/s10555-006-8498-0 PG 17 WC Oncology SC Oncology GA 052YA UT WOS:000238268800003 PM 16770532 ER PT J AU Hoon, DSB Kitago, M Kim, J Mori, T Piris, A Szyfelbein, K Mihm, MC Nathanson, SD Padera, TP Chambers, AF Vantyghem, SA MacDonald, IC Shivers, SC Alsarraj, M Reintgen, DS Passlick, B Sienel, W Pantel, K AF Hoon, DSB Kitago, M Kim, J Mori, T Piris, A Szyfelbein, K Mihm, MC Nathanson, SD Padera, TP Chambers, AF Vantyghem, SA MacDonald, IC Shivers, SC Alsarraj, M Reintgen, DS Passlick, B Sienel, W Pantel, K TI Molecular mechanisms of metastasis SO CANCER AND METASTASIS REVIEWS LA English DT Article; Proceedings Paper CT 1st International Symposium on Cancer Metastasis and the Lymphovascular System CY APR 28-30, 2005 CL San Francisco, CA DE chemokines; intravital videoscopy; lymphatic vessels; lymph node; metastasis; oncogenes ID CELL LUNG-CANCER; LYMPH-NODE METASTASIS; INTERSTITIAL FLUID PRESSURE; POLYMERASE-CHAIN-REACTION; HUMAN-BREAST-CANCER; CUTANEOUS MALIGNANT-MELANOMA; ENDOTHELIAL GROWTH-FACTOR; DISSEMINATED TUMOR-CELLS; IN-VIVO VIDEOMICROSCOPY; EARLY-STAGE MELANOMA AB A major topic covered at the First International Symposium on Cancer Metastasis and the Lymphovascular System was the molecular mechanisms of metastasis. This has become of major interest in recent years as we have discovered new metastasis-related genes and gained understanding of the molecular events of lymphatic metastasis. The symposium covered new aspects and important questions related to the events of metastasis in both humans and animals. The basic and clinical related research covered in this topic represented many disciplines. The presentations showed novel findings and at the same time, raised many new unanswered questions, indicating the limited knowledge we still have regarding the molecular events of metastasis. The hope is that further unraveling of the direct and indirect molecular events of lymphatic metastasis will lead to new approaches in developing effective therapeutics. C1 John Wayne Canc Inst, Dept Mol Oncol, Santa Monica, CA 90404 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Josephine Ford Canc Ctr, Henry Ford Hlth Syst, Detroit, MI 48301 USA. Massachusetts Gen Hosp, EL Steele Labs Tumor Biol, Boston, MA 02114 USA. London Reg Canc Program, London, ON N6A 4L6, Canada. Univ Western Ontario, Dept Med Biophys, London, ON N6A 5C1, Canada. Lakeland Reg Canc Ctr, Lakeland, FL 33805 USA. Univ Freiburg, Dept Thorac Surg, D-79106 Freiburg, Germany. Univ Hamburg, Med Ctr, Inst Tumor Biol, D-20246 Hamburg, Germany. RP Hoon, DSB (reprint author), John Wayne Canc Inst, Dept Mol Oncol, Santa Monica, CA 90404 USA. EM hoon@jwci.org; mmihm@partners.org; dnathan1@hfhs.org; tpadera@steele.mgh.harvard.edu; ann.chambers@Lhsc.on.ca; svantygh@uwo.ca; imacd@uwo.ca; doug.reintgen@lrmc.com; wulf.sienel@uniklinik-freiburg.de; pantel@uke.uni-hamburg.de RI Shivers, Steve/E-6438-2013; Chambers, Ann/L-6285-2015; OI Shivers, Steve/0000-0001-9538-4016; Chambers, Ann/0000-0002-9509-5123; Hoon, Dave/0000-0003-1915-3683; Padera, Timothy/0000-0002-3453-9384 NR 175 TC 46 Z9 50 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 2006 VL 25 IS 2 BP 203 EP 220 DI 10.1007/s10555-006-8500-x PG 18 WC Oncology SC Oncology GA 052YA UT WOS:000238268800004 PM 16770533 ER PT J AU O'Riordan, DL Field, AE Geller, AC Brooks, DR Aweh, G Colditz, GA Frazier, AL AF O'Riordan, DL Field, AE Geller, AC Brooks, DR Aweh, G Colditz, GA Frazier, AL TI Frequent tanning bed use, weight concerns, and other health risk behaviors in adolescent females (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE adolescent females; tanning beds; health-risk behaviors; weight concerns and influences ID SUNSCREEN USE; FASHION MAGAZINES; PLANNED BEHAVIOR; SUN EXPOSURE; A-SUNBEDS; INDOOR; FACILITIES; TRENDS; WOMEN; ATTRACTIVENESS AB Objective To examine the association between tanning bed use and weight concerns, health risk behaviors, and peer influence. Methods The Growing Up Today Study (GUTS) is an ongoing prospective cohort study of adolescents established in 1996. In 1999, a total of 6,373 adolescent females ages 12-18 (offspring of participants in the Nurses Health Study 2) completed the survey. Results Almost nine percent (8.6%) of the adolescent girls had used a tanning bed 1-9 times and an additional 5.4% had used tanning beds at least 10 times in the past year (frequent users). Logistic regression models revealed that frequent tanning bed use was associated with being highly concerned about weight (OR = 1.5, 95%CI = 1.1, 2.0), frequently dieting to lose weight (OR = 1.5, 95%CI = 1.1, 2.0), using laxatives or vomiting to control weight (OR = 3.6; 95%CI = 2.2-5.8), having friends who placed a lot of importance on being thin (OR = 2.6; 95%CI = 1.3-5.1), smoking cigarettes (OR=1.7, 95%CI = 1.1, 2.6), binge drinking (OR = 2.1, 95%CI = 1.3, 3.1), using recreational drugs (OR = 3.0; 95%CI = 2.4, 3.8), and trying to look like females in the media (sometimes/pretty much: OR = 1.3, 95%CI = 1.0, 1.8). Conclusion Frequent tanning bed use among adolescent females is associated with a range of health risk behaviors. This effect may be mediated by peer influence and a desire to look like other females in the media. Multi-pronged approaches, particularly those that target attitudes of young females, are needed to combat increased use of tanning beds. C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Univ Hawaii, Canc Res Ctr Hawaii, Prevent & Control Program, Honolulu, HI 96813 USA. Harvard Univ, Sch Med, Dept Med, Div Adolescent Med, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Psychiat, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Geller, AC (reprint author), Boston Univ, Sch Med, Dept Dermatol, 720 Harrison Ave,DOB 801A, Boston, MA 02118 USA. EM ageller@bu.edu RI Colditz, Graham/A-3963-2009 OI Brooks, Daniel/0000-0001-6220-6889; Colditz, Graham/0000-0002-7307-0291 NR 49 TC 50 Z9 50 U1 1 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2006 VL 17 IS 5 BP 679 EP 686 DI 10.1007/s10552-005-0453-9 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 035DQ UT WOS:000236980800008 PM 16633915 ER PT J AU Fantin, VR St-Pierre, J Leder, P AF Fantin, VR St-Pierre, J Leder, P TI Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance SO CANCER CELL LA English DT Article ID LACTATE-DEHYDROGENASE-A; HUMAN-BREAST TISSUES; AEROBIC GLYCOLYSIS; GLUCOSE-6-PHOSPHATE DEHYDROGENASE; PROLIFERATING CELLS; EPITHELIAL-CELLS; PROTEIN CAUSES; METABOLISM; CANCER; GROWTH AB Alterations in cellular metabolism are among the most consistent hallmarks of cancer. Herein we have investigated the relationship between increased aerobic lactate production and mitochondrial physiology in tumor cells. To diminish the ability of malignant cells to metabolize pyruvate to lactate, lactate dehydrogenase A (LDH-A) levels were knocked down by means of LDH-A short hairpin RNAs. Reduction in LDH-A activity resulted in stimulation of mitochondrial respiration and decrease of mitochondrial membrane potential. It also compromised the ability of these tumor cells to proliferate under hypoxia. The tumorigenicity of the LDH-A-deficient cells was severely diminished, and this phenotype was reversed by complementation with the human ortholog LDH-A protein. These results demonstrate that LDH-A plays a key role in tumor maintenance. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Leder, P (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. EM leder@genetics.med.harvard.edu NR 44 TC 689 Z9 725 U1 16 U2 86 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2006 VL 9 IS 6 BP 425 EP 434 DI 10.1016/j.ccr.2006.04.023 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 056HZ UT WOS:000238514400004 PM 16766262 ER PT J AU Davis, IJ Kim, JJ Ozsolak, F Widlund, HR Rozenblatt-Rosen, O Granter, SR Du, JY Fletcher, JA Denny, CT Lessnick, SL Linehan, WM Kung, AL Fisher, DE AF Davis, IJ Kim, JJ Ozsolak, F Widlund, HR Rozenblatt-Rosen, O Granter, SR Du, JY Fletcher, JA Denny, CT Lessnick, SL Linehan, WM Kung, AL Fisher, DE TI Oncogenic MITF dysregulation in clear cell sarcoma: Defining the MiT family of human cancers SO CANCER CELL LA English DT Article ID MICROPHTHALMIA TRANSCRIPTION FACTOR; WAARDENBURG SYNDROME TYPE-2; SOFT PART SARCOMA; MALIGNANT-MELANOMA; GENE FUSION; TFE3 GENE; CHROMOSOME-TRANSLOCATION; EWS/ATF1 ONCOGENE; LINEAGE SURVIVAL; LEUCINE-ZIPPER AB Clear cell sarcoma (CCS) harbors a pathognomonic chromosomal translocation fusing the Ewing's sarcoma gene (EWS) to the CREB family transcription factor ATF1 and exhibits melanocytic features. We show that EWS-ATF1 occupies the MITF promoter, mimicking melanocyte-stimulating hormone (MSH) signaling to induce expression of MITF, the melanocytic master transcription factor and an amplified oncogene in melanoma. Knockdown/rescue studies revealed that MITF mediates the requirement of EWS-ATF1 for CCS survival in vitro and in vivo as well as for melanocytic differentiation. Moreover, MITF and TFE3 reciprocally rescue one another in lines derived from CCS or pediatric renal carcinoma. Seemingly unrelated tumors thus employ distinct strategies to oncogenically dysregulate the MiT family, collectively broadening the definition of MiT-associated human cancers. C1 Dana Farber Canc Inst, Melanoma Program Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Calif Los Angeles, Gwynne Hazen Cherry Mem Labs, Div Hematol Oncol, Dept Pediat, Los Angeles, CA 90095 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Melanoma Program Med Oncol, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [CA100400, CA102309, K08 CA100400] NR 79 TC 91 Z9 96 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2006 VL 9 IS 6 BP 473 EP 484 DI 10.1016/j.ccr.2006.04.021 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 056HZ UT WOS:000238514400008 PM 16766266 ER PT J AU Ji, HB Li, DN Chen, L Shimamura, T Kobayashi, S McNamara, K Mahmood, U Mitchell, A Sun, YP Al-Hashem, R Chirieac, LR Padera, R Bronson, RT Kim, W Janne, PA Shapiro, GI Tenen, D Johnson, BE Weissleder, R Sharpless, NE Wong, KK AF Ji, Hongbin Li, Danan Chen, Liang Shimamura, Takeshi Kobayashi, Susumu McNamara, Kate Mahmood, Umar Mitchell, Albert Sun, Yangping Al-Hashem, Ruclayyah Chirieac, Lucian R. Padera, Robert Bronson, Roderick T. Kim, William Janne, Pasi A. Shapiro, Geoffrey I. Tenen, Daniel Johnson, Bruce E. Weissleder, Ralph Sharpless, Norman E. Wong, Kwok-Kin TI The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies SO CANCER CELL LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE; GENE-MUTATIONS; GEFITINIB SENSITIVITY; ACQUIRED-RESISTANCE; CANCER; INHIBITORS; ADENOCARCINOMAS; ERLOTINIB; CETUXIMAB AB To understand the role of human epidermal growth factor receptor (hEGFR) kinase domain mutations in lung tumorigenesis and response to EGFR-targeted therapies, we generated bitransgenic mice with inducible expression in type II pneumocytes of two common hEGFR mutants seen in human lung cancer. Both bitransgenic lines developed lung adenocarcinoma after sustained hEGFR mutant expression, confirming their oncogenic potential. Maintenance of these lung tumors was dependent on continued expression of the EGFR mutants. Treatment with small molecule inhibitors (erlotinib or HKI-272) as well as prolonged treatment with a humanized anti-hEGFR antibody (cetuximab) led to dramatic tumor regression. These data suggest that persistent EGFR signaling is required for tumor maintenance in human lung adenocarcinomas expressing EGFR mutants. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Ludwig Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ N Carolina, Sch Med, Dept Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Genet, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM kwong1@partners.org RI Tang, Amy/L-3226-2016; OI Tang, Amy/0000-0002-5772-2878; wong, kwok kin/0000-0001-6323-235X; Tenen, Daniel/0000-0002-6423-3888 FU NCI NIH HHS [CA90679]; NIA NIH HHS [AG024379, AG2400401] NR 45 TC 268 Z9 275 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2006 VL 9 IS 6 BP 485 EP 495 DI 10.1016/j.ccr.2006.04.022 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 056HZ UT WOS:000238514400009 PM 16730237 ER PT J AU Wu, K Giovannucci, E Byrne, C Platz, EA Fuchs, C Willett, WC Sinha, R AF Wu, K Giovannucci, E Byrne, C Platz, EA Fuchs, C Willett, WC Sinha, R TI Meat mutagens and risk of distal colon adenoma in a cohort of US men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; HETEROCYCLIC AMINE CONTENT; COLORECTAL-CANCER RISK; VARYING DEGREES; CONSUMPTION; PRODUCTS; EXPOSURE; CARCINOGENS; REPRODUCIBILITY; VALIDITY AB Cooking meats at high temperatures and for long duration produces heterocyclic amines and other mutagens. These meat-derived mutagenic compounds have been hypothesized to increase risk of colorectal neoplasia, but prospective data are unavailable. We examined the association between intakes of the heterocyclic amines 2-amino-3,8-dimethylimidazo[4, 5,-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,4,8-trimethylimidazo [4,5,-f]quinoxaline (DiMeIQx), and meat-derived mutagenicity (MDM) and risk of distal colon adenoma using a cooking method questionnaire administered in 1996 in the Health Professionals Follow-up Study cohort. Between 1996 and 2002, 581 distal colon adenoma cases were identified. Higher intake of MDM was marginally associated with increased risk of distal adenoma [fourth versus lowest quintile: odds ratio (OR), 1.39; 95% confidence interval (95% CI), 1.05-1.84; highest versus lowest quintile: OR, 1.29; 95% CI, 0.97-1.72; P-trend = 0.08]. Adjusting for total red meat or processed meat intake did not explain those associations. Our data also suggested a positive association between higher MeIQx (highest versus lowest quintile: OR, 1.28; 95% CI, 0.95-1.71; P-trend = 0.22) and risk of adenoma, but this association was attenuated after adjusting for processed meat intake. DiMeIQx and PhIP did not seem to be associated with risk of adenoma. In conclusion, higher consumption of mutagens from meats cooked at higher temperature and longer duration may be associated with higher risk of distal colon adenoma independent of overall meat intake. Because mutagens other than heterocyclic amines also contribute to MDM, our results suggest that mutagens other than heterocyclic amines in cooked meats may also play a role in increasing the risk of distal adenoma. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Georgetown Univ, Lombardi Canc Ctr, Canc Genet & Epidemiol Program, Washington, DC USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Wu, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Bldg 2,665 Huntington Ave, Boston, MA 02115 USA. EM kana.wu@channing.harvard.edu RI Sinha, Rashmi/G-7446-2015; Byrne, Celia/K-2964-2015 OI Sinha, Rashmi/0000-0002-2466-7462; Byrne, Celia/0000-0001-8289-4252 FU NCI NIH HHS [CA 55075, CA95589] NR 33 TC 59 Z9 60 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2006 VL 15 IS 6 BP 1120 EP 1125 DI 10.1158/1055-9965.EPI-05-0782 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053IZ UT WOS:000238300100011 PM 16775169 ER PT J AU Kulke, MH Muzikansky, A Clark, J Enzinger, PC Fidias, P Kinsella, K Michelini, A Fuchs, CS AF Kulke, MH Muzikansky, A Clark, J Enzinger, PC Fidias, P Kinsella, K Michelini, A Fuchs, CS TI A phase II trial of vinorelbine in patients with advanced gastroesophageal adenocarcinoma SO CANCER INVESTIGATION LA English DT Article DE gastric cancer; esophageal cancer; vinorelbine ID METASTATIC GASTRIC-CANCER; ADVANCED BREAST-CANCER; FOLINIC ACID; FLUOROURACIL; CARCINOMA; OXALIPLATIN; ESOPHAGEAL; CISPLATIN AB Platinum-based combination chemotherapy regimens increasingly are accepted as a first-line treatment option for patients with advanced gastroesophageal adenocarcinoma. While active, such regimens also have been associated with toxicity. Vinorelbine is both well tolerated and active in patients with advanced breast, lung cancer, and squamous cell carcinoma of the esophagus, but has not previously been evaluated as a single agent in gastroesophageal adenocarcinoma. We, therefore, performed a Phase II study to assess the activity of vinorelbine in this disease. Twenty-nine patients with previously treated or untreated metastatic gastroesophageal adenocarcinoma were treated with weekly vinorelbine, administered at a dose of 25 mg/m2, and were followed for evidence of radiologic response, toxicity, and survival. Patients received a median of 8 weeks of therapy. While mild myelosuppression was common, only 17 percent of the treated patients developed Grade 3 or Grade 4 neutropenia. Other toxicities included Grade 1-2 constipation in 31 percent, and Grade 1-2 neuropathy in 13 percent of patients. The overall radiologic response rate was 7 percent, the median progression-free survival time was 1.9 months and the median overall survival time was 7.8 months. We conclude that vinorelbine has minimal toxicity but only minor antitumor activity in patients with advanced gastroesophageal adenocarcinoma. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu FU NCI NIH HHS [K23 CA 093401]; NHLBI NIH HHS [K30 HL04095] NR 15 TC 6 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PD JUN-JUL PY 2006 VL 24 IS 4 BP 346 EP 350 DI 10.1080/07357900600705268 PG 5 WC Oncology SC Oncology GA 054YM UT WOS:000238414500002 PM 16777685 ER PT J AU Riemenschneider, MJ Betensky, RA Pasedag, SM Louis, DN AF Riemenschneider, MJ Betensky, RA Pasedag, SM Louis, DN TI AKT activation in human glioblastomas enhances proliferation via TSC2 and S6 kinase signaling SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR COMPLEX; CELL-GROWTH; SERINE PHOSPHORYLATION; MAXIMAL ACTIVATION; MAMMALIAN TARGET; CANCER CELLS; MTOR; TOR; PATHWAY; RAPAMYCIN AB Aberrant AKT (protein kinase B) signaling is common in many cancers, including glioblastoma. Current models suggest that AKT acts directly, or indirectly via the TSC complex, to activate the mammalian target of rapamycin (mTOR) as the main downstream mediator of AKT signaling. mTOR activation results in subsequent activation of S6K and STAT3, as well as suppression (i.e., phosphorylation) of 4E-BP1, leading to cell cycle progression and inhibition of apoptosis. Most studies of this pathway have used in vitro systems or tumor lysate-based approaches. We aimed to delineate these pathways in a primarily in situ manner using immunohistochemistry in a panel of 29 glioblastomas, emphasizing the histologic distribution of molecular changes. Within individual tumors, increased expression levels of p-TSC2, p-mTOR, p-4E-BP1, p-S6K, p-S6, and p-STAT3 were found in regions defined by elevated AKT activation. However, only TSC2, S6K, and S6 activation levels correlated significantly with AKT activation and clustered together in multidimensional scaling analyses. Ki-67 proliferation indices were significantly elevated in p-AKT-overexpressing regions, whereas expression of the apoptosis marker cleaved caspase 3 was generally low and not significantly different between the regions. These findings provide the first in vivo evidence for a close correlation between AKT and TSC2 phosphorylation levels in glioblastoma. Moreover, they suggest that downstream p-AKT effects are primarily mediated by S6 kinase signaling, thus enhancing proliferation rather than inhibiting apoptosis. C1 Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Mol Pathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Dusseldorf, Dept Neuropathol, D-4000 Dusseldorf, Germany. RP Louis, DN (reprint author), Massachusetts Gen Hosp E, Mol Pathol Unit 1497151, 149 13th St, Charlestown, MA 02129 USA. EM dlouis@partners.org FU NCI NIH HHS [CA57683] NR 40 TC 81 Z9 83 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2006 VL 66 IS 11 BP 5618 EP 5623 DI 10.1158/0008-5472.CAN-06-0364 PG 6 WC Oncology SC Oncology GA 049GC UT WOS:000238003100015 PM 16740698 ER PT J AU Solban, N Selbo, PK Sinha, AK Chang, SK Hasan, T AF Solban, Nicolas Selbo, Pal K. Sinha, Alok K. Chang, Sung K. Hasan, Tayyaba TI Mechanistic investigation and implications of photodynamic therapy induction of vascular endothelial growth factor in prostate cancer SO CANCER RESEARCH LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1; FACTOR MESSENGER-RNA; IN-VIVO; HOST MICROENVIRONMENT; TUMOR OXYGENATION; PLASMA-MEMBRANE; FLUENCE RATE; FACTOR VEGF; FACTOR GENE; CELLS AB Photodynamic therapy (PDT) is now an approved therapeutic modality, and induction of vascular endothelial growth factor (VEGF) following sulicurative PDT is of concern as VEGF may provide a survival stimulus to tumors. The processes that limit the efficacy of PDT warrant investigation so that mechanism-based interventions may be developed. This study investigates VEGF increase following sulicurative PDT using the photosensitizer benzoporphyrin derivative (BPD) both in an in vitro and in an orthotopic model of prostate cancer using the human prostate cancer cell line LNCaP. The two sulicurative doses used, 0.25 and 0.5 J/cm(2), mimicked subcurative PDT and elicited a 1.6- and 2.1-fold increase, respectively, in secreted VEGF 24 hours following PDT. Intracellular VEGF protein measurement and VEGF mRNA showed a 1.4- and 1.6-fold increase only at 0.5 J/cm(2). In vivo sulicurative PDT showed an increase in VEGF by both immunohistochemistry and ELISA. In vitro analysis showed no activation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) or cyclooxygenase-2 (COX-2) following subcurative PDT; furthermore, small interfering RNA inhibition of HIF-1 alpha and COX-2 inhibitor treatment had no effect on PDT induction of VEGF. PDT in the presence of phosphatidylinositol 3-kinase/AKT inhibitor or mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase inhibitor still induced VEGF. However, subcurative PDT increased phosphorylated p38 and stress-activated protein kinase/c-Jun NH(2)-terminal kinase. The p38 MAPK inhibitor abolished PDT induction of VEGF. The results establish the importance of VEGF in sulicurative BPD-PDT of prostate cancer and suggest possible molecular pathways for its induction. These findings should provide the basis for the development of molecular-based interventions for enhancing PDT and merit further studies. C1 Harvard Univ, Wellman Ctr Photomed, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Norwegian Radium Hosp, Inst Canc Res, Dept Radiat Biol, Oslo, Norway. RP Hasan, T (reprint author), Harvard Univ, Wellman Ctr Photomed, Massachusetts Gen Hosp, Sch Med, 40 Blossom St, Boston, MA 02114 USA. EM thasan@partners.org FU NCI NIH HHS [P01 CA84203] NR 49 TC 53 Z9 60 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 JUN 1 PY 2006 VL 66 IS 11 BP 5633 EP 5640 DI 10.1158/0008-5472.CAN-06-0604 PG 8 WC Oncology SC Oncology GA 049GC UT WOS:000238003100017 PM 16740700 ER PT J AU Berger, R Lin, DI Nieto, M Sicinska, E Garraway, LA Adams, H Signoretti, S Hahn, WC Loda, M AF Berger, R Lin, DI Nieto, M Sicinska, E Garraway, LA Adams, H Signoretti, S Hahn, WC Loda, M TI Androgen-dependent regulation of Her-2/neu in prostate cancer cells SO CANCER RESEARCH LA English DT Article ID RECEPTOR; KINASE; GROWTH; DIFFERENTIATION; MODULATION; CARCINOMA; ONCOGENE; PATHWAY; BINDING; GENES AB The mechanisms underlying the progression of prostate cancer to a state of resistance to hormone ablation remain poorly understood. Here, we have investigated the relationship between androgen receptor (AR) and Her-2/neu in prostate cancer cells. Overexpression of Her-2/neu (c-ErbB2) activates the AR pathway and confers a survival and growth advantage to prostate cancer cells in an androgen-deficient milieu. In vitro, the absence of androgens or All blockade induced Her-2/neu protein expression and phosphorylation. In contrast, upon readministration of androgens, Her-2/neu mRNA, protein, and phosphorylation levels decreased linearly with increasing concentrations of dihydrotestosterone as LNCaP cells reentered the cell cycle. In vivo, induction of Her-2/neu by castration in orthotopically injected LNCaP cells resulted in a progressive increase in prostate-specific antigen secretion into the mouse serum, indicating that Her-2/neumediated, All-dependent transcription occurs following castration and results in tumor cell growth. Finally, selection of LNCaP cells stably transfected with short hairpin RNA specific for AIR resulted in Her-2/neu overexpression. Similarly, knockdown of Her-2/neu led to induction of AR. However, when Her-2/neu and AR were simultaneously targeted, we observed cell death, whereas surviving cells retained low level expression of Her-2/neu. Thus, induction and activation of Her-2/neu occurs in an androgen-depleted environment or as a result of AR inactivation, promoting ablation-resistant survival of prostate cancer cells. These data provide the biochemical rationale to target Her-2/neu in hormone-refractory prostate cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D1536,44 Binney St, Boston, MA 02115 USA. EM william_habn@dfci.harvard.edu; massimo_loda@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172, 5P50CA90381, P01 CA089021] NR 20 TC 53 Z9 55 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2006 VL 66 IS 11 BP 5723 EP 5728 DI 10.1158/0008-5472.CAN-05-3928 PG 6 WC Oncology SC Oncology GA 049GC UT WOS:000238003100027 PM 16740710 ER PT J AU Kaminski, R Zagozdzon, R Fu, Y Mroz, P Fu, W Seng, S Avraham, S Avraham, HK AF Kaminski, R Zagozdzon, R Fu, Y Mroz, P Fu, W Seng, S Avraham, S Avraham, HK TI Role of Src kinases in Neu-induced tumorigenesis: Challenging the paradigm using Csk homologous kinase transgenic mice SO CANCER RESEARCH LA English DT Article ID PP60C-SRC PROTEIN-KINASE; NONRECEPTOR TYROSINE KINASE; BREAST-CANCER CELLS; MAMMARY TUMORIGENESIS; METASTATIC-DISEASE; MOLECULAR-CLONING; EXPRESSION; FAMILY; PROTOONCOGENE; GENE AB Amplification of the HER-2/neu (ErbB2) gene is observed in similar to 30% of human breast cancers, correlating with a poor clinical prognosis. Src kinases are also involved in the etiology of breast cancer, and their activation was suggested to be necessary for Neu-induced oncogenesis. To address whether Src activity is essential for Neu-mediated tumorigenesis, we used a physiologic inhibitor of Src kinase activity, the Csk homologous kinase (CHK), expressed as a mammary tissue-specific transgene. Our data, using a physiologic inhibitor of Src activity (CHK), showed that blocking of Neu-induced Src activity without altering Src expression levels had no significant effects on Neu-mediated mammary tumorigenesis in vivo. This contradicts the current paradigm that activation of Src kinases is essential for Neu-induced oncogenesis. This study is the first to distinguish between the kinase-dependent and kinase-independent actions of Src and shows that its kinase-dependent properties are not requisite for Neu-induced tumorigenesis. C1 Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Lab Photomed,Dept Dermatol, Boston, MA USA. RP Avraham, HK (reprint author), Beth Israel Deaconess Med Ctr, Div Expt Med, 3rd Floor,HIM Bldg,4 Blackfan Circle, Boston, MA 02115 USA. EM havraham@bidmc.harvard.edu RI Zagozdzon, Radoslaw/K-2141-2012 FU NCI NIH HHS [CA 096805]; PHS HHS [K18 PAR-02-069] NR 36 TC 8 Z9 10 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2006 VL 66 IS 11 BP 5757 EP 5762 DI 10.1158/008-5472.CAN-05-3536 PG 6 WC Oncology SC Oncology GA 049GC UT WOS:000238003100031 PM 16740714 ER PT J AU Cilingiroglu, M Oh, JH Sugunan, B Kemp, NJ Kim, J Lee, S Zaatari, HN Escobedo, D Thomsen, S Milner, TE Feldman, MD AF Cilingiroglu, M Oh, JH Sugunan, B Kemp, NJ Kim, J Lee, S Zaatari, HN Escobedo, D Thomsen, S Milner, TE Feldman, MD TI Detection of vulnerable plaque in a murine model of atherosclerosis with optical coherence tomography SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article; Proceedings Paper CT SCAI Meeting 2005 CY MAY, 2005 CL FL SP SCAI, Gen Elect DE vulnerable plaque; ApoE mice; OCT ID E-KNOCKOUT MOUSE; APOLIPOPROTEIN-E; ISCHEMIC DEATH; MICE; LESIONS; HYPERCHOLESTEROLEMIA; MACROPHAGE; THROMBOSIS; ARTERIES; RUPTURE AB Objectives: The aim of this study was to evaluate the feasibility of optical coherence tomography (OCT) to identify the components of vulnerable plaques in a well-established murine model of human atherosclerosis. Background: Although the pathologic features that predict plaque rupture at autopsy are well known, the development of a technology to identify these high risk features in vivo is lacking. OCT uses reflected light to provide histology-like images of plaque with higher resolution than competing imaging modalities. Whether OCT can reliably identify the features of an atherosclerotic plaque that define it as vulnerable-thin fibrous cap, large lipid core, and high percent of lipid in the artery-requires further study. Methods: OCT images of the atherosclerotic innominate artery segments from the apolipoprotein E knockout (apoE(-/-)) mice were recorded and correlated with histology in both in vivo (n = 7) and well as in ex vivo experiments (n = 12). Results: Excellent correlation between the OCT and histology measurements for fibrous cap thickness, lipid core size, and percentage lipid content was found. The fibrous cap thicknesses examined span those of human fibrous caps known to rupture (<65 mu m). Regions of greatest light reflection in OCT images were observed when calcium hydroxy-apatite was scattered in lipid, less in fibrous tissue, and least in lipid. Conclusions: These findings suggest that OCT holds promise for the identification of features defining vulnerable plaque including fibrous cap thickness, lipid core size, and the percentage of lipid content. (C) 2006 Wiley-Liss., Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Res & Dev Serv, San Antonio, TX USA. RP Feldman, MD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM feldmanm@uthscsa.edu FU NHLBI NIH HHS [HL59472] NR 27 TC 47 Z9 49 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN PY 2006 VL 67 IS 6 BP 915 EP 923 DI 10.1002/ccd.20717 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 050JA UT WOS:000238082300014 PM 16602128 ER PT J AU Baumgartl, J Baudler, S Scherner, M Babaev, VR Makowski, L Suttles, J McDuffie, M Tobe, K Kadowaki, T Fazio, S Kahn, CR Hotamisligil, GS Krone, W Linton, MF Bruning, JC AF Baumgartl, J Baudler, S Scherner, M Babaev, VR Makowski, L Suttles, J McDuffie, M Tobe, K Kadowaki, T Fazio, S Kahn, CR Hotamisligil, GS Krone, W Linton, MF Bruning, JC TI Myeloid lineage cell-restricted insulin resistance lirotects apolipoproteinE-deficient mice against atherosclerosis (vol 3, pg 247, 2006) SO CELL METABOLISM LA English DT Correction C1 Univ Cologne, Inst Genet, D-50931 Cologne, Germany. Ctr Mol Med Cologne, D-50931 Cologne, Germany. Univ Cologne, Klin & Poliklin Innere Med 2, D-50931 Cologne, Germany. Ctr Mol Med Cologne, D-50931 Cologne, Germany. Vanderbilt Univ, Cardiovasc Med Div, Nashville, TN 37235 USA. Harvard Univ, Sch Publ Hlth, Div Biol Sci, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02215 USA. Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. Univ Tokyo, Grad Sch Med, Dept Metab Dis, Tokyo 1138655, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Bruning, JC (reprint author), Univ Cologne, Inst Genet, D-50931 Cologne, Germany. EM jens.bruening@uni-koeln.de NR 1 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JUN PY 2006 VL 3 IS 6 BP 469 EP 469 DI 10.1016/j.cmet.2006.05.008 PG 1 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 051ZG UT WOS:000238199600011 ER PT J AU Tocco, G Illigens, BMW Malfroy, B Benichou, G AF Tocco, Georges Illigens, Ben M. -W. Malfroy, Bernard Benichou, Gilles TI Prolongation of alloskin graft survival by catalytic scavengers of reactive oxygen species SO CELLULAR IMMUNOLOGY LA English DT Article DE allotransplantation; cytokines; reactive oxygen species; skin graft; T-cells ID SALEN-MANGANESE COMPLEXES; ALLOREACTIVE T-CELLS; SUPEROXIDE-DISMUTASE; ALLOGRAFT-REJECTION; IN-VIVO; INFECTIOUS TOLERANCE; IMMUNE DEVIATION; INDUCED DAMAGE; FREE-RADICALS; MICE AB We tested the effects of salen manganese (Salen-Mn) complexes, which are scavengers of reactive oxygen species exhibiting superoxide dismutase and catalase activities on the rejection of and alloresponse to fully allogeneic skin grafts in mice. We showed that pre-transplant treatment of C57B1/6 don Dr skin or of BALB/c recipients with Salen-Mn complexes significantly delayed allograft rejection. ELISPOT analysis of alloimmune response of treated mice revealed a significant reduction of the frequency of type 1 cytokine (proinflammatory) producing T-cells, while the number of activated T-cells producing type 2 cytokines was elevated. In addition, anti-oxidative treatment of graft recipients resulted in a profound inhibition of their donor-specific cytotoxic T-cell response. Our results indicate that salen manganese complexes mediate their effect on graft rejection both by reducing the susceptibility of graft tissue to ROS-mediated injury and by exerting an anti-inflammatory effect in recipients. (c) 2006 Published by Elsevier Inc. C1 Harvard Univ, Sch Med, Cellular & Mol Immunol Lab,Transplantat Unit, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02115 USA. Eukar Inc, Bedford, MA 01730 USA. RP Benichou, G (reprint author), Harvard Univ, Sch Med, Cellular & Mol Immunol Lab,Transplantat Unit, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02115 USA. EM gbenichou@partners.org FU NEI NIH HHS [R01-EY013310] NR 46 TC 7 Z9 7 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUN PY 2006 VL 241 IS 2 BP 59 EP 65 DI 10.1016/j.cellimm.2006.06.009 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 105BA UT WOS:000242003100001 PM 16970930 ER PT J AU Goldstein, JN Camargo, CA Pelletier, AJ Edlow, JA AF Goldstein, JN Camargo, CA Pelletier, AJ Edlow, JA TI Headache in United States Emergency Departments: demographics, work-up and frequency of pathological diagnoses SO CEPHALALGIA LA English DT Article DE headache; emergency department; diagnosis; etiology ID SUBARACHNOID HEMORRHAGE; PRIMARY-CARE; ADOLESCENTS; MANAGEMENT; ADULTS AB Headache is a common complaint in the emergency department (ED). In order to examine headache work-ups and diagnoses across the USA, we queried a representative sample of adult ED visits (the National Hospital Ambulatory Medical Care Survey) for the years 1992-2001. Headache accounted for 2.1 million ED visits per year (2.2% of visits). Of the 14% of patients who underwent neuroimaging, 5.5% received a pathological diagnosis. Of the 2% of patients who underwent lumbar puncture, 11% received a pathological diagnosis. On multivariable analysis, a decreased rate of imaging was noted for patients without private insurance [odds ratio (OR) 0.61, confidence interval (CI) 0.44, 0.86] and for those presenting off-hours (OR 0.55, CI 0.39, 0.77). Patients over 50 were more likely to receive a pathological diagnosis (OR 3.3, CI 1.2, 9.3). In conclusion, clinicians should ensure that appropriate work-ups are performed regardless of presentation time or insurance status, and be vigilant in the evaluation of older patients. C1 Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Edlow, JA (reprint author), Beth Israel Deaconess Med Ctr, Dept Emergency Med, 1 Deaconess Rd, Boston, MA 02215 USA. EM jedlow@bidmc.harvard.edu RI Goldstein, Joshua/H-8953-2016 NR 40 TC 85 Z9 85 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD JUN PY 2006 VL 26 IS 6 BP 684 EP 690 DI 10.1111/j.1468-2982.2006.01093.x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 040YZ UT WOS:000237420900006 PM 16686907 ER PT J AU Burstein, HJ Mayer, E Partridge, AH O'Kane, H Litsas, G Come, SE Hudis, CA Goldstein, DF Muss, HB Winer, EP Garber, JE AF Burstein, Harold J. Mayer, Erica Partridge, Ann H. O'Kane, Holly Litsas, Georgia Come, Steven E. Hudis, Clifford A. Goldstein, Donald F. Muss, Hyman B. Winer, Eric P. Garber, Judy E. TI Inadvertent use of aromatase inhibitors in patients with breast cancer with residual ovarian function: Cases and lessons SO CLINICAL BREAST CANCER LA English DT Article DE estrogen; menopausal status; tamoxifen ID PREMENOPAUSAL WOMEN; THERAPY AB Aromatase inhibitors (Als) are important adjunctive therapy for postmenopausal women with hormone receptor-positive, early-stage breast cancer. At the present time, Als have no role for the management of breast cancer in premenopausal women. We report on several cases of the inadvertent use of Al therapy among women with residual ovarian function. A common experience in these cases was the onset of chernotherapy-related amenorrhea before initiation of A[ therapy, which confounded assessment of true menopausal status. We believe clinicians should be aware of the potential ovarian reserve among women with treatment-related amenorrhea so as to avoid use of Al therapy in patients in whom there is uncertainty about menopausal status. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Med Ctr, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Vermont, Burlington, VT 05405 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org FU NCI NIH HHS [T32 CA009172] NR 11 TC 17 Z9 17 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD JUN PY 2006 VL 7 IS 2 BP 158 EP 161 DI 10.3816/CBC.2006.n.026 PG 4 WC Oncology SC Oncology GA 112MP UT WOS:000242530400007 PM 16800976 ER PT J AU Takahashi, H Feuerhake, F Kutok, JL Monti, S Dal Cin, P Neuberg, D Aster, JC Shipp, MA AF Takahashi, H Feuerhake, F Kutok, JL Monti, S Dal Cin, P Neuberg, D Aster, JC Shipp, MA TI FAS death domain deletions and cellular FADD-like interleukin 1 beta converting enzyme inhibitory protein (long) overexpression: Alternative mechanisms for deregulating the extrinsic apoptotic pathway in diffuse large B-cell lymphoma subtypes SO CLINICAL CANCER RESEARCH LA English DT Article ID GERMINAL-CENTER REACTION; C-FLIP; HODGKINS-LYMPHOMA; MUTATIONS; EXPRESSION; GENE; ORIGIN AB Purpose: Large B-cell lymphomas (LBCL) arise from normal antigen-exposed B cells at germinal center (GC) or post-GC stages of differentiation. Negative selection of normal low-affinity or self-reactive GC B-cells depends on CD95 (FAS)-mediated apoptosis. FAS mutations that result in deletion of the cytoplasmic death domain destabilize the trimeric receptor and inhibit FAS-mediated apoptosis. This apoptotic pathway is also inhibited when the nuclear factor kappa B (NF kappa B) target, cellular FADD-like interleukin 1 beta converting enzyme inhibitory protein (cFLIP), interacts with the death-inducing signaling complex, assembled around the FAS death domain. Herein, we ask whether FAS death domain mutations and NF kappa B-mediated overexpression of cFLIP represent alternative mechanisms for deregulating the extrinsic apoptotic pathway in LBCL subtypes defined by gene expression profiling [oxidative phosphorylation, B-cell receptor/proliferation, and host response diffuse LBCLs and primary mediastinal LBCLs]. Experimental Design: The FAS receptor was sequenced, FAS death domain mutations identified, and cFLIP expression assessed in a series of primary LBCLs with gene expression profiling defined subtype designations and additional genetic analyses [t(14;18) and t(3;v)]. Results: FAS death domain deletions were significantly more common in oxidative phosphorylation tumors, which also have more frequent t(14;18), implicating structural abnormalities of either the extrinsic or intrinsic pathway in this diffuse LBCL subtype. In marked contrast, host response tumors, which have up-regulation of multiple NF kappa B target genes and increased NF kappa B activity, express significantly higher levels of cFLIP(long). Conclusions: These data suggest that the gene expression profiling-defined LBCL subtypes have different mechanisms for deregulating FAS-mediated cell death and, more generally, that these tumor groups differ with respect to their underlying genetic abnormalities. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Broad Inst, Cambridge, MA USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu OI Monti, Stefano/0000-0002-9376-0660 NR 24 TC 23 Z9 26 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 BP 3265 EP 3271 DI 10.1158/1078-0432.CCR-06-0076 PN 1 PG 7 WC Oncology SC Oncology GA 051OG UT WOS:000238169800007 PM 16740746 ER PT J AU Cook, RJ Coleman, R Brown, J Lipton, A Major, P Hei, YJ Saad, F Smith, MR AF Cook, RJ Coleman, R Brown, J Lipton, A Major, P Hei, YJ Saad, F Smith, MR TI Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ZOLEDRONIC ACID; RESORPTION; TURNOVER AB Purpose: To evaluate the relative prognostic value for specific markers of osteoblast and osteoclast activity while controlling for previously reported prognostic variables among men with hormone-refractory metastatic prostate cancer. Experimental Design: The 643 subjects in this report were participants in multicenter randomized controlled trial of zoledronic acid in men with metastatic prostate cancer. All subjects had bone metastases and disease progression despite medical or surgical castration. Relationships between baseline covariates and overall survival were examined by Cox proportional hazard model. Serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide were assessed as representative specific markers of osteoblast and osteoclast activity, respectively. Other covariates in the model were age, log prostate-specific antigen, hemoglobin, lactate dehydrogenase, albumin, analgesic use, and Eastern Cooperative Oncology Group performance status. Results: Serum BAP was significantly correlated with urinary N-telopeptide (correlation coefficient = 0.674; 95% confidence interval, 0.628-0.715; P < 0.0001). In univariate analyses, higher levels of serum BAP and urinary N-telopeptide levels were significantly associated with shorter overall survival. After controlling for the other variables, including N-telopeptide, in multivariate models, higher serum BAP levels were consistently associated with shorter survival. In contrast, urinary N-telopeptide levels were not significantly associated with survival in multivariate analyses. Variables retained in the reduced multivariate model were age, log prostate - specific antigen, hemoglobin, lactate dehydrogenase, analgesic use, and BAR Conclusions: Serum BAP significantly correlates with urinary N-telopeptide in men with androgen-independent prostate cancer and bone metastases. In multivariate models, higher levels of serum BAP but not urinary N-telopeptide are associated with shorter overall survival. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada. Weston Pk Hosp, Acad Unit Clin Oncol, Sheffield, S Yorkshire, England. Milton S Hershey Med Ctr, Hershey, PA USA. Hamilton Reg Canc Ctr, Hamilton, ON L8V 1C3, Canada. McMaster Univ, Dept Med, Hamilton, ON, Canada. Novartis Pharmaceut Corp, E Hanover, NJ USA. Univ Montreal, Ctr Hosp, Hop Notre Dame, Montreal, PQ, Canada. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu NR 11 TC 92 Z9 94 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 BP 3361 EP 3367 DI 10.1158/1078-0432.CCR-06-0269 PN 1 PG 7 WC Oncology SC Oncology GA 051OG UT WOS:000238169800019 PM 16740758 ER PT J AU Reckamp, KL Krysan, K Morrow, JD Milne, GL Newman, RA Tucker, C Elashoff, RM Dubinett, SM Figlin, RA AF Reckamp, KL Krysan, K Morrow, JD Milne, GL Newman, RA Tucker, C Elashoff, RM Dubinett, SM Figlin, RA TI A phase I trial to determine the optimal biological dose of celecoxib when combined with erlotinib in advanced non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; MAJOR URINARY METABOLITE; TYROSINE KINASE; CYCLOOXYGENASE-2 INHIBITOR; PROSTAGLANDIN E-2; EGF RECEPTOR; GEFITINIB; MUTATIONS; THERAPY; CHEMOPREVENTION AB Purpose: Overexpression of cyclooxygenase-2 (COX-2) activates extracellular signal-regulated kinase/mitogen-activated protein kinase signaling in an epidermal growth factor receptor (EGFR) tyrosine kinase inhibition (TKI) - resistant manner. Because preclinical data indicated that tumor COX-2 expression caused resistance to EGFR TKI, a phase I trial to establish the optimal biological dose (OBD), defined as the maximal decrease in urinary prostaglandin E-M (PGE-M), and toxicity profile of the combination of celecoxib and erlotinib in advanced non - small cell lung cancer was done. Experimental Design: Twenty-two subjects with stage IIIB and/or IV non - small cell lung cancer received increasing doses of celecoxib from 200 to 800 mg twice daily (bid) and a fixed dose of erlotinib. Primary end points included evaluation of toxicity and determination of the OBD of celecoxib when combined with erlotinib. Secondary end points investigate exploratory biological markers and clinical response. Results: Twenty-two subjects were enrolled, and 21 were evaluable for the determination of the OBD, toxicity, and response. Rash and skin-related effects were the most commonly reported toxicities and occurred in 86%. There were no dose-limiting toxicities and no cardiovascular toxicities related to study treatment. All subjects were evaluated on intent to treat. Seven patients showed partial responses (33%), and five patients developed stable disease (24%). Responses were seen in patients both with and without EGFR-activating mutations. A significant decline in urinary PGE-M was shown after 8 weeks of treatment, with an OBD of celecoxib of 600 mg bid. Conclusions: This study defines the OBD of celecoxib when combined with a fixed dose of EGFR TKI. These results show objective responses with an acceptable toxicity profile. Future trials using COX-2 inhibition strategies should use the OBD of celecoxib at 600 mg bid. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. Univ Texas, MD Anderson Canc Ctr, Pharmaceut Dev Ctr, Houston, TX 77030 USA. OSI Pharmaceut Inc, Boulder, CO USA. RP Reckamp, KL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, 10945 LeConte Ave,Suite 2333, Los Angeles, CA 90095 USA. EM kreckamp@mednet.ucla.edu RI Milne, Ginger/D-7648-2014; OI Milne, Ginger/0000-0003-3890-151X; Reckamp, Karen/0000-0002-9213-0325 FU NCI NIH HHS [CA77839, P50CA90388]; NIDDK NIH HHS [DK48831]; NIEHS NIH HHS [ES13125]; NIGMS NIH HHS [GM15431] NR 42 TC 71 Z9 80 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 BP 3381 EP 3388 DI 10.1158/1078-0432.CCR-06-0112 PN 1 PG 8 WC Oncology SC Oncology GA 051OG UT WOS:000238169800022 PM 16740761 ER PT J AU Zheng, X Chang, RL Cui, XX Avila, GE Hebbar, V Garzotto, M Shih, WCJ Lin, Y Lu, SE Rabson, AB Kong, ANT Conney, AH AF Zheng, X Chang, RL Cui, XX Avila, GE Hebbar, V Garzotto, M Shih, WCJ Lin, Y Lu, SE Rabson, AB Kong, ANT Conney, AH TI Effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice SO CLINICAL CANCER RESEARCH LA English DT Article ID KINASE-C-DELTA; ESTER-INDUCED APOPTOSIS; TRANS-RETINOIC ACID; N-TERMINAL KINASE; PHASE-II TRIAL; PROTEIN-KINASE; PHORBOL ESTER; ESTRAMUSTINE PHOSPHATE; CERAMIDE SYNTHASE; GENE-EXPRESSION AB Purpose: To investigate the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with paclitaxel (Taxol) on prostate cancer cells cultured in vitro or grown as tumors in immunodeficient mice. Experimental Design: Human prostate cancer LNCaP cells in culture were treated with TPA alone or in combination with paclitaxel. NCr immunodeficient mice with well-established LNCaP tumors received i.p. injections with vehicle or with TPA, paclitaxel, or TPA in combination with paclitaxel. The animals either received daily treatment for 5 consecutive days followed by a 2-day intermission, which was repeated for a total of 28 days (experiment 1), or continuous daily treatment for 28 days (experiment 2). Results: Treatment of LNCaP cells with a combination of TPA and paclitaxel synergistically inhibited the growth and induced apoptosis in cultured LNCaP cells, and this treatment also induced a marked increase in phosphorylated c-Jun-NH2-kinase (JNK). In animal experiments, tumor growth occurred in all mice treated with vehicle. When treated with TPA alone, the percentage of animals with some tumor regression was 33% in experiment 1 and 100% in experiment 2. Treatment of animals with paclitaxel alone caused some tumor regression in 17% and 57% of the animals in experiments 1 and 2, respectively. All animals treated with TPA + paclitaxel in both experiments had some tumor regression. Conclusions: TPA and paclitaxel in combination had a stronger inhibitory effect on the growth of LNCaP cells in culture or as xenograft tumors in immunodeficient mice than either agent alone. Clinical trials with TPA alone or in combination with paclitaxel in patients with prostate cancer may be warranted. C1 Rutgers State Univ, Ernest Mario Sch Pharm, Susan Lehman Cullman Lab Canc Res, Dept Biol Chem, Piscataway, NJ 08854 USA. Rutgers State Univ, Ernest Mario Sch Pharm, Susan Lehman Cullman Lab Canc Res, Dept Pharmaceut, Piscataway, NJ USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Oregon Hlth & Sci Univ, Dept Surg, Portland, OR USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Med & Dent New Jersey, Sch Publ Hlth, Div Biometr, Newark, NJ 07103 USA. Canc Inst New Jersey, New Brunswick, NJ USA. RP Conney, AH (reprint author), Rutgers State Univ, Ernest Mario Sch Pharm, Susan Lehman Cullman Lab Canc Res, Dept Biol Chem, 164 Frelinghuysen Rd, Piscataway, NJ 08854 USA. EM aconney@rci.rutgers.edu FU NCI NIH HHS [CA 092268] NR 35 TC 19 Z9 19 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 BP 3444 EP 3451 DI 10.1158/1078-0432.CCR-05-2823 PN 1 PG 8 WC Oncology SC Oncology GA 051OG UT WOS:000238169800030 PM 16740769 ER PT J AU Schilsky, RL McIntyre, OR Holland, JF Frei, E AF Schilsky, RL McIntyre, OR Holland, JF Frei, E TI A concise history of the cancer and Leukemia Group B SO CLINICAL CANCER RESEARCH LA English DT Article AB A formal National Cancer Institute Clinical Trials Cooperative Group Program was conceived in 1955 when Dr. Sidney Farber, Mary-Lasker, and others approached Congress with a proposal to increase support for studies of chemotherapy of cancer. In response, Congress awarded US $5 million to the National Cancer Institute to establish the Chemotherapy National, Service Center. The founders of the Cancer and Leukemia Group B, James Holland and Emil (Tom) Frei, III, envisioned that successful chemotherapy for leukemia and other hematologic malignancies could be expeditiously realized through carefully designed clinical trials executed uniformly as a cooperative effort among several institutions. In 1956, the group was designated the Acute Leukemia Group B by the Chemotherapy National, Service Center Clinical, Studies, Panel, and Frei was elected chairman. In the ensuing 50 years, the Cancer and Leukemia Group B has expanded to national and even international membership, and its research programs have expanded to include all of the common adult solid tumors and hematologic malignancies in a multidisciplinary effort to improve the outcomes for patients with cancer and to better understand the biology of malignant disease. C1 Cent Off Chairman, Canc & Leukemia Grp B, Chicago, IL 60606 USA. Univ Chicago, Chicago, IL 60637 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Mt Sinai Hosp Med Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schilsky, RL (reprint author), Cent Off Chairman, Canc & Leukemia Grp B, 230 W Monroe St,Suite 2050, Chicago, IL 60606 USA. EM rs27@uchicago.edu NR 1 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 SU S BP 3553S EP 3555S DI 10.1158/1078-0432.CCR-06-9000 PN 2 PG 3 WC Oncology SC Oncology GA 052IR UT WOS:000238227900001 PM 16740784 ER PT J AU Larson, RA Stone, RM Mayer, RJ Schiffer, CA AF Larson, RA Stone, RM Mayer, RJ Schiffer, CA TI Fifty years of clinical research by the Leukemia Committee of the Cancer and Leukemia Group B SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; RESISTANCE MODULATOR PSC-833; ACUTE PROMYELOCYTIC LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; RANDOMIZED CONTROLLED-TRIAL; HIGH-DOSE CYTARABINE; TRANS-RETINOIC ACID; UNTREATED PATIENTS AB Progress in the care of patients with leukemia has been one of the great success stories in the field of oncology, and clinical research in leukemia has been the "flagship" of the Cancer and Leukemia Group B since the inception of this organization. Lessons learned from the founders emphasis on childhood and adult leukemia have been extended broadly over the past 50 years to virtually all types of malignant diseases, and the Leukemia, Committee has continued to provide leadership and key contributions. The Leukemia Committee is focused on the individualization of treatment based on distinctive biological and clinical characteristics with the aim of increasing efficacy and decreasing nonspecific toxicity. Our clinical trials in leukemia and myeloma have shifted from primarily empirically derived comparisons of different chemotherapeutic regimens to testing novel concepts such as the role of dose intensity, inhibition of specific mechanisms of drug resistance, the use of hematopoietic growth factors and monoclonal antibodies, and the utility of targeted agents. The Cancer and Leukemia Group B was the pioneer among the cooperative groups in the creation of centralized tissue repositories and the incorporation of correlative laboratory studies as an integral feature of clinical trials, a practice now termed "translational research. "Considerable effort: has focused on the identification of important pretreatment characteristics, such as morphologic features, immunophenotype, chromosomal abnormalities, and molecular defects which are significantly associated with outcome in multivariable analyses and which enhance our understanding for the complex biology of these diseases. C1 Univ Chicago, Hematol Oncol Sect, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Ctr Canc Res, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. RP Larson, RA (reprint author), Univ Chicago, Hematol Oncol Sect, Dept Med, MC-2115,5841 S Maryland Ave, Chicago, IL 60637 USA. EM rlarson@medicine.bsd.uchicago.edu OI Larson, Richard/0000-0001-9168-3203 NR 30 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 SU S BP 3556S EP 3563S DI 10.1158/1078-0432.CCR-06-9001 PN 2 PG 8 WC Oncology SC Oncology GA 052IR UT WOS:000238227900002 PM 16740785 ER PT J AU Cheson, BD Canellos, GP AF Cheson, BD Canellos, GP TI The Cancer and Leukemia Group B Lymphoma Committee SO CLINICAL CANCER RESEARCH LA English DT Article ID ADVANCED HODGKINS-DISEASE; LARGE-CELL LYMPHOMA; PROTEASOME INHIBITOR BORTEZOMIB; ANTI-CD30 MONOCLONAL-ANTIBODY; TERM-FOLLOW-UP; COMBINATION CHEMOTHERAPY; PHASE-II; INTERGROUP TRIAL; MOPP/ABV HYBRID; EFFICACY AB The malignant lymphomas include at least 30 entities that are distinct with respect to histology immunology, genetics clinical features and outcome following therapy. The clinical behavior of these diseases ranges from indolent but generally incurable to aggressive and frequently fatal yet potentially curable with appropriate chemotherapy or chemotherapy-antibody regimens. Over the past 50 years, the Cancer and Leukemia Group B (CALGB). Lymphoma Committee has conducted a series of clinical trials that have contributed to an improvement in outcome for patients with a number of the more common lymphoma subtypes. C1 Georgetown Univ Hosp, Div Hematol Oncol, Washington, DC 20007 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cheson, BD (reprint author), Georgetown Univ Hosp, Div Hematol Oncol, 3800 Reservoir Rd, Washington, DC 20007 USA. EM bdc4@georgetown.edu NR 39 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 SU S BP 3572S EP 3575S DI 10.1158/1078-0432.CCR-06-9003 PN 2 PG 4 WC Oncology SC Oncology GA 052IR UT WOS:000238227900004 PM 16740787 ER PT J AU Hudis, CA Winer, EP AF Hudis, CA Winer, EP TI Cancer and Leukemia Group B Breast Committee: Decades of progress and plans for the future SO CLINICAL CANCER RESEARCH LA English DT Article ID SURGICAL ADJUVANT BREAST; HIGH-DOSE CHEMOTHERAPY; STAGE-II; CYCLOPHOSPHAMIDE; CARCINOMA; FLUOROURACIL; BEVACIZUMAB; REGIMEN; TRIAL; WOMEN AB The Breast Committee of the Cancer and Leukemia Group B was formed in 1969 under the direction of James Holland. Initial studies examined combination chemotherapy for advanced disease. Although the committee has continued to conduct studies in patients with advanced disease, adjuvant therapy has been an even more important focus for the past 30 years. Over the past 20 years, studies have focussed on optimization of chemotherapy through the testing of dose and schedule, the value of adding novel agents, and the role of biological agents. Current and future projects are aimed at exploiting and increasing our growing knowledge of the molecular biology of breast cancer by developing targeted therapies. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1210, Boston, MA 02115 USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 SU S BP 3576S EP 3580S DI 10.1158/1078-0432.CCR-06-9016 PN 2 PG 5 WC Oncology SC Oncology GA 052IR UT WOS:000238227900005 PM 16740788 ER PT J AU Goldberg, RM Niedzwiecki, D Bertagnolli, M Blackstock, AW Tepper, JE Mayer, RJ AF Goldberg, RM Niedzwiecki, D Bertagnolli, M Blackstock, AW Tepper, JE Mayer, RJ TI Cancer and Leukemia Group B Gastrointestinal Cancer Committee SO CLINICAL CANCER RESEARCH LA English DT Article ID ADVANCED COLORECTAL-CARCINOMA; HOSPITAL PROCEDURE VOLUME; RESECTABLE COLON-CANCER; RECTAL-CANCER; ADJUVANT THERAPY; STROMAL TUMORS; PROMOTER HYPERMETHYLATION; FINAL REPORT; HIGH-RISK; MICROSATELLITE INSTABILITY AB The Cancer and Leukemia Group B Gastrointestinal Cancer Committee was organized in the late 1970s under the leadership of Michael Perry and Philip Schein and began full-scale operations in the mid-1980s. Today, it is a multidisciplinary team of surgeons, radiation and medical oncologists; statisticians, quality-of-life experts, pharmacogeneticists, basic scientists, and community oncologists who design studies that are conducted across the United States. The Committee has done trials in patients with esophageal, gastric, pancreatic, colon, rectal, and anal cancers., New initiatives are under way in hepatocellular cancer, cholangiocarcinoma, and neuroendocrine tumors originating in the gastrointestinal tract.,The Committee has increasingly concentrated on translational studies using tumor blocks, germ-line DNA, and plasma to evaluate biological correlates of tumor response and clinical outcomes. A broad program of pharmacogenomics has been incorporated for virtually all studies, including trials that prospectively use polymorphisms in drug-metabolizing genes to assign treatments. Future efforts aim to evolve new standards of care evaluate new therapies, and answer relevant biological questions in gastrointestinal cancer. C1 Univ N Carolina, Chapel Hill, NC 27599 USA. Duke Univ, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. RP Goldberg, RM (reprint author), Univ N Carolina, CB 7305, Chapel Hill, NC 27599 USA. RI Goldberg , Richard/M-1311-2013 NR 43 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 SU S BP 3589S EP 3595S DI 10.1158/1078-0432.CCR-06-9004 PN 2 PG 7 WC Oncology SC Oncology GA 052IR UT WOS:000238227900007 PM 16740790 ER PT J AU Small, EJ Halabi, S Kantoff, P D'Amico, A Stadler, W Kelley, WK Mohler, J Bajorin, D Vogelzang, NJ AF Small, EJ Halabi, S Kantoff, P D'Amico, A Stadler, W Kelley, WK Mohler, J Bajorin, D Vogelzang, NJ TI Activities and accomplishments of the Cancer and Leukemia Group B Genitourinary Committee SO CLINICAL CANCER RESEARCH LA English DT Article ID REFRACTORY PROSTATE-CANCER; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; PHASE-III TRIAL; PROGNOSTIC-SIGNIFICANCE; GROUP-B-9480; ESTRAMUSTINE; DOCETAXEL; CALGB-9583; MEN AB The Cancer and Leukemia Group B Genitourinary (GU) Committee has developed a multidisciplinary approach to treatment of GU cancer and has integrated correlative science research into the major research themes of the GU Committee; In localized prostate cancer,,trials, have evaluated novel approaches in radiation therapy. For patients with recurrence after local therapy, a trial evaluating local recurrence with salvage prostatectomy and a study of systemic therapy with peripheral androgen blockade" were undertaken. Major contributions have been made in, developing and testing therapeutics for advanced, androgen-independent prostate cancer (ketoconazole, suramin, estramustine/docetaxel,,and docetaxel/bevacizumab), and in developing predictive markers and algorithms to assess prognosis in these patients. Contributions in kidney cancer have included the development of novel trial methodology, such as the randomized discontinuation trial design, and the testing of antiangiogenics. In addition to these areas, future work of the committee will include further development of therapy for earlier-stage prostate cancer patients and bladder cancer patients. C1 Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94115 USA. Duke Univ, Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Chicago, IL 60637 USA. Yale Univ, New Haven, CT USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Nevada Canc Inst, Las Vegas, NV USA. RP Small, EJ (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, 1600 Divisadero St,Box 1711, San Francisco, CA 94115 USA. EM smaIle@medicine.ucsf.edu NR 22 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 SU S BP 3596S EP 3600S DI 10.1158/1078-0432.CCR-06-9005 PN 2 PG 5 WC Oncology SC Oncology GA 052IR UT WOS:000238227900008 PM 16740791 ER PT J AU Paskett, ED Schrag, D Kornblith, A Lamont, EB Weeks, JC Marshall, JR Shapiro, C Holland, J AF Paskett, ED Schrag, D Kornblith, A Lamont, EB Weeks, JC Marshall, JR Shapiro, C Holland, J TI Cancer and Leukemia Group B Cancer Control and Health Outcomes Committee: Origins and accomplishments SO CLINICAL CANCER RESEARCH LA English DT Article ID QUALITY-OF-LIFE; PREVENT COLORECTAL ADENOMAS; PSYCHOSOCIAL ADAPTATION; RANDOMIZED-TRIAL; BREAST-CANCER; PHASE-III; LUNG-CANCER; SURVIVORS; CHEMOTHERAPY; DISEASE AB Cancer and Leukemia Group B (CALGB) has conducted protocols in cancer prevention and control psycho-oncology, and health services for many years. Significant findings from the studies have emerged and have helped shape the practice of medicine and the,direction of future research in these areas. This article describes the origins of the Cancer Control and Health Outcomes Committee within CALGB and briefly describes significant findings and future work. The success CALGB has had with psycho-oncology and health services research has paved the way for other cooperative groups to develop these modalities. Cancer control research is growing and continues to gather momentum. This type of research is integral to providing quality care to patients and healthy populations. C1 Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Inst Technol Assessment, Boston, MA USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Paskett, ED (reprint author), Ohio State Univ, Ctr Comprehens Canc, A356 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [K07 CA093892] NR 26 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2006 VL 12 IS 11 SU S BP 3601S EP 3605S DI 10.1158/1078-0432.CCR-06-9006 PN 2 PG 5 WC Oncology SC Oncology GA 052IR UT WOS:000238227900009 PM 16740792 ER PT J AU Habib, GB AF Habib, GB TI Prevention of vascular events in patients with cerebrovascular disease: Efficacy and appropriate duration of antiplatelet therapy SO CLINICAL CARDIOLOGY LA English DT Review DE stroke; secondary prevention; extended-release dipyridamole; clopidogurel; antiplatelet ID TRANSIENT ISCHEMIC ATTACK; EUROPEAN STROKE PREVENTION; AMERICAN-HEART-ASSOCIATION; HIGH-RISK PATIENTS; RANDOMIZED TRIALS; 30 MG; ASPIRIN; CLOPIDOGREL; REHABILITATION; DIPYRIDAMOLE AB Antiplatelet therapy has shown consistent benefit in the prevention of secondary stroke. The paucity of head-to-head studies of different antiplatelet regimens, assessment of comparative efficacy, and optimal treatment duration requires evaluation and comparison of clinical studies that vary extensively in design and follow-up. Evidence for aspirin benefit in secondary stroke prevention is strong, but existing studies provide little guidance with regard to treatment duration. The efficacy of clopidogrel in secondary event prevention is significantly greater than that of aspirin for patients with a history of peripheral artery disease, but does not differ from that of aspirin for patients with a history of stroke or myocardial infarction. Relative to clopidogrel alone, the addition of aspirin to clopidogrel results in increased risk for life-threatening bleeding episodes similar in absolute magnitude to the reduction of secondary event risk in patients with stroke. Benefits associated with clopidogrel occur early in the course of therapy; few data support clopidogrel use for longer than I year after stroke. Monotherapy with extended-release dipytidamole (ER-DP) provides reduction in secondary stroke risk similar to aspirin; however, the combination of aspirin plus ER-DP significantly reduces risk relative to either agent alone. Compared with placebo and monotherapy with either agent, risk reduction for the aspirin plus ER-DP combination continued through 24 months, with no concomitant increase in bleeding risk. Additional clinical studies should provide needed comparisons of efficacy and guidance with regard to optimal duration of therapy. C1 Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. RP Habib, GB (reprint author), Michael E DeBakey vet Affairs Med Ctr, Cardiol Sect, Off 3C 310E, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM gabehabib@yahoo.com NR 19 TC 1 Z9 1 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUN PY 2006 VL 29 IS 6 BP 244 EP 248 DI 10.1002/clc.4960290604 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 048OT UT WOS:000237957100003 PM 16796073 ER PT J AU Kruse, L Mitchell, AM Camargo, CA Hernandez, J Kline, JA AF Kruse, L Mitchell, AM Camargo, CA Hernandez, J Kline, JA TI Frequency of thrombophilia-related genetic variations in patients with idiopathic pulmonary embolism in an urban emergency department SO CLINICAL CHEMISTRY LA English DT Article ID FACTOR-V-LEIDEN; DEEP-VEIN THROMBOSIS; VENOUS THROMBOEMBOLISM; RISK-FACTORS; PROTHROMBIN G20210A; REDUCTASE MTHFR; HOMOCYSTEINE; DIAGNOSIS; ETIOLOGY; POPULATION AB Background: The frequency of the thrombophilic genetic variants factor V Leiden (FVC) G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T in acutely symptomatic ambulatory patients with idiopathic pulmonary embolism (PE) has not been measured. Methods: This prospective case-control study included patients presenting to urban emergency departments (EDs) with chest pain or shortness of breath. Cases were classified as idiopathic PE (49 patients with PE, but without overt risk factors for thrombosis). Control groups included (a) patients with nonidiopathic PE (152 patients with PE and risk factors); (b) patients in whom PE was excluded (91 patients who had PE ruled out with a structured protocol, including follow-up); and (c) patients in whom PE was not suspected (193 patients without a workup for PE, who were free of PE on follow-up). Blood DNA extracts were analyzed by PCR and restriction fragment length polymorphism analysis for the FVL, prothrombin, and MTHFR sequence variations. Results: Either the FVL or prothrombin variant was found in 10% (95% confidence interval, 3%-22%) of patients with idiopathic PE compared with 13% (8%-20%) of nonidiopathic PE, 2% (5%-14%) of PE excluded, and 9% (5%-14%) of PE not suspected patients. Patients with idiopathic PE tended to have a higher frequency of homozygous MTHFR sequence variants, but mean (SD) plasma homocysteine concentrations were not increased [15.6 (5.4) mu mol/L vs 12.8 (4.6) mu mol/L for homozygous, and wild-type, respectively, P=0.40]. Conclusions: The frequency of either the FVL or prothrombin sequence variant was not increased in idiopathic PE patients compared with nonidiopathic PE patients or patients who had PE excluded. These data suggest that genotyping to detect idiopathic PE would have limited clinical utility in the urban ED setting. (c) 2006 American Association for Clinical Chemistry. C1 Carolinas Med Ctr, Dept Emergency Med, James G Cannon Res Ctr, Charlotte, NC 28203 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Kline, JA (reprint author), Carolinas Med Ctr, Dept Emergency Med, James G Cannon Res Ctr, Med Educ Bldg,3rd Floor,1000 Blythe Blvd, Charlotte, NC 28203 USA. EM Jeff.Kline@carolinashealthcare.org FU NHLBI NIH HHS [R01 HL074384] NR 37 TC 7 Z9 10 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2006 VL 52 IS 6 BP 1026 EP 1032 DI 10.1373/clinchem.2005.061861 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 047VY UT WOS:000237908000014 PM 16574759 ER PT J AU Grenier, F Ali, S Syed, H Ryan, W Sluss, PM Ming, L Pui-Yuen, W AF Grenier, F. Ali, S. Syed, H. Ryan, W. Sluss, P. M. Ming, L. Pui-Yuen, W. TI Multi-site evaluation of an assay in development for sirolimus on the abbott ARCHITECTO analyzer SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Clinical-Chemistry CY JUL 23-27, 2006 CL Chicago, IL SP Amer Assoc Clin Chem C1 Abbott Diagnost, Abbott Pk, IL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2006 VL 52 IS 6 SU S MA B112 BP A72 EP A73 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 048CT UT WOS:000237925900226 ER PT J AU Hermsen, D Apple, F Garcia-Beltran, L Jaffe, A Karon, B Lewandrowski, E Muhlbacher, A Muller, R Ordonez, J Pagani, F Panteghini, M Plecko, T Jarausch, J AF Hermsen, D. Apple, F. Garcia-Beltran, L. Jaffe, A. Karon, B. Lewandrowski, E. Muehlbacher, A. Mueller, R. Ordonez, J. Pagani, F. Panteghini, M. Plecko, T. Jarausch, J. TI Results from a multicenter evaluation of the 4th generation Elecsys (R) Troponin T assay SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Clinical-Chemistry CY JUL 23-27, 2006 CL Chicago, IL SP Amer Assoc Clin Chem C1 Univ Dusseldorf, Inst Clin Chem & Lab Diagnost, D-4000 Dusseldorf, Germany. Hennepin Cty Med Ctr, Dept Lab Med & Pathol, Minneapolis, MN 55415 USA. Hosp Gen Valle Hebron, Barcelona, Spain. Mayo Clin, Rochester, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Landesklin Blutgrp Serol & Transfus Med, Salzburg, Austria. Univ Klinikum Aachen, Inst Clin Chem, Aachen, Germany. Hosp Santa Creu & Sant Pau, Barcelona, Spain. Spedali Civil Brescia, Brescia, Italy. Univ Milan, Milan, Italy. Klinikum Stuttgart, Zent Klin Chem, Stuttgart, Germany. Klinikum Stuttgart, Lab Med, Stuttgart, Germany. Roche Diagnost GmbH, Penzberg, Germany. RI Ordonez-Llanos, Jordi/B-4961-2011 OI Ordonez-Llanos, Jordi/0000-0003-4896-5832 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2006 VL 52 IS 6 SU S MA D27 BP A130 EP A130 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 048CT UT WOS:000237925900403 ER PT J AU Sluss, PM Barnes, W Ramsay, CA Doss, RC Crowley, WF AF Sluss, P. M. Barnes, W. Ramsay, C. A. Doss, R. C. Crowley, W. F. TI Development, evaluation and LC/MS/MS comparison of an automated immunoassay for the determination of cortisol on the Abbott ARCHITECT Analyzer SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Clinical-Chemistry CY JUL 23-27, 2006 CL Chicago, IL SP Amer Assoc Clin Chem C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Abbott Diagnost, Abbott Pk, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2006 VL 52 IS 6 SU S MA C65 BP A99 EP A99 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 048CT UT WOS:000237925900307 ER PT J AU Sartor, O Loriaux, DL AF Sartor, Oliver Loriaux, D. Lynn TI The emotional burden of low-risk prostate cancer: Proposal for a change in nomenclature SO CLINICAL GENITOURINARY CANCER LA English DT Editorial Material ID ADENOCARCINOMA; SURGERY; ANTIGEN; SERUM C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. RP Sartor, O (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD JUN PY 2006 VL 5 IS 1 BP 16 EP 17 DI 10.3816/CGC.2006.n.013 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 112LI UT WOS:000242527000001 PM 16859573 ER PT J AU Oh, WK Hayes, J Evan, C Manola, J George, DJ Waldron, H Donovan, M Varner, J Orechia, J Katcher, B Lu, D Nevins, A Wright, RL Tormey, L Talcott, J Rubin, MA Loda, M Sellers, WR Richie, JP Kantoff, PW Weeks, J AF Oh, William K. Hayes, Julia Evan, Carolyn Manola, Judith George, Daniel J. Waldron, Helen Donovan, Meaghan Varner, John Orechia, John Katcher, Beth Lu, Diana Nevins, Arthur Wright, Renee L. Tormey, Lauren Talcott, James Rubin, Mark A. Loda, Massimo Sellers, William R. Richie, Jerome P. Kantoff, Philip W. Weeks, Jane TI Development of an integrated Prostate Cancer Research Information System SO CLINICAL GENITOURINARY CANCER LA English DT Article DE database; Gleason score; prostate-specific antigen ID DATABASE AB Background: In this article, we describe the design and implementation of a comprehensive prostate cancer database developed to collect, store, and access clinical, treatment, and outcomes data for research and clinical care. Patients and Methods: The Prostate Cancer Clinical Research Information System is a relational database. Data are entered from multiple sources, including medical records, institutional laboratory, patient registration, pharmacy systems, and clinician forms. The history, design, and operational characteristics of the database are described. Issues regarding necessary staffing and funding of databases are reviewed. Results: Four thousand two hundred forty-six patients have information in the Prostate Cancer Clinical Research Information System. Mean age of patients is 62 years, and 89% are white. Seventy-one percent of patients presented at diagnosis with T1 or T2 disease, and 78% had biopsy Gleason scores of <= 7, 8-10 in 18%. Median prostate-specific antigen level at diagnosis was 7 ng/mL, and 77% of patients presented with increased prostate-specific antigen as a trigger symptom. Sixty-four percent of patients presented to our clinic having had no previous treatment for prostate cancer. The majority of approached patients provided consent for collection of clinical data, blood, and tissue. Quality control assessments demonstrate high levels of concordance among data entry personnel. Conclusion: Clinical databases are difficult to implement and maintain; however, they represent a valuable resource, particularly when linked to blood and tissue banks. Elements needed for a successful clinical database include engagement of clinicians, utility for research, and the ability to integrate with legacy systems. As cancer centers develop such databases, lessons learned from each experience should be shared in order to optimize the process. C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Informat Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012; OI Oh, William/0000-0001-5113-8147; Rubin, Mark/0000-0002-8321-9950 NR 4 TC 41 Z9 41 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD JUN PY 2006 VL 5 IS 1 BP 61 EP 66 DI 10.3816/CGC.2006.n.019 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 112LI UT WOS:000242527000008 PM 16859581 ER PT J AU Zhou, YL Abdi, S AF Zhou, YL Abdi, S TI Diagnosis and minimally invasive treatment of lumbar discogenic pain - A review of the literature SO CLINICAL JOURNAL OF PAIN LA English DT Review DE low back pain; internal disc disruption; annular tear; discography ID LOW-BACK-PAIN; INTRADISCAL ELECTROTHERMAL THERAPY; HIGH-INTENSITY ZONE; RANDOMIZED CONTROLLED-TRIAL; INTERNAL DISC DISRUPTION; MESENCHYMAL STEM-CELLS; HERNIATED NUCLEUS PULPOSUS; HUMAN INTERVERTEBRAL DISC; RAMUS COMMUNICANS NERVE; NITRIC-OXIDE AB Diagnosis and treatment of lumbar discogenic pain due to internal disc disruption (IDD) remains a challenge. It accounts for 39% of patients with low back pain. The mechanism of discogenic pain remains unclear and its clinical presentation is atypical. Magnetic resonance imaging (MRI) can find high-intensity zone as an indirect indication of IDD. However, relative low sensitivity (26.7% to 59%) and high false-positive (24%) and false-negative (38%) rates reduce the value of MRI in screening for the existence of painful IDD. Provocative discography can provide unique information about the pain source and the morphology of the disc. It may also provide information for selecting appropriate treatment for the painful annular tear. Adjunctive therapies, including nonsteroidal anti-inflammatory drugs, physical therapy, rehabilitation, antidepressants, antiepileptics, and acupuncture, have been used for low back pain. The value of these treatments for discogenic pain is yet to be established. Intradiscal steroid injection has not been proved to provide long-term benefits. Intradiscal electrothermal therapy may offer some pain relief for a group of well-selected patients. No benefits have been found for the intradiscal radiofrequency thermocoagulation. A block in the ramus communicans may interfere with the transition of painful information from the discs to the central nervous system. Disc cell transplantation is in the experimental stage. It has the potential to become a useful tool for the prevention and treatment of discogenic pain. Minimally invasive treatments provide alternatives for discogenic pain with the appeal of cost-effectiveness and, possibly, less long-term side effects. However, the value of most of these therapies is yet to be established. More basic science and clinical studies are needed to improve the clinical efficacy of minimally invasive treatments. C1 Univ Florida, Lake City, FL 32055 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care,MGH Pain Ctr, Boston, MA USA. RP Zhou, YL (reprint author), Univ Florida, 1037 Highway 90 W, Lake City, FL 32055 USA. EM Yilizhoumd@yahoo.com NR 181 TC 39 Z9 44 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD JUN PY 2006 VL 22 IS 5 BP 468 EP 481 DI 10.1097/01.ajp.0000208244.33498.05 PG 14 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 050SL UT WOS:000238108400010 PM 16772802 ER PT J AU Jagsi, R Makris, A Goldberg, S Taghian, A AF Jagsi, R Makris, A Goldberg, S Taghian, A TI Intra-European differences in the radiotherapeutic management of breast cancer: A survey study SO CLINICAL ONCOLOGY LA English DT Article DE breast cancer; Europe; patterns of care; radiation; survey ID CARCINOMA IN-SITU; ADJUVANT CHEMOTHERAPY; POSTOPERATIVE RADIOTHERAPY; LOCOREGIONAL FAILURE; PREMENOPAUSAL WOMEN; CONSERVING THERAPY; RANDOMIZED-TRIAL; NORTH-AMERICA; IRRADIATION; MASTECTOMY AB Aims: To document and explain self-reported practices of the radiotherapeutic management of breast cancer within different European regions. Methods: An original survey questionnaire was developed to assess radiation oncologists' self-reported management of breast cancer. The questionnaire was distributed to physician members of the American Society for Therapeutic Radiology and Oncology and the European Society of Therapeutic Radiation Oncology. This paper presents the results of the comparative analysis of 702 responses from North America and 435 responses from Europe. Results: Several areas of variation are identified. These include the selection criteria for post-mastectomy radiation and radiation for ductal carcinoma in situ (DCIS). Variations are also seen in the management of regional lymph nodes after lumpectomy, and radiation dose and fractionation. Conclusions: Radiation oncologists within Europe vary in their self-reported practices for managing women with breast cancer. These differences may be rooted in deeper cultural differences and differences in the healthcare systems of different European countries. They may also reflect differences in the relative weight radiation oncologists place upon data generated within their own countries. These results support the need for co-operative group trials to provide evidence for more uniform treatment recommendations and policies. C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Vernon Hosp, Acad Oncol Unit, Northwood HA6 2RN, Middx, England. RP Taghian, A (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Massachusetts Gen Hosp, Cox 302,100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org OI Jagsi, Reshma/0000-0001-6562-1228 NR 26 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD JUN PY 2006 VL 18 IS 5 BP 369 EP 375 DI 10.1016/j.clon.2006.02.004 PG 7 WC Oncology SC Oncology GA 049AV UT WOS:000237988700001 PM 16817326 ER PT J AU Geller, JA Malchau, H Bragdon, C Greene, M Harris, WH Freiberg, AA AF Geller, Jeffrey A. Malchau, Henrik Bragdon, Charles Greene, Meridith Harris, William H. Freiberg, Andrew A. TI Large diameter femoral heads on highly cross-finked polyethylene - Minimum 3-year results SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-ARTHROPLASTY; MOLECULAR-WEIGHT POLYETHYLENE; LINKED POLYETHYLENE; ACETABULAR COMPONENTS; WEAR; DISLOCATION; REPLACEMENT; SIZE; OSTEOLYSIS; REPAIR AB Contemporary highly cross-linked polyethylenes have become the most widely used alternative bearing surfaces in total hip replacement and may be paired with large diameter femoral heads (> 32 mm) in patients considered to be at high risk for dislocation. We report on a prospective series of 42 patients (45 hips) who had total hip replacement using large diameter cobalt-chrome femoral heads articulating with a highly cross linked polyethylene after a minimum of 3 years followup (mean 3.3 years). At final followup, the final patient cohort showed excellent clinical results with no radiographic failures or episodes of loosening. There was no evidence of pelvic or femoral osteolysis. One patient sustained a dislocation due to a grossly malpositioned acetabular component necessitating early isolated acetabular revision. The average yearly steady state wear rate was -0.06 +/- 0.41 mm/year. The results of our short-term prospective series indicated total hip replacement with large femoral heads articulating with a highly cross linked polyethylene showed excellent wear characteristics and clinical results and could be considered in patients at increased risk for dislocation. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Columbia Presbyterian Dept Orthoped Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Malchau, H (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Orthopaed Biomech & Biomat Lab, 55 Fruit St,YAW 3, Boston, MA 02114 USA. EM hmalchau@partners.org NR 26 TC 69 Z9 70 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JUN PY 2006 IS 447 BP 53 EP 59 DI 10.1097/01.blo.0000218742.61624.80 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119OC UT WOS:000243020600011 PM 16741475 ER PT J AU Wang, FN Thirumangalathu, S Loeken, MR AF Wang, Fangnian Thirumangalathu, Shoba Loeken, Mary R. TI Establishment of new mouse embryonic stem cell lines is improved by physiological glucose and oxygen SO CLONING AND STEM CELLS LA English DT Article ID OXIDATIVE STRESS; TRANSCRIPTION FACTOR; IN-VITRO; GENE-EXPRESSION; DEATH; BLASTOCYSTS; APOPTOSIS; DIFFERENTIATION; HYPERGLYCEMIA; C57BL/6 AB Embryonic stem cell lines are routinely selected and cultured in glucose and oxygen concentrations that are well above those of the intrauterine environment. Supraphysiological glucose and hyperoxia each increase oxidative stress, which could be detrimental to survival in vitro by inhibiting proliferation and/or inducing cell death. The aim of this study was to test whether isolation of new embryonic stem cell lines from murine blastocysts is improved by culture in physiological (5%) oxygen instead of approximately 20%, the concentration of oxygen in room air, or in media containing physiological (100 mg/dL) instead of. 450 mg/dL glucose. We found that culturing in either physiological oxygen or physiological glucose improved the success of establishing new murine embryonic stem cell lines, and that culture when concentrations of both oxygen and glucose were physiological improved the success of establishing new lines more than culture in either alone. Physiological oxygen and glucose reduce oxidative stress, as determined by 2',7'-dichloro-dihydrofluorescein fluorescence. BrdU incorporation suggests that physiological oxygen and glucose increase the pool of proliferating cells. Cells isolated in physiological oxygen and glucose are capable of self-renewal and differentiation into all three germ layers in vitro. However, none of the culture conditions prevents cytogenetic instability with prolonged passage. These results suggest that culture of cells derived from murine blastocysts in physiological oxygen and glucose reduces oxidant stress, which increases the success of establishing new embryonic stem cell lines. C1 Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.loeken@joslin.harvard.edu FU NIDDK NIH HHS [DK 58300] NR 47 TC 25 Z9 25 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2302 J9 CLONING STEM CELLS JI Cloning Stem Cells PD SUM PY 2006 VL 8 IS 2 BP 108 EP 116 DI 10.1089/clo.2006.8.108 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Genetics & Heredity SC Cell Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 060LN UT WOS:000238803800005 PM 16776602 ER PT J AU Maytal, G Ostacher, M Stern, TA AF Maytal, G Ostacher, M Stern, TA TI Aripiprazole-related tardive dyskinesia SO CNS SPECTRUMS LA English DT Article ID ATYPICAL ANTIPSYCHOTICS; SCHIZOPHRENIA; OLANZAPINE; MANAGEMENT AB The low prevalence of extrapyramidal symptoms associated with atypical antipsychotics has led to their widespread use during the past decade. Aripiprazole, the newest medication in this class, has been associated with extrapyramidal symptoms (eg, akathisia) and with improvement of tardive dyskinesia (TD), but to date it has not been associated with the development of TD. We report a case of TD associated with the use of aripiprazole 15 mg/day for 18 months for refractory depression. Symptoms of TD resolved within several weeks of discontinuation of aripiprazole. C1 Massachusetts Gen Hosp, Psychiat Consultat Serv, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Maytal, G (reprint author), Massachusetts Gen Hosp, Psychiat Consultat Serv, 55 Fruit St,Warren Bldg,Room 605, Boston, MA 02114 USA. EM gmaytal@partners.org OI Ostacher, Michael/0000-0003-0353-7535 NR 27 TC 27 Z9 28 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD JUN PY 2006 VL 11 IS 6 BP 435 EP + PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 057PL UT WOS:000238607600010 PM 16816781 ER PT J AU Verfaellie, M Martin, E Page, K Parks, E Keane, MM AF Verfaellie, Mieke Martin, Elizabeth Page, Katie Parks, Elizabeth Keane, Margaret M. TI Implicit memory for novel conceptual associations in amnesia SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article ID RECOGNITION MEMORY; ITEM RECOGNITION; HIPPOCAMPAL; INFORMATION; DISSOCIATIONS; MECHANISMS; DEFICITS; INTACT; SINGLE; FMRI AB In two experiments, we evaluated the status of implicit memory for novel associations in amnesia. Experiment 1 assessed priming in a category exemplar generation task in which contextual information associated with a target could increase the likelihood of target generation. Control participants, but not amnesic patients, showed associative priming. Amnesics' impairment was not due to the use of explicit memory by control subjects but reflected a genuine impairment in implicit memory for novel conceptual associations. Experiment 2 assessed printing in a relatedness judgment task, in which associative printing was manifest as longer latencies for old than for recombined pairs of unrelated words. Amnesic patients showed intact associative priming in this task. We discuss differences in the status of implicit memory for novel conceptual associations in amnesia, with reference to the nature of the representation that supports priming in the two tasks and the type of processing that is required at test. C1 Boston Dept Vet Affairs, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Wellesley Coll, Wellesley, MA 02181 USA. RP Verfaellie, M (reprint author), Memory Disorders Res Ctr, Boston VA Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM verf@bu.edu FU NIMH NIH HHS [R01 MH057681, MH57681]; NINDS NIH HHS [P50 NS026985, NS26985] NR 41 TC 14 Z9 15 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD JUN PY 2006 VL 6 IS 2 BP 91 EP 101 DI 10.3758/CABN.6.2.91 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 084EW UT WOS:000240516000001 PM 17007230 ER PT J AU Verfaellie, M Giovanello, KS AF Verfaellie, M Giovanello, KS TI Conceptual priming in semantic dementia: A window into the cognitive and neural basis of conceptual implicit memory SO COGNITIVE NEUROPSYCHOLOGY LA English DT Article ID INFERIOR PREFRONTAL CORTEX; WORD GENERATION; ALZHEIMERS-DISEASE; FUNCTIONAL MRI; REPETITION; KNOWLEDGE; IMPAIRMENT; PATIENT; MODEL; RETRIEVAL AB The present study examined the impact of impairment in semantic memory on conceptual repetition priming by means of the longitudinal study of a patient with semantic dementia. ST was tested in four consecutive years, during which his semantic memory progressively deteriorated. On each occasion, he performed an abstract/concrete verification task and a verb generation task. In both of these tasks, performance during a test phase was compared for stimuli previously processed in a study phase and stimuli first seen in the test phase. Control subjects showed priming, as indicated by faster responses to studied than to baseline stimuli. ST showed intact priming that was of normal magnitude in the first two years of testing, but failed to show priming in the subsequent two years of testing. This pattern of results is interpreted with reference to the differential decline of item-specific and super-ordinate knowledge. The implications of these findings for the neural basis of conceptual priming are also discussed. C1 Memory Disorders Res Ctr, Boston VA Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. Harvard Univ, Boston, MA 02115 USA. RP Verfaellie, M (reprint author), Memory Disorders Res Ctr, Boston VA Healthcare Syst, 151A,150 S Huntington Ave, Boston, MA 02130 USA. EM verf@bu.edu OI Verfaellie, Mieke/0000-0001-5535-4584 NR 41 TC 2 Z9 2 U1 3 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PD JUN PY 2006 VL 23 IS 4 BP 606 EP 620 DI 10.1080/02643290500346099 PG 15 WC Psychology; Psychology, Experimental SC Psychology GA 049BI UT WOS:000237990000005 PM 21049346 ER PT J AU Yu, EN Jurkunas, U Rubin, PAD Baltatzis, S Foster, CS AF Yu, EN Jurkunas, U Rubin, PAD Baltatzis, S Foster, CS TI Obliterative microangiopathy presenting as chronic conjunctivitis in a patient with relapsing polychondritis SO CORNEA LA English DT Article DE relapsing polychondritis; chronic conjunctivitis; methotrexate; microangiopathy; vasculitis AB Purpose: To report histopathologic findings and treatment of obliterative microangiopathy in a patient with chronic conjunctivitis due to relapsing polychondritis (RP). Methods: This interventional case report describes a 50-year-old woman with relapsing polychondritis was referred to the Ocular Immunology and Uveitis Service for bilateral tearing due to refractory chronic conjunctivitis. Ocular examination revealed the presence of bilateral follicular conjunctivitis. Conjunctival biopsy of the inferior palpebral conjunctiva was performed, and the histopathologic findings guided the therapeutic intervention. Results: The pathology of the conjunctival biopsy included granulomatous obliterative microangiopathy with numerous eosinophils, plasma cells, lymphocytes, and epithelioid cells in the substantia propia. The chronic conjunctivitis resolved with systemic methotrexate therapy. Conclusions: Microangiopathy may cause chronic conjunctivitis in patients with RP and may be a harbinger of evolving nonocular problems as a consequence of incomplete control of this autoimmune disorder. Immunomodulatory therapy should be considered in such cases to prevent possible cardiovascular, renal, respiratory, and neurologic complications of vasculitis. Although methotrexate has been used in treatment of RP-related necrotizing scleritis with poor results, it can be sufficient for the conjunctivitis with microangiopathy associated with RP. C1 Harvard Univ, Sch Med, Massachusetts Eye & Res & Surg Inst, Ocular Immunol & Uveitis Fdn, Boston, MA 02115 USA. St Lukes Hosp, Uveitis Serv, Quezon City, Philippines. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Foster, CS (reprint author), Massachusetts Eye & Res & Surg Inst, Cambridge Ctr 5, Cambridge, MA 02142 USA. EM fosters@uveitis.org NR 4 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUN PY 2006 VL 25 IS 5 BP 621 EP 622 DI 10.1097/01.ico.0000227886.26747.a9 PG 2 WC Ophthalmology SC Ophthalmology GA 058PO UT WOS:000238677100021 PM 16783155 ER PT J AU Sitaula, R Bhowmick, S AF Sitaula, R Bhowmick, S TI Moisture sorption characteristics and thermophysical properties of trehalose-PBS mixtures SO CRYOBIOLOGY LA English DT Article DE desorption isotherm; water activity; glass transition temperature; crystallization; trehalose; phosphate-buffered saline; Fourier transform infrared spectroscopy; differential scanning calorimetry ID WATER-VAPOR ABSORPTION; AMORPHOUS PHARMACEUTICAL SOLIDS; CELLS; ISOTHERMS; STARCH; SUGAR; STATE; STABILIZATION; PRESERVATION; TEMPERATURE AB The goal of the study was to quantify the thermophysical properties and the moisture sorption characteristics of the trehalose-PBS (phosphate-buffered saline) from the desiccation preservation perspective. A moisture sorption study was undertaken to determine the desorption isotherms of the trehalose-PBS mixtures. The Brunauer, Emmett, and Teller (BET)-equation and the Guggenheim, Anderson, and de Boer equation were used to quantify the desorption data. The glass transition temperature of the mixtures of trehalose PBS, equilibrated at different relative humidities was studied using a differential scanning calorimeter. Fourier transform infrared spectroscopy was used to study the molecular interaction between the trehalose and PBS mixtures. The results showed that the addition of PBS to the trehalose mixture causes a shift from the type II isotherm to a type III isotherm (characterized by BET equation) which may have detrimental effect on cell desiccation. The results showed that an increase in PBS mass fraction in the trehalose-PBS mixture causes a decrease in the Glass transition temperature (T-g) of the mixture and also a decrease in the hydrogen bonding capacity of the trehalose glasses. The addition of PBS to trehalose posed some challenges and should be subject to further optimization to use it in desiccation preservation of biologics. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. RP Bhowmick, S (reprint author), Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. EM sbhowmick@umassd.edu NR 36 TC 7 Z9 8 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD JUN PY 2006 VL 52 IS 3 BP 369 EP 385 DI 10.1016/j.cryobiol.2006.01.006 PG 17 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 051OE UT WOS:000238169600006 PM 16545359 ER PT J AU Shah, K Breakefield, XO AF Shah, Khalid Breakefield, Xandra O. TI HSV amplicon vectors for cancer therapy SO CURRENT GENE THERAPY LA English DT Review DE oncolytic virus; anti-angiogenesis; prodrug activation; immune enhancement; apoptosis; RNAi; AAV; HSV; retrovirus ID SIMPLEX-VIRUS TYPE-1; POSITRON-EMISSION-TOMOGRAPHY; EPSTEIN-BARR-VIRUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; SITE-SPECIFIC INTEGRATION; HUMAN GLIOMA-CELLS; GENOMIC DNA LOCI; IN-VIVO; GENE-EXPRESSION; THYMIDINE KINASE AB HSV amplicon vectors provide a unique tool in the armamentarium of weapons for treatment of cancer. Their large capacity (up to 150 kb) allows incorporation of multiple and large transgenes, including whole gene loci, as well as components of other viruses to control the fate of transgenes in the host cells. Means have been developed to achieve heritable transmission of transgenes in tumor cells by episomal replication or genomic integration. Therapeutic transgenes incorporated into amplicon vectors have included anti-angiogenic agents, immune enhancing proteins. prodrug activating enzymes, and apoptosis-inducing factors, as well as inhibitory RNAs for tumor-associated messages. Perks of this vector system include the ability to combine amplicon vectors with oncolytic HSV recombinant vectors to extend the therapeutic range and to target non-dividing as well as dividing tumor cells. Tumor vaccination is favored by the high infectivity of dendritic antigen-presenting cells with HSV vectors, and the vectors themselves appear to have intrinsic immune enhancing properties. Promoter manipulation can be used to target therapeutic gene expression to specific tumor cell types and to achieve drug regulated transgene expression. Further, amplicon vectors can be used to convert tumor cells into packaging cells for retrovirus and adeno-associated virus vectors, thus generating vectors on site. Amplicon vectors have also proven to be a versatile tool to explore imaging modalities to monitor gene delivery and tumor responses to therapeutic intervention. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Shah, K (reprint author), Massachusetts Gen Hosp, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM kshah@helix.mgh.harvard.edu FU NCI NIH HHS [CA86355, CA69426] NR 88 TC 15 Z9 16 U1 2 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5232 J9 CURR GENE THER JI Curr. Gene Ther. PD JUN PY 2006 VL 6 IS 3 BP 361 EP 370 DI 10.2174/156652306777592063 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 064IR UT WOS:000239083000008 PM 16787187 ER PT J AU Levine, WC Mehta, V Landesberg, G AF Levine, Wilton C. Mehta, Vipin Landesberg, Giora TI Anesthesia for the elderly: selected topics SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Article DE cognitive dysfunction; diastolic dysfunction; prophylactic beta-blockade AB Purpose of review With the graying of the Western population, there is a continuous increase in the proportion of elderly patients undergoing surgical procedures. Geriatric anesthesia is emerging from a 'subspecialty' to the mainstream of today's anesthesia and perioperative care. Much has been written on anesthesia for the elderly, but this review will concentrate on selected topics related to elderly care that represent current unresolved and pertinent issues for the care of the elderly surgical patient. Recent findings Postoperative cognitive dysfunction, cardiac diastolic dysfunction and prophylactic perioperative beta-blockade in the process of major noncardiac surgery are three main topics that have recently attracted great interest in clinical practice and research, and have therefore been chosen as the selected topics for this current review. Summary Although age is a clear risk factor for postoperative cognitive dysfunction, the association of general anesthesia with cognitive dysfunction is less clear, as is the effect of anesthesia per se or surgery on long-term cognitive dysfunction. Cardiac diastolic dysfunction is a relatively new and evolving concept in anesthesia and perioperative medicine, yet clearly diastolic dysfunction even with a normal ejection fraction may have a significant effect on the perioperative outcome and management of elderly patients. Small, but powerful studies have shown significant outcome benefit with prophylactic perioperative beta-blockade in high-risk patients undergoing major noncardiac surgery. Data from other studies, however, are still conflicting and the final verdict awaits larger scale outcome studies. C1 [Levine, Wilton C.; Mehta, Vipin; Landesberg, Giora] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Landesberg, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM gio@cc.huji.ac.il NR 39 TC 14 Z9 15 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0952-7907 EI 1473-6500 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD JUN PY 2006 VL 19 IS 3 BP 320 EP 324 DI 10.1097/01.aco.0000192807.63785.59 PG 5 WC Anesthesiology SC Anesthesiology GA V42RX UT WOS:000209632000016 PM 16735817 ER PT J AU Sanchez-del-Rio, M Reuter, U Moskowitz, MA AF Sanchez-del-Rio, M Reuter, U Moskowitz, MA TI New insights into migraine pathophysiology SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE cortical spreading depression; genetics; migraine aura; prevention ID FAMILIAL HEMIPLEGIC MIGRAINE; CORTICAL SPREADING DEPRESSION; SODIUM-CHANNEL SCN1A; POSSIBLE MECHANISM; HEADACHE; AURA; TOPIRAMATE; MUTATION; CORTEX; TYPE-2 AB Purpose of review This article will review new and exciting developments in migraine research, with particular emphasis on mutations I associated with familial hemiplegic migraine and the role depression in its pathophysiology and cortical spreading treatment. Recent findings The recent discovery of multiple point mutations in familial hemiplegic migraine has led to the suggestion that migraine and its van ants may be due to a paroxysmal disturbance in ion-translocating mechanisms. Mutations associated with familial hemiplegic migraine render the brain more susceptible to prolonged cortical spreading depression, caused by either excessive synaptic glutamate release or decreased removal of glutamate and potassium from the synaptic cleft, or persistent sodium influx. Suppression of cortical spreading depression has become an interesting target for preventive migraine treatment. Prolonged treatment with beta-blockers, valproate, topiramate, methysergide or amitriptyline reduced the number of potassium-evoked cortical spreading depressions and elevated the electrical stimulation threshold for the induction of cortical spreading depression in rats. Recent imaging studies in patients suffering from migraine without, aura also point to the presence of silent cortical spreading depression as an underlying mechanism. Repeated waves of cortical spreading depression may have deleterious effects on brain function, and perhaps cause silent ischaemic lesions in vulnerable brain regions such as the cerebellum in susceptible individuals. Summary This review emphasizes several neurobiological aspects of migraine that reveal paroxysmal disturbances in neuronal and vascular function, that in turn reflect disturbances in the maintenance of ionic gradients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. Hosp Ruber Int, Dept Neurol, Madrid, Spain. Univ Med Berlin, Charite, Dept Neurol, Berlin, Germany. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM Moskowitz@helix.mgh.harvard.edu RI Moskowitz, Michael/D-9916-2011 NR 36 TC 64 Z9 67 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD JUN PY 2006 VL 19 IS 3 BP 294 EP 298 DI 10.1097/01.wco.0000227041.23694.5c PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 054BT UT WOS:000238351400011 PM 16702838 ER PT J AU Fallat, ME Donahoe, PK AF Fallat, Mary E. Donahoe, Patricia K. TI Intersex genetic anomalies with malignant potential SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE androgen insensitivity syndrome; androgen receptors; gonadectomy; intersex; laproscopy; mixed gonadal dyysgenesis; pure gonadal dysgenesis; SRY gene; testicular carcinoma; Turner's syndrome; WT1 gene; Wilms tumor AB Purpose of review Mutations in genes contributing to sexual determination and differentiation can cause clinical syndromes with potential for the development of malignant tumors. This article focuses on intersex disorders requiring surveillance for and/or operation to prevent or treat malignancies. Recent findings Classification of intersex disorders into risk groups gives guidance to physicians about children who are vulnerable to malignant degeneration of the gonads or kidneys. The gonads most at risk are both dysgenetic and intra-abdominal, and early gonadectomies are recommended as malignancies have been reported in infancy. Predominant risk group include syndromes of gonadal dysgenesis and Ullrich Turner syndrome. Partial gonadectomy is feasible in true hermaphrodites commensurate with sex of rearing. Histologically normal intra-abdominal gonads may be left through puberty (androgen insensitivity syndromes). A palpably normal descended gonad in a child with a Y chromosome can be observed if the child is reared as male. Certain intersex syndromes with splice variants of the WT1 gene are susceptible of Wilms' tumors (Frasier and Denys-Drash syndromes). Summary Prevention or early recognition of malignancy in intersex disorders requires knowledge of the risk factors including dysgenetic gonads, a Y chromosome with intra-abdominal gonads and dysgenetic syndromes with WT1 gene splice variants. This paper describes the evolution toward laparoscopic gonadectomy in intersex patients as a means to remove abnormal gonads and associated ductal structures as dictated by the disease or syndrome. C1 [Fallat, Mary E.] Univ Louisville, Kosair Childrens Hosp, Dept Surg, Louisville, KY 40202 USA. [Donahoe, Patricia K.] Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. RP Fallat, ME (reprint author), Univ Louisville, Kosair Childrens Hosp, Dept Surg, 233 E Gray St,Ste 708, Louisville, KY 40202 USA. EM mefall01@louisville.edu NR 36 TC 24 Z9 26 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD JUN PY 2006 VL 18 IS 3 BP 305 EP 311 DI 10.1097/01.mop.0000193316.60580.d7 PG 7 WC Pediatrics SC Pediatrics GA V63FM UT WOS:000204273000015 PM 16721154 ER PT J AU Raut, CP Kulke, MH Glickman, JN Swanson, RS Ashley, SW AF Raut, Chandrajit P. Kulke, Matthew H. Glickman, Jonathan N. Swanson, Richard S. Ashley, Stanley W. TI Carcinoid tumors - In brief SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID PHASE-II TRIAL; HEPATIC ARTERIAL CHEMOEMBOLIZATION; COMPARATIVE GENOMIC HYBRIDIZATION; METASTATIC NEUROENDOCRINE TUMORS; ENDOCRINE GASTROENTEROPANCREATIC TUMORS; RADIOLABELED SOMATOSTATIN ANALOG; ENTEROCHROMAFFIN-LIKE CELL; APPETITE-SUPPRESSANT DRUGS; HUMAN-LEUKOCYTE INTERFERON; ENDOTHELIAL GROWTH-FACTOR C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Raut, CP (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 252 TC 18 Z9 18 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0011-3840 J9 CURR PROB SURG JI Curr. Probl. Surg. PD JUN PY 2006 VL 43 IS 6 BP 383 EP 450 DI 10.1067/j.cpsurg.2006.03.002 PG 68 WC Surgery SC Surgery GA 061UT UT WOS:000238899000002 PM 16781906 ER PT J AU Zhao, WG Valencia, AZ Melby, PC AF Zhao, Weiguo Valencia, Anais Z. Melby, Peter C. TI Biological activity of hamster interferon-gamma is modulated by the carboxyl-terminal tail SO CYTOKINE LA English DT Article DE interferon-gamma; hamster; Mesocricetus auratus; antiviral ID NUCLEAR-LOCALIZATION SEQUENCE; MOLECULAR PHYLOGENY; IFN-GAMMA; RECEPTOR; EXPRESSION; TRANSLOCATION; PEPTIDE; RODENTS; BINDING; CLONING AB The Syrian golden hamster (Mesocricetus auratus) is highly susceptible to a number of intracellular pathogens. Interferon-gamma (IFN-gamma), the primary macrophage-activating cytokine, plays a key role in the host defense against intracellular pathogens. The hamster IFN-gamma cDNA encodes a 174 amino acid protein that has an additional 17 amino acids at the carboxyl-terminus compared to IFN-gamma of mice and rats. A homologous C-terminal tail is also found in other non-murine rodents. The biological activity of hamster IFN-gamma had not been investigated previously so we first demonstrated the activity of native IFN-gamma in assays of IFN-gamma-induced receptor signaling and antiviral activity against vesicular stomatitis virus. We then tested the hypothesis that the C-terminal tail of hamster IFN-gamma could influence its biological activity. A truncated hamster IFN-gamma, in which the C-terminal 17 aa were removed by insertion of a stop codon at the position corresponding to the stop codon in the mouse sequence, had approximately 10-fold greater activity than the full length protein when measured in the two bioassays. Polyclonal and monoclonal anti-hamster IFN-gamma antibodies specifically inhibited this biological activity. Collectively, these data indicate that this unique structural feature influences the biological activity of hamster IFN-gamma. (c) 2006 Elsevier Ltd. All rights reserved. C1 S Texas Vet Hlth Care syst, Dept Vet Affairs, Med Ctr, Res Serv, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. RP Melby, PC (reprint author), S Texas Vet Hlth Care syst, Dept Vet Affairs, Med Ctr, Res Serv, 7400 Merton Minter Dr Mailstop 151, San Antonio, TX 78229 USA. EM melby@uthscsa.edu FU NCRR NIH HHS [RR14269] NR 25 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUN PY 2006 VL 34 IS 5-6 BP 243 EP 251 DI 10.1016/j.cyto.2006.05.006 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 084MI UT WOS:000240536700002 PM 16843003 ER PT J AU Ciocon, D Gowrishankar, T Herndon, T Kimball, AB AF Ciocon, D Gowrishankar, T Herndon, T Kimball, AB TI How low should you go: Novel device for nail trephination SO DERMATOLOGIC SURGERY LA English DT Article ID SUBUNGUAL HEMATOMAS; CHILDREN; REPAIR AB BACKGROUND The most commonly used treatment for subungual hematomas is nail trephination, a technique that is not standardized and that poorly controls for trephination depth. OBJECTIVE The objective was to test the safety and tolerance of a new device for nail trephination that uses innovative "mesoscission" or microcutting technology to create holes of specific depths in the nail plate without penetrating the nail bed. MATERIALS AND METHODS Fourteen adult subjects with healthy toenails had five holes drilled in a random single-blind fashion at different test settings into their right great toenail with this device and were assessed for pain and pressure tolerance as well as perioperative and postoperative complications. RESULTS Nail trephination with this device in this small pilot study was controlled and well tolerated. LIMITATIONS The study population was small (n=14) and the follow-up evaluation relied on patient self-report, which is not always reliable. The follow-up period was only 1 week and did not allow for evaluation of permanent nail plate deformity. CONCLUSION Mesoscission may be a controlled and practical alternative to traditional nail trephining methods. Path Scientific, LLC (Carlisle, MA) provided the equipment and 100% of the funding for this study. Dr. Ciocon and Dr. Kimball are affiliated with the Department of Dermatology, Brigham and Women's Hospital (Boston, MA). Neither has any financial relationship with Path Scientific. Dr. Gowrishankar is an employee of Path Scientific but has no financial interests in the company. Terry Herndon is President of Path Scientific, LLC, and provides 100% of funding for its costs. He is the owner and inventor of the PathFormer device. C1 Brigham & Womens Hosp, Dept Dermatol, Clin Unit Res Trials Skin, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Path Sci, LLC, Carlisle, MA USA. RP Kimball, AB (reprint author), Brigham & Womens Hosp, Dept Dermatol, Clin Unit Res Trials Skin, 221 Longwood Ave, Boston, MA 02115 USA. EM harvardskinstudies@partners.org NR 13 TC 9 Z9 10 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD JUN PY 2006 VL 32 IS 6 BP 828 EP 833 DI 10.1111/j.1524-4725.2006.32168.x PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 049FD UT WOS:000238000400009 PM 16792649 ER PT J AU Pyati, UJ Cooper, MS Davidson, AJ Nechiporuk, A Kimelman, D AF Pyati, UJ Cooper, MS Davidson, AJ Nechiporuk, A Kimelman, D TI Sustained Bmp signaling is essential for cloaca development in zebrafish SO DEVELOPMENT LA English DT Article DE Bmp signaling; transgenic zebrafish; ventral mesoderm; cloaca; proctodeum; excretory system; anus; anorectal ID HOMEOBOX GENES; POSTERIOR MESODERM; EXPRESSION; EMBRYOS; XENOPUS; DORSAL; VASCULOGENESIS; GASTRULATION; INDUCTION; SPADETAIL AB Bone morphogenetic protein ( Bmp) signaling has long been known to be important for the early development of the ventral mesoderm, including blood, vasculature and kidney cells. Although Bmp genes are continually expressed in the ventral cells throughout gastrulation and somitogenesis, previous studies in zebrafish have not addressed how the role of Bmp signaling changes over time to regulate ventral mesoderm development. Here, we describe the use of a transgenic inducible dominant-negative Bmp receptor line to examine the temporal roles of Bmp signaling in ventral mesoderm patterning. Surprisingly, we find that Bmp signaling from the mid-gastrula stage through early somitogenesis is important for excluding blood and vascular precursors from the extreme ventral mesoderm, and we show that this domain is normally required for development of the cloaca ( the common gut and urogenital opening). Using a novel assay for cloacal function, we find that larvae with reduced mid-gastrula Bmp signaling cannot properly excrete waste. We show that the cloacal defects result from alterations in the morphogenesis of the cloaca and from changes in the expression of genes marking the excretory system. Finally, we show that HrT, a T-box transcription factor, is a Bmp-regulated gene that has an essential function in cloacal development. We conclude that sustained Bmp signaling plays an important role in specification of the zebrafish cloaca by maintaining the fate of extreme ventral cells during the course of gastrulation and early somitogenesis. Furthermore, our data suggest that alterations in Bmp signaling are one possible cause of anorectal malformations during human embryogenesis. C1 Univ Washington, Dept Biochem, Seattle, WA 98195 USA. Univ Washington, Dept Biol, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. RP Kimelman, D (reprint author), Univ Washington, Dept Biochem, Box 357350, Seattle, WA 98195 USA. EM kimelman@u.washington.edu FU NIGMS NIH HHS [GM07270] NR 45 TC 51 Z9 53 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN 1 PY 2006 VL 133 IS 11 BP 2275 EP 2284 DI 10.1242/dev.02388 PG 10 WC Developmental Biology SC Developmental Biology GA 041QW UT WOS:000237471800019 PM 16672335 ER PT J AU Macia, E Ehrlich, M Massol, R Boucrot, E Brunner, C Kirchhausen, T AF Macia, E Ehrlich, M Massol, R Boucrot, E Brunner, C Kirchhausen, T TI Dynasore, a cell-permeable inhibitor of dynamin SO DEVELOPMENTAL CELL LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; COATED VESICLE FORMATION; TEMPERATURE-SENSITIVE MUTANT; EPIDERMAL-GROWTH-FACTOR; GTPASE DOMAIN MUTANTS; REVERSIBLE BLOCKAGE; MEMBRANE RETRIEVAL; PLASMA-MEMBRANE; MOLECULAR MOTOR; CHOLERA-TOXIN AB Dynamin is essential for clathrin-dependent coated vesicle formation. It is required for membrane budding at a late stage during the transition from a fully formed pit to a pinched-off vesicle. Dynamin may also fulfill other roles during earlier stages of vesicle formation. We have screened about 16,000 small molecules and have identified 1, named here dynasore, that interferes in vitro with the GTPase activity of dynamin1, dynamin2, and Drp1, the mitochondrial dynamin, but not of other small GTPases. Dynasore acts as a potent inhibitor of endocytic pathways known to depend on dynamin by rapidly blocking coated vesicle formation within seconds of dynasore addition. Two types of coated pit intermediates accumulate during dynasore treatment, U-shaped, half formed pits and O-shaped, fully formed pits, captured while pinching off. Thus, dynamin acts at two steps during clathrin coat formation; GTP hydrolysis is probably needed at both steps. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. CBR Inst Biomed Res Inc, 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 [GM03548, GM075252, GM62566-05] NR 54 TC 958 Z9 971 U1 8 U2 65 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2006 VL 10 IS 6 BP 839 EP 850 DI 10.1016/j.devcel.2006.04.002 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 052PD UT WOS:000238244700017 PM 16740485 ER PT J AU Shimeld, SM Levin, M AF Shimeld, SM Levin, M TI Evidence for the regulation of left-right asymmetry in Ciona intestinalis by ion flux SO DEVELOPMENTAL DYNAMICS LA English DT Article DE asymmetry; Pitx; ion pump; Ciona; protochordate; evolution ID LEFT-RIGHT AXIS; NODAL FLOW; SYMMETRY-BREAKING; ZEBRAFISH EMBRYO; KUPFFERS VESICLE; SITUS-INVERSUS; H+/K+-ATPASE; MICE; MEMBRANE; MOUSE AB Vertebrate embryos develop distinct left-right asymmetry under the control of a conserved pathway involving left-sided deployment of the nodal and Pitx2 genes. The mechanism that initiates asymmetric expression of these genes is less clear, with cilia, ion flux, and signalling molecules all implicated. Vertebrates share the chordate phylum with urochordates such as the sea squirt Ciona intestinalis. We have explored the role of ion flux in regulating left-right asymmetry in Ciona, using an assay in which perturbation of left-sided Ci-Pitx expression provides a read-out for the disruption of asymmetry. Our data show that omeprazole, which specifically inhibits H(+)K(+)ATPase activity, disrupts asymmetry in Ciona. The vertebrate H(+)K(+)ATPase is composed of two subunits, alpha and beta. We identified one Ciona beta ortholog and two Ciona alpha orthologs of the vertebrate H(+)K(+)ATPase genes, and show that one of these is expressed in dorsal and ventral embryonic midline cells shortly before the activation of left-sided Ci-Pitx expression. Furthermore, we show that omeprazole exerts its effect on asymmetry at this point in development, and additionally implicate K+ channels in the regulation of asymmetry in Ciona. These experiments demonstrate a role for ion flux in the regulation of asymmetry in Ciona, and show a conserved, ancestral role for the H(+)K(+)ATPase ion pump in this process. C1 Univ Oxford, Dept Zool, Oxford OX1 3PS, England. Harvard Univ, Sch Med, Cytokine Biol Dept, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dev & Craniofacial Biol Dept, Boston, MA 02115 USA. RP Shimeld, SM (reprint author), Univ Oxford, Dept Zool, Tinbergen Bldg,S Parks Rd, Oxford OX1 3PS, England. EM sebastian.shimeld@zoo.ox.ac.uk OI Shimeld, Sebastian/0000-0003-0195-7536 FU NIGMS NIH HHS [1-R01-GM-06227]; PHS HHS [RSG-02-04601] NR 49 TC 41 Z9 42 U1 3 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 2006 VL 235 IS 6 BP 1543 EP 1553 DI 10.1002/dvdy.20792 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 046NB UT WOS:000237817200009 PM 16586445 ER PT J AU Inada, A Nienaber, C Fonseca, S Bonner-Weir, S AF Inada, A Nienaber, C Fonseca, S Bonner-Weir, S TI Timing and expression pattern of carbonic anhydrase II in pancreas SO DEVELOPMENTAL DYNAMICS LA English DT Article DE carbonic anhydrase II; duct; pancreas ID BETA-CELLS; DUCT-CELL; GENE-EXPRESSION; TRANSGENIC MICE; PROMOTER; PROLIFERATION; DIFFERENTIATION; REGENERATION; SEQUENCES AB In the search for genetic markers for assessing the role of duct cells in pancreas growth, we examined whether carbonic anhydrase II (CAII) has ductal cell specificity. We determined the distribution and timing of CAII expression in mouse pancreas from embryonic stage to adult. The pancreatic ducts only start expressing CAII at embryonic day (E) 18.5, with increases after birth. Around E15.5, glucagon-positive cells, but not insulin-positive cells, also express CAII, with further increases by adult. CAII expression was restricted to cells within ductal structures and glucagon-positive cells with no colocalization with any insulin-positive cells at any time. In the human pancreas, CAII expression is restricted to the ducts. Furthermore, the activity of a 1.6-kb fragment of the human promoter with Luciferase assays was moderately strong compared with the cytomegalovirus promoter in human pancreatic duct cell line (PANG 1). Thus, we believe that the CAII gene could serve as a useful pancreatic duct cell marker. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplanta & Cell Biol, Boston, MA 02215 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplanta & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 FU NIDDK NIH HHS [DK 36863, DK 44523] NR 32 TC 17 Z9 18 U1 3 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 2006 VL 235 IS 6 BP 1571 EP 1577 DI 10.1002/dvdy.20754 PG 7 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 046NB UT WOS:000237817200012 PM 16586439 ER PT J AU Komers, R Schutzer, WE Reed, JF Lindsley, JN Oyama, TT Buck, DC Mader, SL Anderson, S AF Komers, R Schutzer, WE Reed, JF Lindsley, JN Oyama, TT Buck, DC Mader, SL Anderson, S TI Altered endothelial nitric oxide synthase targeting and conformation and caveolin-1 expression in the diabetic kidney SO DIABETES LA English DT Article ID RENAL HEMODYNAMIC-CHANGES; GLOMERULAR HYPERFILTRATION; CARDIAC MYOCYTES; OXIDATIVE STRESS; ENOS ACTIVATION; CELLS; RATS; DYSFUNCTION; NEPHROPATHY; TETRAHYDROBIOPTERIN AB Experimental diabetes is associated with complex changes in renal nitric oxide (NO) bioavailability. We explored the effect of diabetes on renal cortical protein expression of endothelial NO synthase (eNOS) with respect to several determinants of its enzymatic function, such as eNOS expression, membrane localization, phosphorylation, and dimerization, in moderately hyperglycemic streptozotocin-induced diabetic rats compared with nondiabetic control rats and diabetic rats with intensive insulin treatment to achieve near-normal metabolic control. We studied renal cortical expression and localization of caveolin-1 (CAV-1), an endogenons modulator of eNOS function. Despite similar whole-cell eNOS expression in all groups, eNOS monomer and dimer in membrane fractions were reduced in moderately hyperglycemic diabetic rats compared with control rats; the opposite trend was apparent in the cytosol. Stimulatory phosphorylation of eNOS (Ser1177) was also reduced in moderately hyperglycemic diabetic rats. eNOS colocalized and interacted with CAV-1 in endothelial cells throughout the renal vascular tree both in control and moderately hyperglycemic diabetic rats. However, the abundance of membrane-localized CAV-1 was decreased in diabetic kidneys. Intensive insulin treatment reversed the effects of diabetes on each of these parameters. In summary, we observed diabetes-mediated alterations in eNOS and CAV-1 expression that are consistent with the view of decreased bioavailability of renal eNOS-derived NO. C1 Oregon Hlth Sci Univ, Div Nephrol & Hypertens PP262, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Inst Clin & Expt Med, Diabet Ctr, Prague, Czech Republic. Portland VA Med Ctr, Res Serv, Portland, OR USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 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-63231] NR 48 TC 48 Z9 50 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2006 VL 55 IS 6 BP 1651 EP 1659 DI 10.2337/db05-1595 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YI UT WOS:000238053400013 PM 16731827 ER PT J AU Boyko, EJ Ahroni, JH Cohen, V Nelson, KM Heagerty, PJ AF Boyko, EJ Ahroni, JH Cohen, V Nelson, KM Heagerty, PJ TI Prediction of diabetic foot ulcer occurrence using commonly available clinical information - The Seattle diabetic foot study SO DIABETES CARE LA English DT Article ID LOWER-EXTREMITY AMPUTATION; PRIMARY HEALTH-CARE; AUTONOMIC NEUROPATHY; RISK-FACTORS; MANAGEMENT; DIAGNOSIS; COMMUNITY; DISEASE AB OBJECTIVE- The ability of readily available clinical information to predict the occurrence of diabetic foot ulcer has not been extensively studied. We conducted a prospective study of the individual and combined effects of commonly available clinical information in the prediction of diabetic foot ulcer occurrence. RESEARCH DESIGN AND METHODS- We followed 1,285 diabetic veterans without foot ulcer for this outcome with annual clinical evaluations and quarterly mailed questionnaires to identify foot problems. At baseline we assessed age; race; weight; current smoking; l ation diabetes duration and treatment; HbA(1c) (AlC); visual acuity; history of laser photocoagu and amputation; foot shape; claudication; foot insensitivity to the 10-g monofilament, foot callus, pedal edema; hallux limitus, Linea pedis and onychomycosis. Cox proportional hazards modeling was used with backwards stepwise elimination to develop a prediction model for the first foot ulcer occurrence after the baseline examination. RESULTS - At baseline, subjects were 62.4 years of age on average and 981/o male. Mean follow-up duration was 3.38 years, during which time 216 foot ulcers occurred, for an incidence of 5.0/100 person-years. Significant predictors (P <= 0.05) of foot ulcer in the final model (hazard ratio, 95% CI) included A1C (1.10, 1.06-1.15), impaired vision (1.48, 1.00-2.18), prior foot ulcer (2.18, 1.50-2.95) prior amputation (2.57, 1.60-4.12), monofilament insensivity) (2.03, 1.50-2.76), tinea pedis (0. 73, 0.54-0.98), and onychomycosis (1.58, 1.16-2.16). Area under the receiver operating characteristic curve was 0.81 at 1 year and 0.76 at 5 years. CONCLUSIONS - Readily available clinical information has substantial predictive power for the development of diabetic foot ulcer and may help in accurately targeting persons at high risk of this outcome for preventive interventions. C1 VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), VA Puget Sound S152E, 1660 S Columbian Way, Seattle, WA 98108 USA. EM eboyko@u.washington.edu NR 21 TC 111 Z9 117 U1 0 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2006 VL 29 IS 6 BP 1202 EP 1207 DI 10.2337/dc05-2031 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YG UT WOS:000238053200002 PM 16731996 ER PT J AU Lavery, LA Armstrong, DG Wunderlich, RP Mohler, MJ Wendel, CS Lipsky, BA AF Lavery, LA Armstrong, DG Wunderlich, RP Mohler, MJ Wendel, CS Lipsky, BA TI Risk factors for foot infections in individuals with diabetes SO DIABETES CARE LA English DT Article ID CLASSIFICATION-SYSTEM; MEXICAN-AMERICANS; PUNCTURE WOUNDS; ULCERATION; ULCERS; OSTEOMYELITIS; AMPUTATION; DISEASE; MULTICENTER; PRESSURES AB OBJECTIVE - To prospectively determine risk factors for foot infection in a cohort of people with diabetes. RESEARCH DESIGN AND METHODS - We evaluated then followed 1,666 consecutive diabetic patients enrolled in a managed care-based outpatient clinic in a 2-year longitudinal outcomes study. At enrollment, patients underwent a standardized general medical examination and detailed foot assessment and were educated about proper foot care. They were then rescreened at scheduled intervals and also seen promptly if they developed any foot problem. RESULTS - During the evaluation period, 151 (9.1%) patients developed 199 foot infections, all but one involving a wound or penetrating injury. Most patients had infections involving only the soft tissue, but 19.9% had bone culture-proven osteomyelitis. For those who developed a foot infection, compared with those who did not, the risk of hospitalization was 55.7 times greater (95% CI 30.3-102.2; P < 0.001) and the risk of amputation was 154.5 times greater (58.5-468.5; P < 0.001). Foot wounds preceded all but one infection. Significant (P < 0.05) independent risk factors for foot infection from a multivariate analysis included wounds that penetrated to bone (odds ratio 6.7), wounds with a duration > 30 days (4.7), recurrent wounds (2.4), wounds with a traumatic etiology (2.4), and presence of peripheral vascular disease (1.9). CONCLUSIONS - Foot infections occur relatively frequently in individuals with diabetes, almost always follow trauma, and dramatically increase the risk of hospitalization and amputation. Efforts to prevent infections should be targeted at people with traumatic foot wounds, especially those that are chronic, deep, recurrent, or associated with peripheral vascular disease. C1 Texas A&M Univ, Coll Med, Dept Surg, Scott & White Hosp,Hlth Sci Ctr, Temple, TX 76508 USA. Rosalind Franklin Univ Med & Sci, Dr William M Scholl Coll Podiatr Med, Chicago, IL USA. Manchester Royal Infirm, Dept Med, Manchester M13 9WL, Lancs, England. Diabetex, San Antonio, TX USA. So Arizona Vet Affairs Med Ctr, Res Serv, Tucson, AZ USA. Univ Arizona, Coll Publ Hlth, Epidemiol & Biostat Div, Tucson, AZ USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Lavery, LA (reprint author), Scott & White Hosp, Dept Surg, 703 Highland Spring Ln, Georgetown, TX 78628 USA. EM llavery@swmail.sw.org OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 54 TC 199 Z9 215 U1 1 U2 17 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2006 VL 29 IS 6 BP 1288 EP 1293 DI 10.2337/dc05-2425 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YG UT WOS:000238053200016 PM 16732010 ER PT J AU Utzschneider, KM Trence, DL AF Utzschneider, KM Trence, DL TI Effectiveness of gastric bypass surgery in a patient with familial partial lipodystrophy SO DIABETES CARE LA English DT Article ID SEVERELY OBESE SUBJECTS; OF-THE-LITERATURE; INSULIN SENSITIVITY; CLINICAL-FEATURES; WEIGHT-LOSS; RESISTANCE; DERANGEMENTS; ADIPONECTIN C1 VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. RP Utzschneider, KM (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM kutzschn@u.washington.edu FU NCRR NIH HHS [M01 RR 00037]; NIDDK NIH HHS [T32 DK 07247] NR 15 TC 9 Z9 9 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2006 VL 29 IS 6 BP 1380 EP 1382 DI 10.2337/dc06-0130 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YG UT WOS:000238053200031 PM 16732025 ER PT J AU Grant, RW McCarthy, EP Singer, DE Meigs, JB AF Grant, RW McCarthy, EP Singer, DE Meigs, JB TI Frequent outpatient contact and decreasing medication affordability in patients with diabetes from 1997 to 2004 SO DIABETES CARE LA English DT Article ID UNITED-STATES; OBESITY; COST; CARE; PREVALENCE; BURDEN C1 Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Gen Med Unit, Boston, MA 02215 USA. Harvard Med Sch, Boston, MA USA. RP Grant, RW (reprint author), 50-9 Staniford St, Boston, MA 02114 USA. EM rgrant@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIDDK NIH HHS [K23 DK067452-02, K23 DK067452, DK 067452] NR 16 TC 9 Z9 9 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2006 VL 29 IS 6 BP 1386 EP 1388 DI 10.2337/dc06-0196 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YG UT WOS:000238053200033 PM 16732027 ER PT J AU Hood, KK Huestis, S Maher, A Butler, D Volkening, L Laffel, LMB AF Hood, KK Huestis, S Maher, A Butler, D Volkening, L Laffel, LMB TI Depressive symptoms in children and adolescents with type 1 diabetes - Association with diabetes-specific characteristics SO DIABETES CARE LA English DT Article ID FOLLOW-UP; FAMILY; ADJUSTMENT; MELLITUS; ONSET; AGE C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat & Adolescent Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Behav Res & Mental Hlth Sect, Boston, MA 02215 USA. RP Laffel, LMB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat & Adolescent Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIDDK NIH HHS [DK 46887, K23 DK 073340] NR 21 TC 131 Z9 133 U1 6 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2006 VL 29 IS 6 BP 1389 EP 1391 DI 10.2337/dc06-0087 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YG UT WOS:000238053200034 PM 16732028 ER PT J AU Goodwin, G Volkening, LK Laffel, LMB AF Goodwin, G Volkening, LK Laffel, LMB TI Younger age at onset of type 1 diabetes in concordant sibling pairs is associated with increased risk for autoimmune thyroid disease SO DIABETES CARE LA English DT Article ID CELIAC-DISEASE; DEGREE RELATIVES; CHILDREN; ADOLESCENTS; MELLITUS; AUTOANTIBODIES C1 Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIDDK NIH HHS [K12 DK 63696-01] NR 11 TC 6 Z9 7 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2006 VL 29 IS 6 BP 1397 EP 1398 DI 10.2337/dc06-0098 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YG UT WOS:000238053200037 PM 16732031 ER PT J AU Huebschmann, AG Regensteiner, JG Vlassara, H Reusch, JEB AF Huebschmann, AG Regensteiner, JG Vlassara, H Reusch, JEB TI Diabetes and advanced glycoxidation end products SO DIABETES CARE LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; ADVANCED GLYCATION ENDPRODUCTS; ALDOSE REDUCTASE INHIBITOR; ALPHA-LIPOIC ACID; NF-KAPPA-B; CULTURED ENDOTHELIAL-CELLS; MAILLARD REACTION-PRODUCTS; CONTROLLED-TRIAL ALADIN; RENAL-FAILURE PATIENTS; CROSS-LINK BREAKER C1 Univ Colorado, Dept Med, Div Cardiol, Denver, CO USA. Univ Colorado, Div Gen Internal Med, Denver, CO USA. Hlth Sci Ctr, Denver, CO USA. Mt Sinai Sch Med, Div Expt Diabet & Aging, Dept Geriatr, New York, NY USA. Univ Colorado, Dept Med, Div Endocrinol, Denver, CO USA. Denver VA Med Ctr, Denver, CO USA. RP Huebschmann, AG (reprint author), Univ Colorado, POB 6510,Mailstop F-729, Aurora, CO 80045 USA. EM amy.huebschmann@uchsc.edu NR 200 TC 131 Z9 147 U1 3 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2006 VL 29 IS 6 BP 1420 EP 1432 DI 10.2337/dc05-2096 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YG UT WOS:000238053200045 PM 16732039 ER PT J AU Kulke, MH Wu, BY Ryan, DP Enzinger, PC Zhu, AX Clark, JW Earle, CC Michelini, A Fuchs, CS AF Kulke, Matthew H. Wu, Bingyan Ryan, David P. Enzinger, Peter C. Zhu, Andrew X. Clark, Jeffrey W. Earle, Craig C. Michelini, Ann Fuchs, Charles S. TI A phase II trial of irinotecan and cisplatin in patients with metastatic neuroendocrine tumors SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE pancreatic islet cell tumors; carcinoid tumors; neuroendocrine tumors; cisplatin; irinotecan ID ISLET-CELL CARCINOMA; PLUS FLUOROURACIL; COLORECTAL-CANCER; ONCOLOGY-GROUP; STREPTOZOCIN; DOXORUBICIN; ETOPOSIDE; EFFICACY; FAILURE; LUNG AB The role of systemic chemotherapy in the treatment of patients with metastatic neuroendocrine tumors is controversial. While combination regimens containing cisplatin and etoposide have activity against more aggressive neuroendocrine tumor variants, such regimens appear to have little efficacy in patients with well-differentiated neuroendocrine tumor subtypes. The combination of irinotecan and cisplatin is active both against small cell lung cancer and in upper gastrointestinal malignancies but has not been prospectively evaluated in patients with metastatic neuroendocrine tumors. We therefore assessed the efficacy of an irinotecan/cisplatin combination in patients with this disease. Eighteen patients with metastatic neuroendocrine tumors (excluding small cell carcinoma) were treated with irinotecan, 65 mg/m(2), and cisplatin, 30 mg/m(2) stop, administered weekly for 2 of every 3 weeks. Patients were followed for evidence of toxicity, response, and survival. The toxicities associated with this regimen were mild and included myelosuppression, nausea, and diarrhea. Only one radiologic response was observed among four patients with poorly differentiated neuroendocrine tumors. No radiologic responses were observed in 14 patients with well-differentiated tumors. The median overall survival duration of patients treated with this regimen was 11.4 months. We conclude that while the combination of irinotecan and cisplatin may have activity in aggressive neuroendocrine tumor subtypes, this combination is inactive in patients with well-differentiated neuroendocrine tumors. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Dana Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Biney St, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu FU NCI NIH HHS [K23 CA 093401]; NHLBI NIH HHS [K30 HL04095] NR 22 TC 42 Z9 43 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2006 VL 51 IS 6 BP 1033 EP 1038 DI 10.1007/s10620-006-8001-3 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 067IR UT WOS:000239295700001 PM 16865563 ER PT J AU Saunders, GH Forsline, A AF Saunders, GH Forsline, A TI The performance-perceptual test (PPT) and its relationship to aided reported handicap and hearing aid satisfaction SO EAR AND HEARING LA English DT Article ID DECISION-MAKING; INVENTORY; BENEFIT; LIFE; AGE AB Objective: Results of objective clinical tests (e.g., measures of speech understanding in noise) often conflict with subjective reports of hearing aid benefit and satisfaction. The Performance-Perceptual Test (PPT) is an outcome measure in which objective and subjective evaluations are made by using the same test materials, testing format, and unit of measurement (signal-to-noise ratio, S/N), permitting a direct comparison between measured and perceived ability to hear. Two variables are measured: a Performance Speech Reception Threshold in Noise (SRTN) for 50% correct performance and a Perceptual SRTN, which is the S/N at which listeners perceive that they can understand the speech material. A third variable is computed: the Performance-Perceptual Discrepancy (PPDIS); it is the difference between the Performance and Perceptual SRTNs and measures the extent to which listeners "misjudge" their hearing ability. Saunders et al. in 2004 examined the relation between PPT scores and unaided hearing handicap. In this publication, the relations between the PPT, residual aided handicap, and hearing aid satisfaction are described. Design: Ninety-four individuals between the ages of 47 and 86 yr participated. All had symmetrical sensorineural hearing loss and had worn binaural hearing aids for at least 6 wk before participating. All subjects underwent routine audiological examination and completed the PPT, the Hearing Handicap Inventory for the Elderly/Adults (HHIE/A), and the Satisfaction for Amplification in Daily Life questionnaire. Sixty-five subjects attended one research visit for participation in this study, and 29 attended a second visit to complete the PPT a second time. Results: Performance and Perceptual SRTN and PPDIS scores were normally distributed and showed excellent test-retest reliability. Aided SRTNs were significantly better than unaided SRTNs; aided and unaided PPDIS values did not differ. Stepwise multiple linear regression showed that the PPDIS, the Performance SRTN, and age were significant predictors of scores on the HHIE/A such that greater reported handicap is associated with underestimating hearing ability, poorer aided ability to understand speech in noise, and being younger. Scores on the Satisfaction with Amplification in Daily Life were not well explained by the PPT, age, or audiometric thresholds. When individuals were grouped by their HHIE/A scores, it was seen that individuals who report more handicap than expected based on their audiometric thresholds, have a more negative PPDIS, i.e., underestimate their hearing ability, relative to individuals who report expected handicap, who in turn have a more negative PPDIS than individuals who report less handicap than expected. No such patterns were apparent for the Performance SRTN. Conclusions: The study showed the PPT to be a reliable outcome measure that can provide more information than a performance measure and/or a questionnaire measure alone, in that the PPDIS can provide the clinician with an explanation for discrepant objective and subjective reports of hearing difficulties. The finding that self-reported handicap is affected independently by both actual ability to hear and the (mis)perception of ability to hear underscores the difficulty clinicians encounter when trying to interpret outcomes questionnaires. We suggest that this variable should be measured and taken into account when interpreting questionnaires and counseling patients. C1 Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97207 USA. RP Saunders, GH (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. EM gabrielle.saunders@med.va.gov NR 30 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD JUN PY 2006 VL 27 IS 3 BP 229 EP 242 DI 10.1097/01.aud.0000215976.64444.e6 PG 14 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 041GB UT WOS:000237441200003 PM 16672792 ER PT J AU Lynch, TJ AF Lynch, Thomas J., Jr. TI Molecular staging of NSCLC: 2006 SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2006 VL 4 IS 6 MA S55 BP 24 EP 25 DI 10.1016/j.ejcsup.2006.04.057 PG 2 WC Oncology SC Oncology GA 062UF UT WOS:000238969500057 ER PT J AU Nakamura, E Kaelin, WG AF Nakamura, Eijiro Kaelin, William G., Jr. TI Recent insights into the molecular pathogenesis of pheochromocytoma and paraganglioma SO ENDOCRINE PATHOLOGY LA English DT Review DE pheochromocytoma; paragangliomas; VHL; RET; NF1; SDH ID VON-HIPPEL-LINDAU; ENDOCRINE NEOPLASIA TYPE-2; HYPOXIA-INDUCIBLE-FACTOR; TUMOR-SUPPRESSOR PROTEIN; PROGRAMMED CELL-DEATH; GERM-LINE MUTATIONS; COMPLEX-II GENE; KINASE-C-ZETA; RET PROTOONCOGENE; SPORADIC PHEOCHROMOCYTOMAS AB Pheochromocytomas and paragangliomas are rare tumors derived from chromaffin cells. These tumors can arise in the context of hereditary cancer syndromes such as von Hippel-Lindau disease, multiple endocrine neoplasia type,2, and neurofibromatosis 1. Recent studies indicate that germ line mutations of genes encoding specific succinate dehydrogenase (SDH) subunits also predispose individuals to pheochromocytomas and paragangliomas. This review focuses on the genetics of these tumors and suggests a possible link between familial pheochromocytomas/paraganglioma. genes and control of neuronal apoptosis during embryological development. C1 Kyoto Univ, Grad Sch Med, Dept Urol, Kyoto, Japan. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Nakamura, E (reprint author), Kyoto Univ, Grad Sch Med, Dept Urol, Kyoto, Japan. NR 63 TC 21 Z9 22 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1046-3976 J9 ENDOCR PATHOL JI Endocr. Pathol. PD SUM PY 2006 VL 17 IS 2 BP 97 EP 106 DI 10.1385/EP:17:2:97 PG 10 WC Endocrinology & Metabolism; Pathology SC Endocrinology & Metabolism; Pathology GA 109ZT UT WOS:000242348800001 PM 17159241 ER PT J AU Mundinger, TO Cummings, DE Taborsky, GJ AF Mundinger, Thomas O. Cummings, David E. Taborsky, Gerald J., Jr. TI Direct stimulation of ghrelin secretion by sympathetic nerves SO ENDOCRINOLOGY LA English DT Article ID PLASMA GHRELIN; NERVOUS-SYSTEM; NEUROPEPTIDE-Y; ADIPOSE-TISSUE; COLD-EXPOSURE; ACTIVE FORM; FOOD-INTAKE; RATS; RELEASE; HUMANS AB The hormone ghrelin is secreted mainly from the gut, rises in peripheral plasma before meals, and is implicated in stimulating hunger, initiating meals, and developing obesity. We hypothesize that activation of the sympathetic nervous system contributes to preprandial ghrelin surges. The present studies in isoflurane-anesthetized Wistar rats were designed to determine whether sympathetic nerves and neurohormones are capable of stimulating ghrelin secretion. We activated gut sympathetic nerves by two methods: electrical sympathetic nerve stimulation (SNS) and chemical sympathetic nerve activation with iv tyramine (TYR) administration. Portal venous blood was sampled before and during a 10-min sympathetic stimulation. Successful activation of gut sympathetic nerves was verified by increments in portal venous norepinephrine. SNS increased portal ghrelin by 206 +/- 50%. In contrast, simply isolating gut sympathetic nerves without applying current had a minimal effect on ghrelin levels. TYR also increased portal ghrelin [change (Delta), + 52 +/- 11%], whereas saline infusion had little effect. We next determined whether the neural stimulation of ghrelin secretion was mediated indirectly via the suppression of insulin secretion during SNS and TYR. Streptozotocin-induced diabetes prevented a fall in insulin during TYR, yet the portal ghrelin response (Delta = + 47 +/- 18%) was similar to that in nondiabetic rats. Lastly, to test for humoral stimulation of ghrelin, we infused the sympathetic neurohormone, epinephrine, to achieve levels found during severe stress. Epinephrine failed to stimulate ghrelin secretion (Delta = + 4 +/- 35%). We conclude that the neural, but not the neurohumoral, branch of the sympathetic nervous system can directly stimulate ghrelin secretion. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Mundinger, TO (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM mundin@u.washington.edu FU NIDDK NIH HHS [DK-17047, DK-12829, DK-50154, DK-61516, DK-68384] NR 71 TC 79 Z9 82 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2006 VL 147 IS 6 SU S BP 2893 EP 2901 DI 10.1210/en.2005-1182 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 043SF UT WOS:000237621200044 PM 16527847 ER PT J AU Eto, K Kaur, V Thomas, MK AF Eto, Kazuhiro Kaur, Varinderpal Thomas, Melissa K. TI Regulation of insulin gene transcription by the immediate-early growth response gene Egr-1 SO ENDOCRINOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; DOMINANT-NEGATIVE INHIBITOR; LOOP-HELIX PROTEINS; ISLET CELLS; FACTOR-I; MAMMALIAN-CELLS; NGFI-A; ENDOTHELIAL-CELLS; TRANSGENIC MICE; HOMEOBOX FACTOR AB Changes in extracellular glucose levels regulate the expression of the immediate-early response gene and zinc finger transcription factor early growth response-1 (Egr-1) in insulin-producing pancreatic beta-cells, but key target genes of Egr-1 in the endocrine pancreas have not been identified. We found that overexpression of Egr-1 in clonal (INS-1) beta-cells increased transcriptional activation of the rat insulin I promoter. In contrast, reductions in Egr-1 expression levels or function with the introduction of either small interfering RNA targeted to Egr-1 (siEgr-1) or a dominant-negative form of Egr-1 decreased insulin promoter activation, and siEgr-1 suppressed insulin gene expression. Egr-1 did not directly interact with insulin promoter sequences, and mutagenesis of a potential G box recognition sequence for Egr-1 did not impair the Egr-1 responsiveness of the insulin promoter, suggesting that regulation of insulin gene expression by Egr-1 is probably mediated through additional transcription factors. Overexpression of Egr-1 increased, and reduction of Egr-1 expression decreased, transcriptional activation of the glucose-responsive FarFlat minienhancer within the rat insulin I promoter despite the absence of demonstrable Egr-1-binding activity to FarFlat sequences. Notably, augmenting Egr-1 expression levels in insulin-producing cells increased the mRNA and protein expression levels of pancreas duodenum homeobox-1 (PDX-1), a major transcriptional regulator of glucose-responsive activation of the insulin gene. Increasing Egr-1 expression levels enhanced PDX-1 binding to insulin promoter sequences, whereas mutagenesis of PDX-1-binding sites reduced the capacity of Egr-1 to activate the insulin promoter. We propose that changes in Egr-1 expression levels in response to extracellular signals, including glucose, can regulate PDX-1 expression and insulin production in pancreatic beta-cells. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Thomas, MK (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Thier 340,50 Blossom St, Boston, MA 02114 USA. EM mthomas1@partners.org FU NIDDK NIH HHS [P30DK57521] NR 74 TC 22 Z9 22 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2006 VL 147 IS 6 SU S BP 2923 EP 2935 DI 10.1210/en.2005-1336 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 043SF UT WOS:000237621200048 PM 16543365 ER PT J AU Rukstalis, JM Ubeda, M Johnson, MV Habener, JF AF Rukstalis, J. Michael Ubeda, Mariano Johnson, Megan V. Habener, Joel F. TI Transcription factor snail modulates hormone expression in established endocrine pancreatic cell lines SO ENDOCRINOLOGY LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; INSULIN GENE-EXPRESSION; DOWN-REGULATION; REGENERATION; BETA; DEDIFFERENTIATION; PROLIFERATION; TUMORIGENESIS; REPRESSORS; INDUCTION AB The development of differentiated cells from undifferentiated progenitor cells is one of the central tenets of developmental biology. However, under conditions of tissue morphogenesis, regeneration, and cancer, this process of development is reversed and fully differentiated cells transition to an undifferentiated phenotype. Here we present evidence that the zinc-finger transcription factor Snail modulates this transition in differentiated pancreatic endocrine cell lines. During passage and growth of these cell lines, Snail expression is induced in a subset of cells within the culture, concomitant with a decrease in insulin and/or glucagon expression. As the cells cluster and exit the cell division cycle, nuclear levels of Snail are reduced and hormone expression is resumed. Snail represses proinsulin and proglucagon gene transcription, and reduction of Snail levels by small interfering RNA treatment increases proinsulin gene expression. We propose that Snail modulates the dynamic balance between differentiated and dedifferentiated cells allowing their migration and proliferation. These findings may be relevant to providing approaches for the enhancement of beta-cell growth in individuals with diabetes mellitus. C1 Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, 55 Fruit St,Their 320, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [DK61251, T32-DK07028-29, DK55365] NR 31 TC 6 Z9 6 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2006 VL 147 IS 6 SU S BP 2997 EP 3006 DI 10.1210/en.2005-1396 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 043SF UT WOS:000237621200055 PM 16556769 ER PT J AU Arufe, MC Lu, M Kubo, A Keller, G Davies, TF Lin, RY AF Arufe, Maria C. Lu, Min Kubo, Atsushi Keller, Gordon Davies, Terry F. Lin, Reigh-Yi TI Directed differentiation of mouse embryonic stem cells into thyroid follicular cells SO ENDOCRINOLOGY LA English DT Article ID IN-VITRO DIFFERENTIATION; SYSTEM CHARACTERIZATION; TRANSCRIPTION FACTORS; THYROTROPIN RECEPTOR; PLURIPOTENTIAL CELLS; EPITHELIAL-CELLS; GROWTH; FRTL-5; THYROGLOBULIN; INVITRO AB Elucidating the molecular mechanisms leading to the induction and specification of thyroid follicular cells is important for our understanding of thyroid development. To characterize the key events in this process, we previously established an experimental embryonic stem (ES) cell model system, which shows that wild-type mouse CCE ES cells can give rise to thyrocyte-like cells in vitro. We extend our analysis in this report by using a genetically manipulated ES cell line in which green fluorescent protein (GFP) cDNA is targeted to the TSH receptor (TSHR) gene, linking GFP expression to the transcription of the endogenous TSHR gene. The appearance of GFP-positive cells was dependent on the formation of embryoid bodies from undifferentiated ES cells and was greatly enhanced by TSH treatment during the first 2-4 d of differentiation. With the support of Matrigel, highly enriched ES cell-derived GFP-positive cells formed thyroid follicle-like clusters in a serum-free medium supplemented with TSH. Importantly, these clusters display the characteristics of thyroid follicular cells. Immunofluorescent studies confirmed the colocalization of TSHRwith the Na+/I- symporter in the clusters and indicated that Na+/I- symporter was expressed exclusively in the plasma membrane. In addition, I- uptake activity was observed in these cells. Our results indicate that ES cells can be induced to differentiate into thyroid follicular cells, providing a powerful tool to study embryonic thyroid development and function. C1 Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, Dept Med, Beijing 100029, Peoples R China. Mt Sinai Sch Med, Dept Gene & Cell Med, Beijing 100029, Peoples R China. Nara Med Univ, Dept Publ Hlth, Nara 6348521, Japan. James J Peters Vet Adm Med Ctr, Div Endocrinol & Metab, Bronx, NY 10468 USA. RP Lin, RY (reprint author), Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, Dept Med, Box 1055,1 Gustave L Levy Pl, Beijing 100029, Peoples R China. EM reigh-yi.lin@mssm.edu RI arufe gonda, maria/N-3189-2014 OI arufe gonda, maria/0000-0003-3725-0743 FU NIDDK NIH HHS [R01-DK-068057-01A1, R01 DK068057] NR 41 TC 33 Z9 43 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 2006 VL 147 IS 6 SU S BP 3007 EP 3015 DI 10.1210/en.2005-1239 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 043SF UT WOS:000237621200056 PM 16497809 ER PT J AU Maiss, J Dumser, C Zopf, Y Naegel, A Krauss, N Hochberger, J Matthes, K Hahn, EG Schwab, D AF Maiss, J. Dumser, C. Zopf, Y. Naegel, A. Krauss, N. Hochberger, J. Matthes, K. Hahn, E. G. Schwab, D. TI "Hemodynamic efficacy" of two endoscopic clip devices used in the treatment of bleeding vessels, tested in an experimental setting using the compact Erlangen Active Simulator for Interventional Endoscopy (compactEASIE) training model SO ENDOSCOPY LA English DT Article ID RANDOMIZED-TRIAL; PEPTIC-ULCER; INJECTION; HEMOSTASIS; HEMOCLIP; THERAPY; EPINEPHRINE; HEMORRHAGE; ENDOCLIPS; ARTERIES AB Background and Study Aims: Hemoclip therapy is a well-established procedure in the treatment of gastrointestinal bleeding. Although new products are provided periodically by the industry, comparative investigations are lacking. We compared two different hemoclip devices in an experimental setting, assessing them using objective hemostatic parameters. Materials and Methods: We compared two disposable clip devices (Olympus HX-20OL-135 (n = 40) vs. Wilson-Cook Tri-Clip (n = 40)) in an experimental setting using the compact Erlangen Active Simulator for Interventional Endoscopy (compactEASIE) training model equipped with an upper gastrointestinal-organ package for bleeding simulation. This was a randomized, prospective, controlled trial. Four investigators with different levels of endoscopic experience applied ten hemoclip devices of each type to the spurting vessels, the clips allocated using a randomized list for each investigator. The efficacy of hemostasis was determined by continuous measurement of the pressure within the afferent vessel before and after clip application and calculation of the relative reduction of vessel diameter by the clip device. The system pressure was recorded over the period from 1 minute before to 1 minute after clip application. A secondary end point was a subjective assessment of the whole clip application procedure by the endoscopist and the assisting nurse, using a visual analog scale (0-100, with 100 representing the best experience). Results: A total of 39/40 clips of each type were applied successfully. Both clip devices led to a significant increase in system pressure, representing significant relative reduction of vessel diameter (Olympus 5.4 +/- 7.5%, p < 0.001; Cook 4.9 +/- 8.0%, p < 0.001). Overall, there was no significant difference between the two devices (P = 0.756). However, the investigator with the least experience in endoscopy (< 100 procedures) produced significantly inferior results compared with the other three investigators, who had performed between 2000 and 6000 procedures each (P < 0.05). We found no evidence of a learning curve from the intra-observer results. The devices received good, but not significantly different, overall ratings by the endoscopists (Olympus 69 +/- 24 vs. Wilson-Cook 65 +/- 16) and by the assisting nurses (Olympus 77 +/- 9 vs. Wilson-Cook 70 +/- 22). Conclusions: Using an established cadaveric training model, no significant difference was found between the two types of hemoclip devices with respect to their "hemostatic efficacy". However, the experience of the endoscopist appears to play a major role in successful clip application. The use of a feedback mechanism in emergency endoscopy training, using continuous intravessel pressure monitoring, may substantially enhance the efficacy of training, resulting in a similar improvement in clinical results. C1 Univ Erlangen Nurnberg, Dept Med 1, D-91054 Erlangen, Germany. St Bernward Hosp, Dept Med 3, Hildesheim, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Martha Maria Hosp, Dept Med 2, Nurnberg, Germany. RP Maiss, J (reprint author), Univ Erlangen Nurnberg, Dept Med 1, Ulmenweg 18, D-91054 Erlangen, Germany. EM juergen.maiss@med1.imed.uni-erlangen.de NR 17 TC 25 Z9 25 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD JUN PY 2006 VL 38 IS 6 BP 575 EP 580 DI 10.1055/s-2006-925000 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 061YQ UT WOS:000238911000005 PM 16802269 ER PT J AU Brugge, WR AF Brugge, W. R. TI Cystic pancreatic lesions: Can we diagnose them accurately what to look for? FNA marker molecular analysis resection, surveillance, or endoscopic treatment? SO ENDOSCOPY LA English DT Article; Proceedings Paper CT 15th International Symposium on Endoscopic Ultrasound CY JUN 28-30, 2006 CL Amsterdam, NETHERLANDS ID PAPILLARY MUCINOUS TUMORS; FINE-NEEDLE-ASPIRATION; HIPPEL-LINDAU-DISEASE; FLUID ANALYSIS; DIFFERENTIAL-DIAGNOSIS; NEUROENDOCRINE TUMORS; MICROCYSTIC ADENOMAS; SURGICAL-MANAGEMENT; SUPPRESSOR GENE; FOLLOW-UP C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Unit, Blake 452, Boston, MA 02114 USA. EM brugge.william@mgh.harvard.edu NR 69 TC 14 Z9 15 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD JUN PY 2006 VL 38 SU 1 BP S40 EP S47 DI 10.1055/s-2006-946650 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 063JK UT WOS:000239014300011 PM 16802222 ER PT J AU Karayiannis, NB Xiong, YH Tao, GZ Frost, JD Wise, MS Hrachovy, RA Mizrahi, EM AF Karayiannis, NB Xiong, YH Tao, GZ Frost, JD Wise, MS Hrachovy, RA Mizrahi, EM TI Automated detection of videotaped neonatal seizures of epileptic origin SO EPILEPSIA LA English DT Article DE motion segmentation; motion-strength signal; motion tracking; motion-trajectory signal; neonatal seizure; neural network; quantitative feature; video recording ID MOTOR-ACTIVITY SIGNALS; QUANTUM NEURAL-NETWORKS; QUANTIFYING MOTION; RECORDINGS; EEG; RISK; CONVULSIONS; EXTRACTION; NEWBORN; COUNTY AB Purpose: This study aimed at the development of a seizure-detection system by training neural networks with quantitative motion information extracted from short video segments of neonatal seizures of the myoclonic and focal clonic types and random infant movements. Methods: The motion of the infants' body parts was quantified by temporal motion-strength signals extracted from video segments by motion-segmentation methods based on optical flow computation. The area of each frame occupied by the infants' moving body parts was segmented by clustering the motion parameters obtained by fitting an affine model to the pixel velocities. The motion of the infants' body parts also was quantified by temporal motion-trajectory signals extracted from video recordings by robust motion trackers based on block-motion models. These motion trackers were developed to adjust autonomously to illumination and contrast changes that may occur during the video-frame sequence. Video segments were represented by quantitative features obtained by analyzing motion-strength and motion-trajectory signals in both the time and frequency domains. Seizure recognition was performed by conventional feed-forward neural networks, quantum neural networks, and cosine radial basis function neural networks, which were trained to detect neonatal seizures of the myoclonic and focal clonic types and to distinguish them from random infant movements. Results: The computational tools and procedures developed for automated seizure detection were evaluated on a set of 240 video segments of 54 patients exhibiting myoclonic seizures (80 segments), focal clonic seizures (80 segments), and random infant movements (80 segments). Regardless of the decision scheme used for interpreting the responses of the trained neural networks, all the neural network models exhibited sensitivity and specificity > 90%. For one of the decision schemes proposed for interpreting the responses of the trained neural networks, the majority of the trained neural-network models exhibited sensitivity > 90% and specificity > 95%. In particular, cosine radial basis function neural networks achieved the performance targets of this phase of the project (i.e., sensitivity > 95% and specificity > 95%). Conclusions: The best among the motion segmentation and tracking methods developed in this study produced quantitative features that constitute a reliable basis for detecting neonatal seizures. The performance targets of this phase of the project were achieved by combining the quantitative features obtained by analyzing motion-strength signals with those produced by analyzing motion-trajectory signals. The computational procedures and tools developed in this study to perform off-line analysis of short video segments will be used in the next phase of this project, which involves the integration of these procedures and tools into a system that can process and analyze long video recordings of infants monitored for seizures in real time. C1 Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Peter Kellaway Sect Neurophysiol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Karayiannis, NB (reprint author), Univ Houston, Dept Elect & Comp Engn, N308 Engn Bldg 1, Houston, TX 77204 USA. EM karayiannis@uh.edu FU NIBIB NIH HHS [1 R01 EB00183]; NINDS NIH HHS [N01-NS-2316] NR 40 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2006 VL 47 IS 6 BP 966 EP 980 DI 10.1111/j.1528-1167.2006.00571.x PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA 047IL UT WOS:000237872900006 PM 16822243 ER PT J AU Hicks, LS O'Malley, JA Landon, BE Lieu, TA Keegan, T Cook, NK McNeil, BJ Guadagnoli, E AF Hicks, L. S. O'Malley, J. A. Landon, B. E. Lieu, T. A. Keegan, T. Cook, N. K. McNeil, B. J. Guadagnoli, E. TI Determinants of quality of chronic disease management among community health centers in the United States SO ETHNICITY & DISEASE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Brigham & Womens Faulkner Hosp Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Brookline, MA 02146 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2006 VL 16 IS 3 BP S65 EP S65 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 067FO UT WOS:000239287400085 ER PT J AU Rieber, J Huber, A Erhard, I Mueller, S Schweyer, M Koenig, A Schiele, TM Theisen, K Siebert, U Schoenberg, SO Reiser, M Klauss, V AF Rieber, J Huber, A Erhard, I Mueller, S Schweyer, M Koenig, A Schiele, TM Theisen, K Siebert, U Schoenberg, SO Reiser, M Klauss, V TI Cardiac magnetic resonance perfusion imaging for the functional assessment of coronary artery disease: a comparison with coronary angiography and fractional flow reserve SO EUROPEAN HEART JOURNAL LA English DT Article DE CMRI; coronary artery disease; fractional flow reserve ID MYOCARDIAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; PRESSURE MEASUREMENTS; NUCLEAR CARDIOLOGY; FOLLOW-UP; MR; ANGIOPLASTY; STENOSIS; INDEX; DIAGNOSIS AB Aims Cardiac magnetic resonance perfusion imaging (CMRI) is a promising technique for non-invasive measurement of myocardial perfusion reserve. Fractional flow reserve (FFR) is an established invasive method for functional assessment of coronary artery disease (CAD). To prospectively assess the diagnostic value of CMRI for the detection of haemodynamically significant coronary lesions, compared with coronary angiography (CA) and FFR. Methods and results Forty-three patients with suspected or known CAD underwent CA, CMRI, and FFR measurement. First pass magnetic resonance perfusion examination was performed during hyperaemia (140 mu g/kg/min adenosine over 6 min) and at rest. One hundred and twenty-nine perfusion territories were assessed by semi-quantitative evaluation of signal intensity-time curves using the myocardial perfusion reserve index (MPRI) [upslope(stress(corrected))/upslope(rest(corrected))]. Perfusion territories were categorized as normal (coronary stenosis <= 50%), intermediate (stenosis > 50% and FFR > 0.75), or severe (stenosis > 50% and FFR <= 0.75 or total occlusion). MPRI values (+/- SD) were significantly different between the three categories [normal, 2.2 +/- 0.5 vs. intermediate, 1.8 +/- 0.5 (P = 0.005) and intermediate vs. severe, 1.2 +/- 0.3 (P < 0.001)]. An MPRI cut-off value of 1.5 (derived from receiver operating characteristics analysis) distinguished haemodynamically relevant (severe) from non-relevant (normal and intermediate) stenoses with a sensitivity of 88% (CI 74-100%) and a specificity of 90% (CI 84-96%). Conclusion In contrast to earlier studies that compared CMRI with morphological examination (CA) atone, the present study compared CMRI with CA plus a standard invasive functional assessment (FFR) and demonstrated that CMRI is able to distinguish haemodynamically relevant from non-relevant coronary lesions with a high sensitivity and specificity and may therefore contribute to clinical decision-making. C1 Univ Munich, Med Poliklin, Dept Cardiol, Div Internal Med, D-80336 Munich, Germany. Univ Munich, Inst Clin Radiol, D-80336 Munich, 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 Rieber, J (reprint author), Univ Munich, Med Poliklin, Dept Cardiol, Div Internal Med, Innenstadt Ziemssenstr 1, D-80336 Munich, Germany. EM johannes.rieber@med.uni-muenchen.de NR 42 TC 91 Z9 95 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUN PY 2006 VL 27 IS 12 BP 1465 EP 1471 DI 10.1093/eurheartj/ehl039 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 058QJ UT WOS:000238679400014 PM 16720685 ER PT J AU Ceron, J Tejedor, FJ Moya, F AF Ceron, J Tejedor, FJ Moya, F TI A primary cell culture of Drosophila postembryonic larval neuroblasts to study cell cycle and asymmetric division SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE cell division; cell culture; video recording; Drosophila neuroblasts; asymmetric division; prospero; numb; inscuteable; Miranda ID CENTRAL-NERVOUS-SYSTEM; PROLIFERATION PATTERN; PROTEIN LOCALIZATION; IN-VITRO; MELANOGASTER; DIFFERENTIATION; INTERFERENCE; EXPRESSION; PROSPERO; NEURONS AB Drosophila melanogaster is a key model system that has greatly contributed to the advance of developmental biology through its extensive and sophisticated genetics. Nevertheless, only a few in vitro approaches are available in Drosophila to complement genetic studies in order to better elucidate developmental mechanisms at the cellular and molecular level. Here we present a dissociated cell culture system generated from the optic lobes of Drosophila larval brain. This culture system makes it feasible to study the proliferative properties of Drosophila postembryonic Nbs by allowing BrdU pulse and chase assays, as well as detailed immunocytochemical analysis with molecular markers. These immunofluorescence experiments allowed us to conclude that localization of asymmetric cell division markers such as Inscuteable, Miranda, Prospero and Numb is cell autonomous. By time-lapse video recording we have observed interesting cellular features of postembryonic neurogenesis such us the polarized genesis of the neuroblast progeny, the extremely short ganglion mother cell (GMC) cell cycle, and the last division of a neuroblast lineage. The combination of this cell culture system and genetic tools of Drosophila will provide a powerful experimental model for the analysis of cell cycle and asymmetric cell division of neural progenitor cells. (c) 2006 Elsevier GmbH. All rights reserved. C1 CSIC, Inst Neurociencias, E-03550 Alicante, Spain. Univ Miguel Hernandez, E-03550 Alicante, Spain. RP Ceron, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 13th St,Bldg 149,7th Floor, Charlestown, MA 02129 USA. EM julian_ceron@hms.harvard.edu OI Tejedor, Francisco J/0000-0003-1942-2580 NR 36 TC 13 Z9 15 U1 0 U2 5 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD JUN PY 2006 VL 85 IS 6 BP 567 EP 575 DI 10.1016/j.ejcb.2006.02.006 PG 9 WC Cell Biology SC Cell Biology GA 056GK UT WOS:000238509700010 PM 16621131 ER PT J AU Sadri-Vakili, G Menon, AS Farrell, LA Keller-McGandy, CE Cantuti-Castelvetri, I Standaert, DG Augood, SJ Yohrling, GJ Cha, JHJ AF Sadri-Vakili, G. Menon, A. S. Farrell, L. A. Keller-McGandy, C. E. Cantuti-Castelvetri, I. Standaert, D. G. Augood, S. J. Yohrling, G. J. Cha, J-H. J. TI Huntingtin inclusions do not down-regulate specific genes in the R6/2 Huntington's disease mouse SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE Huntington's disease; in situ hybridization; inclusions; laser capture microdissection; striatum; transcription ID NEURONAL INTRANUCLEAR INCLUSIONS; MUTANT HUNTINGTIN; TRANSCRIPTIONAL DYSREGULATION; TRANSGENIC MICE; MESSENGER-RNA; REPEAT; BRAIN; MODEL; ABNORMALITIES; CHEMOTHERAPY AB Transcriptional dysregulation is a central pathogenic mechanism in Huntington's disease (HD); HID and transgenic mouse models of HID demonstrate down-regulation of specific genes at the level of mRNA expression. Furthermore, neuronal intranuclear inclusions (NIIs) have been identified in the brains of R6/2 mice and HID patients. One possibility is that NIIs contribute to transcriptional dysregulation by sequestering transcription factors. We therefore assessed the relationship between NIIs and transcriptional dysregulation in the R6/2 mouse, using double-label in situ hybridization combined with immunohistochemistry, and laser capture microdissection combined with quantitative real-time PCR. There was no difference in transcript levels of specific genes between NII-positive and Nil-negative neurons. These results demonstrate that NIIs do not cause decreases in D2, PPE and PSS mRNA levels in R6/2 striatum and therefore are not involved in the down-regulation of these specific genes in this HID model. In addition, these observations argue against the notion that NIIs protect against transcriptional dysregulation in HID. C1 Massachusetts Gen Hosp, 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, MassGen Inst Neurodegenerat Dis, 114 16th St,B114-2001, Charlestown, MA 02129 USA. EM cha@helix.mgh.harvard.edu OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS045242, NS038106] NR 31 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUN PY 2006 VL 23 IS 12 BP 3171 EP 3175 DI 10.1111/j.1460-9568.2006.04871.x PG 5 WC Neurosciences SC Neurosciences & Neurology GA 070EF UT WOS:000239502400003 PM 16820007 ER PT J AU Uschakov, A Gong, H McGinty, D Szymusiak, R AF Uschakov, Aaron Gong, Hui McGinty, Dennis Szymusiak, Ronald TI Sleep-active neurons in the preoptic area project to the hypothalamic paraventricular nucleus and perifornical lateral hypothalamus SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE fos; hypothalamus; lamina terminals; rat ID WAKING DISCHARGE PATTERNS; MONOAMINERGIC CELL GROUPS; EXPRESS C-FOS; LAMINA TERMINALIS; SUBFORNICAL ORGAN; AFFERENT CONNECTIONS; GALANINERGIC NEURONS; SUPRAOPTIC NUCLEUS; GABAERGIC NEURONS; HYPERTONIC SALINE AB The lamina terminalis consists of the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO) and subfornical organ. The MnPO and ventrolateral preoptic area (vIPOA) are known to contain high densities of neurons that are sleep active. The prevalence of sleep-active neurons in the OVILT and subfornical organ is unknown. The vIPOA and subdivisions of the lamina terminalis project to hypothalamic regions involved in the control of behavioral, electrographic or autonomic arousal, including the lateral hypothalamic area (LHA) and paraventricular nucleus (PVN). The extent to which projection neurons are active during sleep is unknown. We quantified c-Fos protein immunoreactivity (IR) in the lamina terminalis and vIPOA in sleeping and awake rats that received injections of retrograde tracer into either the LHA or PVN. Fos IR was also examined in lamina terminalis neurons following tracer injections into the vIPOA. Significantly more projection neurons from the MnPO, OVILT and vIPOA to the LHA were Fos-immunoreactive in sleeping vs. awake animals. Waking Fos IR was more prevalent in lamina terminalis neurons projecting to the PVN although a subset of MnPO projection neurons in sleeping rats was Fos-immunoreactive. Almost 50% of vIPOA-PVN projection neurons expressed Fos IR during sleep, compared with 3% during waking. Significantly more neurons in the OVILT and MnPO projecting to the vIPOA were Fos-immunoreactive in sleeping vs. awake rats. Inhibition of LHA and PVN neurons arising from OVILT, MnPO and vIPOA neurons may contribute to suppression of behavioral, electroencephalographic and sympathetic nervous system activation during sleep. C1 VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90024 USA. RP Szymusiak, R (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM rszym@ucla.edu FU NHLBI NIH HHS [HL60296]; NIMH NIH HHS [MH63323] NR 60 TC 31 Z9 34 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUN PY 2006 VL 23 IS 12 BP 3284 EP 3296 DI 10.1111/j.1460-9568.2006.04860.x PG 13 WC Neurosciences SC Neurosciences & Neurology GA 070EF UT WOS:000239502400014 PM 16820018 ER PT J AU Aquino, SL Kuester, LB Muse, VV Halpern, EF Fischman, AJ AF Aquino, SL Kuester, LB Muse, VV Halpern, EF Fischman, AJ TI Accuracy of transmission CT and FDG-PET in the detection of small pulmonary nodules with integrated PET/CT SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE F-18-FDG; image interpretation; computer assisted; carcinoma; metastases ID LUNG-CANCER; COMPUTED-TOMOGRAPHY; METASTASES; LESIONS; MALIGNANCY; THICKNESS; RESECTION; ARTIFACT; PROTOCOL; SYSTEM AB Purpose: The purpose of this study was to determine the accuracy of detection of small pulmonary nodules on quiet breathing attenuation correction CT (CTAC) and FDG-PET when performing integrated PET/CT, as compared with a diagnostic inspiratory CT scan acquired in the same imaging session. Methods: PET/CT scans of 107 patients with a history of carcinoma (54 male and 53 female, mean age 57.3 years) were analyzed. All patients received an integrated PET/CT scan including a CTAC acquired during quiet respiration and a contrast-enhanced CT acquired during inspiration in the same session. Breathing CTAC scans were reviewed by two thoracic radiologists for the presence of pulmonary nodules. FDG-PET scans were reviewed to determine accuracy of nodule detection. Diagnostic CT was used as the gold standard to confirm or refute the presence of nodules. Results: On the CTAC scans 200 nodules were detected, of which 183 were true positive (TP) and 17, false positive. There were 109 false negatives (FN). Overall, 51 (48%) patients had a false interpretation, including 19 in whom CT was interpreted as normal for lung nodules. The average size of the nodules missed was 3.8 +/- 2 mm (range 2-12 mm). None of the nodules missed on the CTAC scans were detected by PET. In the right lung there were 20 TP, 42 true negative (TN), 11 FP, and 34 FN interpretations with a sensitivity in nodule detection of 37% (CI 24-51%) and a specificity of 79% (CI 66-89%). In the left lungs there were 16 TP, 65 TN, 3 FP, and 23 FN interpretations, with a sensitivity of 41% (CI 26-58%) and a specificity of 96% (CI 88-99%). Conclusion: The detection of small pulmonary nodules by breathing CTAC and FDG-PET is relatively poor. Therefore an additional diagnostic thoracic CT scan obtained during suspended inspiration is recommended for thorough evaluation of those patients in whom detection of pulmonary metastases is necessary for management. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM saquino@partners.org OI Kuester, Landon /0000-0003-4850-6919 NR 29 TC 34 Z9 34 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JUN PY 2006 VL 33 IS 6 BP 692 EP 696 DI 10.1007/s00259-005-0018-x PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 049NJ UT WOS:000238023000009 PM 16514531 ER PT J AU Gupta, R Grasruck, M Suess, C Bartling, SH Schmidt, B Stierstorfer, K Popescu, S Brady, T Flohr, T AF Gupta, R Grasruck, M Suess, C Bartling, SH Schmidt, B Stierstorfer, K Popescu, S Brady, T Flohr, T TI Ultra-high resolution flat-panel volume CT: fundamental principles, design architecture, and system characterization SO EUROPEAN RADIOLOGY LA English DT Article DE CT; flat-panel detector; high resolution; volume CT; Dose ID COMPUTED-TOMOGRAPHY; TEMPORAL BONE; PREOPERATIVE ANATOMY; SCANNER AB Digital flat-panel-based volume CT (VCT) represents a unique design capable of ultra-high spatial resolution, direct volumetric imaging, and dynamic CT scanning. This innovation, when fully developed, has the promise of opening a unique window on human anatomy and physiology. For example, the volumetric coverage offered by this technology enables us to observe the perfusion of an entire organ, such as the brain, liver, or kidney, tomographically (e.g., after a transplant or ischemic event). By virtue of its higher resolution, one can directly visualize the trabecular structure of bone. This paper describes the basic design architecture of VCT. Three key technical challenges, viz., scatter correction, dynamic range extension, and temporal resolution improvement, must be addressed for successful implementation of a VCT scanner. How these issues are solved in a VCT prototype and the modifications necessary to enable ultra-high resolution volumetric scanning are described. The fundamental principles of scatter correction and dose reduction are illustrated with the help of an actual prototype. The image quality metrics of this prototype are characterized and compared with a multi-detector CT (MDCT). C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Siemens Med Solut, Forchheim, Germany. Hannover Med Sch, Dept Neuroradiol, D-3000 Hannover, Germany. RP Gupta, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders House,FND-2-216,55 Fruit St, Boston, MA 02114 USA. EM RGUPTA1@partners.org NR 16 TC 108 Z9 110 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD JUN PY 2006 VL 16 IS 6 BP 1191 EP 1205 DI 10.1007/s00330-006-0156-y PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 049OI UT WOS:000238025500001 PM 16528556 ER PT J AU Gold, PB Glynn, SM Mueser, KT AF Gold, PB Glynn, SM Mueser, KT TI Challenges to implementing and sustaining comprehensive mental health service programs SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE evidence-based practice; mental health practice and policy; psychiatric disability; dissemination; implementation ID ASSERTIVE COMMUNITY TREATMENT; RESEARCH-TEAM PORT; SUPPORTED EMPLOYMENT; TREATMENT RECOMMENDATIONS; MULTISITE DEMONSTRATIONS; FAMILY PSYCHOEDUCATION; CONCEPTUAL-MODEL; RANDOMIZED-TRIAL; FEDERAL-SUPPORT; SUBSTANCE USE AB The Presidents New Freedom Commission recently concluded that the nation's mental health service delivery system is ill equipped to meet the complex needs of persons with mental illness. A major contributor to this service quality crisis has been the long-standing divergence of research efforts and clinical programs. In this article, the authors begin by describing the unique needs of persons with serious and persisting psychiatric disorders and the evolution of the mental health service system that has attempted to meet these needs. They then discuss recent efforts to upgrade services by emphasizing the use of evidence-based practices (EBPs) and the research underlying their development. Next, they describe the difficulties of using traditional research methods to develop and test interventions for persons receiving services at public mental health agencies. Finally, they outline the challenges confronted when trying to disseminate these EBPs to the wider clinical community. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Univ Calif Los Angeles, Vet Affairs Greater Los Angeles, Los Angeles, CA 90024 USA. Dartmouth Coll Sch Med, Semel Inst Neurosci & Human Behav, Hanover, NH USA. RP Gold, PB (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA. EM goldpb@musc.edu FU NIMH NIH HHS [MH64662, MH62324, MH62629, MH01903] NR 82 TC 28 Z9 28 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD JUN PY 2006 VL 29 IS 2 BP 195 EP 218 DI 10.1177/0163278706287345 PG 24 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 041KI UT WOS:000237454700003 PM 16645184 ER PT J AU Barton, JJS Raoof, M Jameel, O Manoach, DS AF Barton, JJS Raoof, M Jameel, O Manoach, DS TI Task-switching with antisaccades versus no-go trials: a comparison of inter-trial effects SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE antisaccade; no-go; task-switching; inhibition; prosaccade ID FRONTAL EYE FIELD; ANTI-SACCADE TASK; PRO-SACCADES; INHIBITION; MOVEMENT; PLASTICITY; SELECTION; COSTS AB Antisaccades involve the suppression of a pre-potent prosaccade and a vector inversion to generate the novel ocular motor response of looking away from the target. Antisaccades have also been found to prolong the latencies of saccades in upcoming trials, an effect that we attribute to a form of immediate plasticity in the ocular motor system. Our goal was to determine whether the inter-trial effects of antisaccades were similar to that of no-go trials, where subjects must suppress making a saccade when the target appears without substituting a novel ocular motor response. We tested 12 subjects with two different blocks of saccadic trials. In one, prosaccades randomly alternated with antisaccades. In the other, prosaccades alternated with no-go trials. We analyzed the error rates and latencies of prosaccades that followed antisaccades versus no-go trials, compared to repeated prosaccades, to determine if inter-trial effects were present for both types of responses that required prosaccade suppression. No-go responses increased the error rates of prosaccades in the following trial less than antisaccades did. However, no-go trials had the same effect on the latencies of upcoming prosaccades as antisaccades. The inhibitory effect that prolongs the latencies of prosaccades after antisaccades likely stems from the need to inhibit a prosaccade, a function that is also required in no-go trials. The greater impairment of prosaccade accuracy after an antisaccade may reflect either additional control mechanisms involved in vector inversion or a different form of inhibitory control that operates during antisaccades and not during no-go responses. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Univ British Columbia, Dept Ophthalmol & Visual Sci, Div Neurol, Vancouver, BC V5Z 1M9, Canada. Aga Khan Univ, Fac Med, Karachi, Pakistan. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Athinoula A Martinos Ctr, Boston, MA 02115 USA. VGH Eye Care Ctr, Neuroophthalmol Sect D, Vancouver, BC V5Z 3N9, Canada. RP Barton, JJS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. EM jasonbarton@shaw.ca RI Barton, Jason/A-6362-2012; Raoof, Mustafa/D-1664-2012 NR 27 TC 17 Z9 17 U1 4 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 2006 VL 172 IS 1 BP 114 EP 119 DI 10.1007/s00221-005-0313-6 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 044HF UT WOS:000237662300012 PM 16369785 ER PT J AU Pedersen, WA McMillan, PJ Kulstad, JJ Leverenz, JB Craft, S Haynatzki, GR AF Pedersen, Ward A. McMillan, Pamela J. Kulstad, J. Jacob Leverenz, James B. Craft, Suzanne Haynatzki, Gleb R. TI Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice SO EXPERIMENTAL NEUROLOGY LA English DT Article DE glucocorticoids; insulin-degrading enzyme; insulin resistance; metyrapone; peroxisome proliferator-activated receptor-gamma; stress; thiazolidinedione ID INSULIN-DEGRADING ENZYME; AMYLOID BETA-PROTEIN; APOLIPOPROTEIN-E GENOTYPE; TYPE-2 DIABETES-MELLITUS; MOUSE MODEL; COGNITIVE FUNCTION; CHRONIC STRESS; DISEASE; RISK; DEMENTIA AB The thiazolidinediones, such as rosiglitazone, increase peripheral insulin sensitivity and their use is proposed for the treatment of Alzheimer's disease. However, the mechanisms underlying the potential beneficial effects of rosiglitazone in Alzheimer's disease remain unclear. In previous studies, we observed that Tg2576 Alzheimer mice develop peripheral insulin resistance with age and have much higher serum corticosterone levels than wild-type mice when fasted overnight. We further showed that both of these defects can be ameliorated by rosiglitazone administration. Here, we report that during behavioral testing which involves repetitive overnight fasting, Tg2576 mice administered rosiglitazone exhibited better spatial learning and memory abilities and had lower serum corticosterone levels than untreated Tg2576 mice. When untreated Tg2576 mice were administered metyrapone, a drug that blocks glucocorticoid production, their spatial learning and memory abilities and serum corticosterone levels were similar to those of rosiglitazone-treated mice. We further report here that rosiglitazone attenuated reductions in insulin-degrading enzyme (IDE) mRNA and activity, and reduced amyloid beta-peptide (A beta)42 levels without affecting amyloid deposition, in the brains of Tg2576 mice. These results demonstrate that rosiglitazone attenuates learning and memory deficits in Tg2576 mice and suggest that the effects of the drug on learning and memory, brain IDE levels, and brain A beta 42 levels in the mice may be due to its glucocorticoid-lowering actions. (c) 2006 Elsevier Inc. All rights reserved. C1 Creighton Univ, Med Ctr, Dept Pathol, Omaha, NE 68131 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, MIRECC, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Creighton Univ, Med Ctr, Osteoporosis Res Ctr, Dept Internal Med, Omaha, NE 68131 USA. RP Pedersen, WA (reprint author), Creighton Univ, Med Ctr, Dept Pathol, 601 N 30th St,Suite 2469, Omaha, NE 68131 USA. EM wpedersen@creighton.edu FU NIA NIH HHS [AG-10880] NR 44 TC 204 Z9 216 U1 4 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUN PY 2006 VL 199 IS 2 BP 265 EP 273 DI 10.1016/j.expneurol.2006.01.018 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 063DB UT WOS:000238995200007 PM 16515786 ER PT J AU Aperis, G Mylonakis, E AF Aperis, G Mylonakis, E TI Newer triazole antifungal agents: pharmacology, spectrum, clinical efficacy and limitations SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE albaconazole; aspergillosis; Aspergillus spp.; Candida spp.; candidaemia; candidiasis; coccidioidomycosis; cryptococcal meningitis; fusariosis; histoplasmosis; posaconazole; ravuconazole; scedosporiasis; UK-109; 496; UR-9825; voriconazole; zygomycosis ID IN-VITRO ACTIVITY; LIPOSOMAL AMPHOTERICIN-B; CELL TRANSPLANT RECIPIENTS; GUINEA-PIG MODEL; EXPERIMENTAL PULMONARY ASPERGILLOSIS; RECEIVING VORICONAZOLE PROPHYLAXIS; SCEDOSPORIUM-PROLIFICANS INFECTION; CRYPTOCOCCUS-NEOFORMANS; ECHINOCANDIN ANTIFUNGAL; FLUCONAZOLE-RESISTANT AB New triazole antifungals (voriconazole, posaconazole, ravuconazole and albaconazole) have been developed to meet the increasing need for new antifungals, and address the rising incidence of invasive fungal infections and the emergence of fungal resistance. This report describes the spectrum of activity of the newer-generation triazoles based on data from in vitro, animal and clinical studies. The authors discuss the use of these agents in combination with other antifungals, the extent of cross-resistance, their toxicity profile and pharmacokinetic proper-ties. A total of two agents are currently available: voriconazole (which is becoming a primary treatment for the management of invasive aspergillosis) and posaconazole (which demonstrates a broad antifungal spectrum). A further two agents, albaconazole and ravuconazole, are undergoing early clinical evaluation and their future is uncertain. For all newer triazoles, concerns about emerging drug-resistant fungi and the incidence and management of breakthrough infections will dictate their role in antifungal prophylaxis and treatment. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Grey Jackson 5,Room GRJ-504, Boston, MA 02114 USA. EM emylonakis@partners.org NR 173 TC 57 Z9 62 U1 0 U2 7 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUN PY 2006 VL 15 IS 6 BP 579 EP 602 DI 10.1517/13543784.15.6.579 PG 24 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 054KW UT WOS:000238376600002 PM 16732713 ER PT J AU LaRocque, RC Harris, JB Ryan, ET Qadri, F Calderwood, SB AF LaRocque, Regina C. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi Calderwood, Stephen B. TI Postgenomic approaches to cholera vaccine development SO EXPERT REVIEW OF VACCINES LA English DT Review DE cholera; comparative genomics; functional genomics; in vivo expression technology; in vivo-induced antigen technology; signature-tagged mutagenesis; transcriptional profiling; vaccines; Vibrio cholerae ID INDUCED ANTIGEN TECHNOLOGY; VIVO EXPRESSION TECHNOLOGY; TOXIN-COREGULATED PILI; VIBRIO-CHOLERAE; IMMUNE-RESPONSES; HUMAN INFECTION; CVD 103-HGR; CLINICAL CHOLERA; GENE FUSIONS; FIELD TRIAL AB Cholera remains an important public health threat. A cholera vaccine that provides durable protection at the mucosal surface, especially among children in endemic settings, is urgently needed. The availability of the complete genome sequence of a clinical isolate of Vibrio cholerae O1 El Tor has allowed for comparative and functional genomic approaches in the study of cholera. This work holds promise for the identification of bacterial targets of protective human immune responses and may contribute to the development of a new generation of cholera vaccines. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Int Ctr Diarrhoeal Dis Res, Dhaka 1212, Bangladesh. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, GRJ 504,55 Fruit St, Boston, MA 02114 USA. EM rclarocque@partners.org; jbharris@partners.org; etryan@partners.org; fqadri@icddrb.org; scalderwood@partners.org FU FIC NIH HHS [K01-TW07409, K01-TW07144]; NIAID NIH HHS [R01-AI40725, U01 AI058935, U01-AI058935] NR 71 TC 3 Z9 4 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD JUN PY 2006 VL 5 IS 3 BP 337 EP 346 DI 10.1586/14760584.5.3.337 PG 10 WC Immunology SC Immunology GA 089ZZ UT WOS:000240921700012 PM 16827618 ER PT J AU Sayers, SL White, T Zubritsky, C Oslin, DW AF Sayers, SL White, T Zubritsky, C Oslin, DW TI Family involvement in the care of healthy medical outpatients SO FAMILY PRACTICE LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-of-Behavioral-Medicine CY MAR 19-22, 2003 CL Salt Lake City, UT SP Soc Behav Med DE emotional support; family involvement; medical care; older adults ID SOCIAL SUPPORT; PRISM-E; TRIAL; INTERVENTIONS; METAANALYSIS; BEHAVIORS; OUTCOMES; LIFE AB Background. Although the involvement of patients' family members in office visits has been examined extensively, less is known about the involvement of family members in supporting patients' medical care outside of office visits. Objective. This study examines two questions: What types of family involvement do family members have in the medical care of relatively healthy older outpatients, and does self-rated health moderate patients' reactions to this family involvement? Methods. Patients from a large sample of medical practice outpatients (N = 1572) were assessed to determine perceived emotional support, involvement of family members in their medical care, as well as the presence of depressive symptoms. Results. Approximately 50% of patients had some family involvement in their medical care (e.g. taking part in medical decisions, reminding the patient to take medication). Marital status was a stronger predictor of family involvement than self-ratings of poor physical health. Additionally, there was no evidence that older patients who report good health have less favourable reactions to family involvement in their medical care. Conclusion. Family involvement in medical care occurs routinely and is most likely to involve a spouse, and is consistent with family interaction patterns among older adults. These findings also suggest that when providers invite family members to support treatment outside the office visit, these invitations are appropriate for older adult patients across a continuum of good to poor health. C1 Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Res Educ & Clin Ctr, VISN Mental Illness 4, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. RP Sayers, SL (reprint author), Vet Affairs Med Ctr, 116,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM ssayers@mail.med.upenn.edu FU NIMH NIH HHS [1K08 MH01599]; PHS HHS [1UDISM53033] NR 24 TC 21 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0263-2136 J9 FAM PRACT JI Fam. Pr. PD JUN PY 2006 VL 23 IS 3 BP 317 EP 324 DI 10.1093/fampra/cmi114 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 048EY UT WOS:000237931600010 PM 16461451 ER PT J AU Zhang, M Haapasalo, A Kim, DY Ingano, LAM Pettingell, WH Kovacs, DM AF Zhang, Mei Haapasalo, Annakaisa Kim, Doo Yeon Ingano, Laura A. MacKenzie Pettingell, Warren H. Kovacs, Dora M. TI Presenilin/gamma-secretase activity regulates protein clearance from the endocytic recycling compartment SO FASEB JOURNAL LA English DT Article DE amyloid precursor protein; transferrin; trafficking; Alzheimer's disease; neurodegeneration ID AMYLOID PRECURSOR PROTEIN; SPORADIC ALZHEIMERS-DISEASE; P75 NEUROTROPHIN RECEPTOR; HAMSTER OVARY CELLS; TRANS-GOLGI NETWORK; GAMMA-SECRETASE; PLASMA-MEMBRANE; BETA-SECRETASE; E-CADHERIN; INTRACELLULAR DOMAIN AB The presenilin (PS)/gamma-secretase complex proteolytically cleaves more than 20 different proteins in addition to the amyloid precursor protein (APP). These substrates are almost exclusively type I membrane proteins. Many undergo internalization from the cell surface followed by degradation or recycling back to the plasma membrane through the endocytic recycling compartment (ERC). Evidence shows that the PSs also regulate intracellular trafficking of APP and its C-terminal fragments (CTFs). To investigate whether PS/gamma-secretase activity is required for normal endosomal recycling, we performed live cell imaging experiments with fluorescently labeled transferrin, reported to specifically traffic through the ERC. By using pharmacological gamma-secretase inhibitors or cell lines lacking functional PS/gamma-secretase, here we show that PS/gamma-secretase activity is required for clearance of transferrin from the ERC. Interestingly, lack of PS/gamma-secretase function also resulted in the accumulation of APP and APP-CTFs in the ERC in addition to the cell surface. Familial Alzheimer's disease mutations in APP-CTFs did not affect endocytic recycling of these proteins. Our results suggest that PS/gamma-secretase activity is required for normal endosomal recycling of soluble and membrane- associated proteins through the ERC and propose a new mechanism by which impaired PS/gamma-secretase function may eventually contribute to neurodegeneration. C1 Synta Pharmaceut Corp, Lexington, MA 02421 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Neurol,MIND, Neurobiol Dis Lab,Genet & Aging Res Unit, Charlestown, MA USA. RP Kovacs, DM (reprint author), Synta Pharmaceut Corp, 45 Hartwell Ave, Lexington, MA 02421 USA. EM dora_kovacs@hms.harvard.edu NR 96 TC 36 Z9 37 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 2006 VL 20 IS 8 BP 1176 EP + DI 10.1096/fj.05-5531fje PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 079XD UT WOS:000240210300017 PM 16645046 ER PT J AU Sotiropoulos, KB Clermont, A Yasuda, Y Rask-Madsen, C Mastumoto, M Takahashi, J Della Vecchia, K Kondo, T Aiello, LP King, GL AF Sotiropoulos, Konstantinos B. Clermont, Allen Yasuda, Yutaka Rask-Madsen, Christian Mastumoto, Motonobu Takahashi, Junichi Della Vecchia, Kim Kondo, Tatsuya Aiello, Lloyd P. King, George L. TI Adipose-specific effect of rosiglitazone on vascular permeability and protein kinase C activation: novel mechanism for PPAR gamma agonist's effects on edema and weight gain SO FASEB JOURNAL LA English DT Article DE Zucker diabetic fatty rat; ruboxistaurin; vascular endothelial growth factor; insulin receptor knockout mice; thiazolidinedione ID ENDOTHELIAL GROWTH-FACTOR; TIGHT JUNCTION PERMEABILITY; DIABETIC-RATS; INSULIN-RESISTANCE; GENE-EXPRESSION; RETINAL NEOVASCULARIZATION; FLUID RETENTION; SKELETAL-MUSCLE; THIAZOLIDINEDIONE; BETA AB PPAR gamma agonists, thiazolidinediones, cause fluid retention and edema due to unknown mechanisms. We characterized the effect of rosiglitazone (RSG), a thiazolidinedione, to induce vascular permeability, vascular endothelial growth factor (VEGF) expression, and protein kinase C (PKC) activation with edema and wt gain. In lean, fatty and diabetic Zucker rats, and endothelial insulin receptor knockout mice, RSG increased wt and vascular permeability, selectively in fat and retina, but not in heart or skeletal muscle. H2O content and wt of epididymal fat were increased by RSG and correlated to increases in capillary permeability in fat and body wt. RSG induced VEGF mRNA expression and PKC activation in fat and retina up to 2.5-fold. Ruboxistaurin, a PKC beta isoform inhibitor, in the latter 2 wk of a 4-wk study, normalized vascular permeability in fat and decreased total wt gain, H2O content, and wt of fat vs. RSG alone but did not decrease VEGF expression, basal permeability, or food intake. Finally, RSG did not increase wt or vascular permeability in PKC beta knockout vs. control mice. Thus, thiazolidinedione's effects on edema and wt are partially due to an adipose tissue-selective activation of PKC and vascular permeability that may be prevented by PKC beta inhibition. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu FU NEI NIH HHS [EY05110] NR 46 TC 58 Z9 60 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 2006 VL 20 IS 8 BP 1203 EP + DI 10.1096/fj05-4617fje PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 079XD UT WOS:000240210300026 PM 16672634 ER PT J AU Linglart, A Mahon, MJ Dean, T Gardella, TJ Jueppner, H Bastepe, M AF Linglart, A. Mahon, M. J. Dean, T. Gardella, T. J. Jueppner, H. Bastepe, M. TI Human XL alpha s signals more efficiently than the alpha-subunit of the stimulatory G protein (GS alpha) in vitro SO FEBS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUN 24-29, 2006 CL Istanbul, TURKEY SP Federat European Biochem Soc C1 Hop St Vincent de Paul, INSERM, U561, F-75674 Paris, France. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu 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 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2006 VL 273 SU 1 BP 45 EP 45 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZR UT WOS:000238914000147 ER PT J AU Dirice, E Sanlioglu, AD Omer, A Balci, MK Terzioglu, E Sanlioglu, S AF Dirice, E. Sanlioglu, A. D. Omer, A. Balci, M. K. Terzioglu, E. Sanlioglu, S. TI Adenovirus mediated TRAIL gene delivery as a model for the treatment of patients with diabetes SO FEBS JOURNAL LA English DT Meeting Abstract CT 31st Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUN 24-29, 2006 CL Istanbul, TURKEY SP Federat European Biochem Soc C1 Akdeniz Univ, Fac Med, Dept Humane Gene Therapy, Antalya, Turkey. Akdeniz Univ, Fac Med, Dept Med Biol Genet, Antalya, Turkey. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. EM dercument@akdeniz.edu.tr RI terzioglu, ender/B-9180-2016; BALCI, Mustafa Kemal/C-2979-2016; Sanlioglu, Salih/F-9305-2016 OI BALCI, Mustafa Kemal/0000-0002-6494-3249; NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2006 VL 273 SU 1 BP 206 EP 206 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZR UT WOS:000238914001300 ER PT J AU London, R Orozco, BS Mylonakis, E AF London, R Orozco, BS Mylonakis, E TI The pursuit of cryptococcal pathogenesis: heterologous hosts and the study of cryptococcal host-pathogen interactions SO FEMS YEAST RESEARCH LA English DT Review DE Caenorhabditis elegans; Cryptococcus neoformans; Drosophila melanogaster; fungal infection; Galleria mellonella; Toll-pathway ID GALLERIA-MELLONELLA LARVAE; CANDIDA-ALBICANS MUTANTS; INNATE IMMUNE-RESPONSE; CAENORHABDITIS-ELEGANS; VIRULENCE FACTORS; DROSOPHILA-MELANOGASTER; ASPERGILLUS-FUMIGATUS; NEOFORMANS; MODEL; PROTEIN AB Analysis of the molecular mechanisms by which a pathogen interacts with the human host is most commonly performed using a mammalian model of infection. However, several virulence-related genes previously shown to be involved in mammalian infection with Cryptococcus neoformans have also been shown to play a role in the interaction of these pathogens with invertebrates, such as Acanthamoeba castellanii, Caenorhabditis elegans, Dictyostelium discoideum, Drosophila melanogaster and Galleria mellonella. The study of host-pathogen interactions using these model hosts has allowed rapid screening of mutant libraries and can be used for the study of evolutionarily preserved aspects of microbial virulence and host response. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIAID NIH HHS [AI63084-01] NR 36 TC 21 Z9 24 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1567-1356 J9 FEMS YEAST RES JI FEMS Yeast Res. PD JUN PY 2006 VL 6 IS 4 BP 567 EP 573 DI 10.1111/j.1567-1364.2006.00056.x PG 7 WC Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biotechnology & Applied Microbiology; Microbiology; Mycology GA 042GX UT WOS:000237517100012 PM 16696652 ER PT J AU Muller, FL Song, W Liu, YH Chaudhuri, A Pieke-Dahl, S Strong, R Huang, TT Epstein, CJ Roberts, LJ Csete, M Faulkner, JA Van Remmen, H AF Muller, FL Song, W Liu, YH Chaudhuri, A Pieke-Dahl, S Strong, R Huang, TT Epstein, CJ Roberts, LJ Csete, M Faulkner, JA Van Remmen, H TI Absence of CuZn superoxide dismutase leads to elevated oxidative stress and acceleration of age-dependent skeletal muscle atrophy SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE superoxide; muscle atrophy; aging; oxidative stress; CuZnSOD; free radicals ID INTERMEMBRANE SPACE; LIPID-PEROXIDATION; REACTIVE OXYGEN; DEFICIENT MICE; MOTOR-NEURONS; NULL MUTATION; HEARING-LOSS; COMPLEX-III; FIBER TYPES; DROSOPHILA AB We describe a novel phenotype in mice lacking the major antioxidant enzyme, CuZn-superoxide dismutase (Sod1(-/-) mice), namely a dramatic acceleration of age-related loss of skeletal muscle mass. Sod1(-/-) mice are 17 to 20% smaller and have a significantly lower muscle mass than wildtype mice as early as 3 to 4 months of age. Muscle mass in the Sod1(-/-) mice is further reduced with age and by 20 months, the hind-limb muscle mass in Sod1(-/-) mice is nearly 50% lower than in age-matched wild-type mice. Skeletal muscle tissue from young Sod1(-/-) mice has elevated oxidative damage to proteins, lipids, and DNA compared to muscle from young wild-type mice. The reduction in muscle mass and elevated oxidative damage are accompanied by a 40% decrease in voluntary wheel running by 6 months of age and decreased performance on the Rota-rod test at 13 months of age, but are not associated with a decline in overall spontaneous activity. In some of the old Sod1(-/-) mice, the loss in muscle mass is also associated with the presence of tremors and gait disturbances. Thus, the absence of CuZnSOD imposes elevated oxidative stress, loss of muscle mass, and physiological consequences that resemble an acceleration of normal age-related sarcopenia. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Vanderbilt Univ, Dept Pharmacol & Med, Nashville, TN 37232 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. RP Van Remmen, H (reprint author), Univ Texas, Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr,MSC 7762, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu FU NIA NIH HHS [5T3-AG021890-02, P01 AG20591]; NIGMS NIH HHS [GM42056] NR 55 TC 188 Z9 194 U1 1 U2 13 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 JUN 1 PY 2006 VL 40 IS 11 BP 1993 EP 2004 DI 10.1016/j.freeradbiomed.2006.01.036 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 050QP UT WOS:000238103300012 PM 16716900 ER PT J AU Goodgame, R Graham, DY AF Goodgame, Richard Graham, David Y. TI Common gastrointestinal and hepatic infections - Preface SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Baylor Coll Med, Houston, TX 77030 USA. Vet Affairs Med Ctr 111D, Houston, TX 77030 USA. RP Goodgame, R (reprint author), Baylor Coll Med, 1 Baylor Plaza,Room 525-D, Houston, TX 77030 USA. EM goodgame@bcm.tmc.edu; dgraham@bcm.tmc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2006 VL 35 IS 2 BP XIII EP XIV DI 10.1016/j.gtc.2006.05.004 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 076PI UT WOS:000239969800001 ER PT J AU Vilaichone, RK Mahachai, V Graham, DY AF Vilaichone, Ratha-Korn Mahachai, Varocha Graham, David Y. TI Helicobacter pylori diagnosis and management SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; RANITIDINE BISMUTH CITRATE; PROTON PUMP INHIBITORS; QUADRUPLE THERAPY; UNITED-STATES; SEQUENTIAL TREATMENT; INFECTED PERSONS; GASTRIC-CANCER; ULCER DISEASE; PEPTIC-ULCER AB Helicobacter pylori is a global human pathogen and the major cause of gastritis and the gastritis-associated diseases: gastric ulcer, duodenal ulcer, gastric cancer, and primary gastric B-cell lymphoma. Although several reliable diagnostic tests are widely available, the ideal regimen for treating the infection remains to be established. The current first-line or legacy triple therapy regimens fail in 20% to 40% of patients. Recent studies have confirmed older observations that the success rate of legacy triple regimens (proton pump inhibitor plus two antibiotics) can be improved if the duration is extended to 14 days or a third antibiotic is given. Confirmation of eradication using noninvasive diagnostic tests, such as a urea breath test or stool antigen assay, is now the standard of care. C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Thammasat Univ Hosp, Gastroenterol Unit, Dept Med, Pathum Thani 12120, Thailand. Chulalongkorn Univ Hosp, Dept Med, Div Gastroenterol, Bangkok 10330, Thailand. Baylor Coll Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU NIDDK NIH HHS [DK56338] NR 87 TC 43 Z9 52 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2006 VL 35 IS 2 BP 229 EP + DI 10.1016/j.gtc.2006.03.004 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 076PI UT WOS:000239969800002 PM 16880064 ER PT J AU Aslam, S Musher, DM AF Aslam, Saima Musher, Daniel M. TI An update on diagnosis, treatment, and prevention of Clostridium difficile - Associated disease SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review ID ANTIBIOTIC-ASSOCIATED COLITIS; PLACEBO-CONTROLLED TRIAL; CLINDAMYCIN-ASSOCIATED COLITIS; RANDOMIZED CONTROLLED-TRIAL; PROTON PUMP INHIBITORS; IN-VITRO ACTIVITY; TOX A/B TEST; PSEUDOMEMBRANOUS COLITIS; DOUBLE-BLIND; HOSPITALIZED-PATIENTS AB Clostridium diffiicile is an Important cause of nosocomial morbidity and mortality and is implicated in recent epidemics. Data support the treatment of colitis with oral metronidazole in a dose of 1.0 to 1.5 g/d, with oral vancomycin as a second-line agent. Given recent data regarding poorer response rates than previously described and more severe disease, alternative agents for the treatment of initial and recurrent disease are being studied. Greater attention should be paid to hospital infection control policies and restriction of broad-spectrum antibiotics. C1 Michael E DeBakey Vet Affairs Med Ctr, Med Serv, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Aslam, S (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Med Serv, Infect Dis Sect, Room 4B-370,2002 Holcombe Blvd, Houston, TX 77030 USA. EM saslam@bcm.tmc.edu NR 179 TC 41 Z9 48 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 2006 VL 35 IS 2 BP 315 EP + DI 10.1016/j.gtc.2006.03.009 PG 22 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 076PI UT WOS:000239969800006 PM 16880068 ER PT J AU Groisman, R Kuraoka, I Chevallier, O Gaye, N Magnaldo, T Tanaka, K Kisselev, AF Harel-Bellan, A Nakatani, Y AF Groisman, Regina Kuraoka, Isao Chevallier, Odile gaye, No Gaye Magnaldo, Thierry Tanaka, Kiyoji Kisselev, Alexei F. Harel-Bellan, Annick Nakatani, Yoshihiro TI CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome SO GENES & DEVELOPMENT LA English DT Article DE CSB; CSA; ubiquitin-proteasomal degradation ID RNA-POLYMERASE-II; COUPLING FACTOR CSB/ERCC6; B REPAIR PROTEIN; DNA-REPAIR; COP9 SIGNALOSOME; TRANSCRIPTION; COMPLEXES; ELONGATION; DEFICIENT; LIGASES AB Mutations in the CSA or CSB complementation genes cause the Cockayne syndrome, a severe genetic disorder that results in patients' death in early adulthood. CSA and CSB act in a transcription-coupled repair (TCR) pathway, but their functional relationship is not understood. We have previously shown that CSA is a subunit of an E3 ubiquitin ligase complex. Here we demonstrate that CSB is a substrate of this ligase: Following UV irradiation, CSB is degraded at a late stage of the repair process in a proteasome- and CSA-dependent manner. Moreover, we demonstrate the importance of CSB degradation for post-TCR recovery of transcription and for the Cockayne syndrome. Our results unravel for the first time the functional relationship between CSA and CSB. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. CNRS, Ligue Natl Contre Canc, UPR9079, F-94800 Villejuif, France. Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. Dartmouth Med Sch, Dept Pharmacol & Toxicol, Lebanon, NH 03756 USA. Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan. Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol, Suita, Osaka 5650871, Japan. Inst Gustave Roussy, CNRS, UPR2169, Lab Genet Instabil & Canc, F-94805 Villejuif, France. RP Groisman, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM groisman@vjf.cnrs.fr RI Harel-Bellan, Annick/M-9795-2015; OI Harel-Bellan, Annick/0000-0002-2339-153X NR 28 TC 126 Z9 133 U1 1 U2 5 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 JUN 1 PY 2006 VL 20 IS 11 BP 1429 EP 1434 DI 10.1101/gad.378206 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 052ZV UT WOS:000238273700005 PM 16751180 ER PT J AU Gimelbrant, AA Chess, A AF Gimelbrant, AA Chess, A TI An epigenetic state associated with areas of gene duplication SO GENOME RESEARCH LA English DT Article ID MONOALLELICALLY EXPRESSED GENES; ASYNCHRONOUS REPLICATION; ALLELIC EXCLUSION; DNA-REPLICATION; MOUSE; CELLS; CHROMOSOMES; RECEPTORS; TISSUES; SYSTEM AB Asynchronous DNA replication is an epigenetically determined feature found in all cases of monoallelic expression, including genomic imprinting, X-inactivation, and random monoallelic expression of autosomal genes such as immunoglobulins and olfactory receptor genes. Most genes of the latter class were identified in experiments focused on genes functioning in the chemosensory and immune systems. We performed an unbiased survey of asynchronous replication in the mouse genome, excluding known asynchronously replicated genes. Fully 10% (eight of 80) of the genes tested exhibited asynchronous replication. A common feature of the newly identified asynchronously replicated areas is their proximity to areas of tandem gene duplication. Testing of other clustered areas supported the idea that such regions are enriched with asynchronously replicated genes. C1 Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Chess, A (reprint author), Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM chess@chgr.mgh.harvard.edu NR 32 TC 20 Z9 20 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUN PY 2006 VL 16 IS 6 BP 723 EP 729 DI 10.1101/gr.5023706 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 048UY UT WOS:000237973200004 PM 16687731 ER PT J AU Luxameechanporn, T Hadlock, T Shyu, J Cowan, D Faquin, W Varvares, M AF Luxameechanporn, T Hadlock, T Shyu, J Cowan, D Faquin, W Varvares, M TI Successful myoblast transplantation in rat tongue reconstruction SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE tongue; tissue engineering; myoblasts ID DUCHENNE MUSCULAR-DYSTROPHY; MEDIATED GENE-THERAPY; SKELETAL-MUSCLE; MDX MICE; IMMUNE-REACTIONS; MYOGENIC CELLS; MOUSE MUSCLES; ALLOTRANSPLANTATION; 5-BROMODEOXYURIDINE; REGENERATION AB Background, Controversy exists regarding the success of myoblast transplantation. The purpose of this study was to determine the survival of transplanted myoblasts in a rat tongue reconstruction model by using fluorescently labeled myoblasts and surgical stains to mark the location of the pocket into which transplanted cells were delivered. We evaluated tongue histology after myoblast transplantation under the hypothesis that myoblast transplantation will promote muscle regeneration and result in minimal scar tissue formation. Methods. Sterile solutions of 1:10 India ink, 1% methylene blue, and 1% crystal violet were applied to the inner lining of a left-sided mucosa-sparing hemiglossectomy pocket. After air-drying, the hemiglossectomy defect was filled with collagen gel and closed. The tongues were evaluated histologically at 6 weeks. Next, myoblasts were cultured and labeled with three commercially available fluorescent dyes, 5-chloromethyl-fluorescein diacetate (CMFDA), chloromethylbenzamido (CM-Dil), and fluorescently labeled microspheres (FLMs), to determine which would optimally label myoblasts in a tongue reconstruction model. Next, Lewis rats underwent left hemiglossectomy, and the created pockets were coated with 1:10 India ink. Control animals received collagen gel alone, whereas experimental animals received labeled myoblast/collagen constructs into the tongue defect. Tongues were harvested at intervals to determine the presence of labeled fluorescent cells, the relative numbers of viable myoblasts, and the degree of scarring. Results. India ink coating of the hemiglossectomy pocket caused minimal inflammation and lasted longer than the other tested dyes. CMFDA and FLMs both successfully label myoblasts for transplantation. In vivo, donor cells were observed in all specimens at week 0 with increasing numbers of cells and muscle formation, determined by desmin immunofluorescence, after 6 weeks. There was less scar tissue contracture in the experimental group and a significant increase in the amount of desmin-stained muscle in the surgical defect. Conclusions. India ink is an appropriate vehicle for intra-operative marking of a hemiglossectomy cavity. The introduction of myoblast/collagen constructs into the rat hemiglossectomy defect increases the amount of regenerated muscle, results in less scar contracture, and may increase meaningful tongue function. (c) 2006 Wiley Periodicals, Inc. C1 St Louis Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63110 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Childrens Hosp, Med Ctr, Lab Cardiac Muscle Physiol, Boston, MA 02115 USA. RP Varvares, M (reprint author), St Louis Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, 3635 Vista Ave Grand,POB 15250, St Louis, MO 63110 USA. EM varvares@slu.edu FU NHLBI NIH HHS [R01 HL068915] NR 44 TC 7 Z9 7 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD JUN PY 2006 VL 28 IS 6 BP 517 EP 524 DI 10.1002/hed.20325 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 049UI UT WOS:000238042400006 PM 16619280 ER PT J AU Mulley, AG AF Mulley, AG TI Health policy in Britain SO HEALTH EXPECTATIONS LA English DT Book Review C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Mulley, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 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 1369-6513 J9 HEALTH EXPECT JI Health Expect. PD JUN PY 2006 VL 9 IS 2 BP 191 EP 192 DI 10.1111/j.1369-7625.2006.00367.x PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 040AT UT WOS:000237351400011 ER PT J AU Graham, DY Uemura, N AF Graham, DY Uemura, N TI Natural history of gastric cancer after Helicobacter pylori eradication in Japan: After endoscopic resection, after treatment of the general population, and naturally SO HELICOBACTER LA English DT Editorial Material ID SUBSEQUENT DEVELOPMENT; BIRTH COHORT; INFECTION; EPIDEMIOLOGY; CHILDREN; REGION C1 Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Mol Virol & Microbiol, Houston, TX USA. Int Med Ctr Japan, Dept Gastroenterol, Shinjyu Ku, Tokyo, Japan. RP Graham, DY (reprint author), Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. EM dgraham@bcm.tmc.edu FU NIDDK NIH HHS [DK56338] NR 24 TC 10 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD JUN PY 2006 VL 11 IS 3 BP 139 EP 143 DI 10.1111/j.1523-5378.2006.00391.x PG 5 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 040QK UT WOS:000237395300001 PM 16684259 ER PT J AU Sterling, RK Lissen, E Clumeck, N Sola, R Correa, MC Montaner, J Sulkowski, MS Torriani, FJ Dieterich, DT Thomas, DL Messinger, D Nelson, M AF Sterling, RK Lissen, E Clumeck, N Sola, R Correa, MC Montaner, J Sulkowski, MS Torriani, FJ Dieterich, DT Thomas, DL Messinger, D Nelson, M CA APRICOT Clinical Investigators TI Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection SO HEPATOLOGY LA English DT Article; Proceedings Paper CT 12th Conference on Retroviruses and Opportunistic Infections CY FEB 22-25, 2005 CL Boston, MA ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; HIV-INFECTED PATIENTS; LIVER FIBROSIS; BIOCHEMICAL MARKERS; ASPARTATE-AMINOTRANSFERASE; SERUM MARKERS; BIOPSY; CIRRHOSIS AB Liver biopsy remains the gold standard in the assessment of severity of liver disease. Noninvasive tests have gained popularity to predict histology in view of die associated risks of biopsy. However, many models include tests not readily available, and there are limited data from patients with HIV/hepatitis C virus (HCV) coinfection. We aimed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection. A retrospective analysis of liver histology was performed in 832 patients. Liver fibrosis was assessed via Ishak score; patients were categorized as 0-1, 2-3, or 4-6 and were randomly assigned to training (n = 555) or validation (n = 277) sets. Multivariate logistic regression analysis revealed that platelet count (PLT), age, AST, and M were significantly associated with fibrosis. Additional analysis revealed PLT, age, AST, and ALT as an alternative model. Based on this, a simple index (FIB-4) was developed: age ([yr] x AST [U/L])/((PLT [10(9)/L]) X (ALT [U/L])(1/2)). The AUROC of the index was 0.765 for differentiation between Ishak stage 0-3 and 4-6. At a cutoff of < 1.45 in the validation set, the negative predictive value to exclude advanced fibrosis (stage 4-6) was 90% with a sensitivity of 70%. A cutoff of > 3.25 had a positive predictive value of 65% and a specificity of 97%. Using these cutoffs, 87% of the 198 patients with FIB-4 values outside 1.45-3.25 would be correctly classified, and liver biopsy could be avoided in 71% of the validation group. In conclusion noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients. C1 Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. Virgen Rocio Univ Hosp, Seville, Spain. CHU St Pierre, Brussels, Belgium. Univ Autonoma Barcelona, Hosp del Mar, Liver Sect, Barcelona, Spain. HCFMUSP Casa AIDS, Sao Paulo, Brazil. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Univ Calif San Diego, Treatment Ctr, San Diego, CA 92103 USA. Mt Sinai Sch Med, New York, NY USA. IST GmbH, Mannheim, Germany. Chelsea & Westminster Hosp, London, England. RP Sterling, RK (reprint author), Virginia Commonwealth Univ Hlth Syst, Sect Hepatol, W Hosp, 1200 E Broad St,Room 1492, Richmond, VA 23298 USA. EM rksterli@hsc.vcu.edu RI Manzotti, Grazia/C-5985-2008; mendes correa, maria cassia /A-6779-2013 FU NIDA NIH HHS [R01DA16078]; NIDDK NIH HHS [K23 DK064578] NR 48 TC 665 Z9 680 U1 3 U2 11 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 2006 VL 43 IS 6 BP 1317 EP 1325 DI 10.1002/hep.21178 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 048ZG UT WOS:000237984500018 PM 16729309 ER PT J AU Pekkola, J Ojanen, V Autti, T Jaaskelainen, IP Mottonen, R Sams, M AF Pekkola, J Ojanen, V Autti, T Jaaskelainen, IP Mottonen, R Sams, M TI Attention to visual speech gestures enhances hernodynamic activity in the left planum temporale SO HUMAN BRAIN MAPPING LA English DT Article DE speech perception; attention; audiovisual; crossmodal; auditory cortex; planum temporale ID AUDITORY-CORTEX ACTIVATION; AUDIOVISUAL SPEECH; SELECTIVE ATTENTION; FMRI; PERCEPTION; MODULATION; LANGUAGE; CORTICES; STIMULI; HUMANS AB Observing a speaker's articulatory gestures can contribute considerably to auditory speech perception. At the level of neural events, seen articulatory gestures can modify auditory cortex responses to speech sounds and modulate auditory cortex activity also in the absence of heard speech. However, possible effects of attention on this modulation have remained unclear. To investigate the effect of attention on visual speech-induced auditory cortex activity, we scanned 10 healthy volunteers with functional magnetic resonance imaging (fMRI) at 3 T during simultaneous presentation of visual speech gestures and moving geometrical forms, with the instruction to either focus on or ignore the seen articulations. Secondary auditory cortex areas in the bilateral posterior superior temporal gyrus and planum temporale were active both when the articulatory gestures were ignored and when they were attended to. However, attention to visual speech gestures enhanced activity in the left planum temporale compared to the situation when the subjects saw identical stimuli but engaged in a nonspeech motion discrimination task. These findings suggest that attention to visually perceived speech gestures modulates auditory cortex function and that this modulation takes place at a hierarchically relatively early processing level. C1 Univ Helsinki, Cent Hosp, Dept Radiol, Helsinki Med Imaging Ctr, FIN-00029 Helsinki, Finland. Helsinki Univ Technol, Lab Compuatat Engn, FIN-02150 Espoo, Finland. Helsinki Univ Technol, Adv Magnet Imaging Ctr, FIN-02150 Espoo, Finland. Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, MIT,Massachusetts Gen Hosp, Charlestown, MA USA. RP Pekkola, J (reprint author), Univ Helsinki, Cent Hosp, Dept Radiol, Helsinki Med Imaging Ctr, POB 340, FIN-00029 Helsinki, Finland. EM johanna.pekkola@fimnet.fi RI Jaaskelainen, Iiro/C-7392-2012; Sams, Mikko/G-7060-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; FU NICHD NIH HHS [R01-HD040712] NR 35 TC 40 Z9 42 U1 1 U2 3 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 2006 VL 27 IS 6 BP 471 EP 477 DI 10.1002/hbm.20190 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 046LV UT WOS:000237814000001 PM 16161166 ER PT J AU Qi, L van Dam, RM Meigs, JB Manson, JE Hunter, D Hu, FB AF Qi, L van Dam, RM Meigs, JB Manson, JE Hunter, D Hu, FB TI Genetic variation in IL6 gene and type 2 diabetes: tagging-SNP haplotype analysis in large-scale case-control study and meta-analysis SO HUMAN MOLECULAR GENETICS LA English DT Article ID G/C PROMOTER POLYMORPHISM; BODY-MASS INDEX; INTERLEUKIN-6 GENE; INFLAMMATORY MARKERS; INSULIN SENSITIVITY; PLASMA-LEVELS; IL-6 GENE; TNF-ALPHA; MELLITUS; ASSOCIATION AB Interleukin-6 (IL-6, gene symbol IL6) is a proinflammatory cytokine. High circulating IL-6 levels have been associated with insulin resistance and greater risk of type 2 diabetes. Using a linkage disequilibrium (LD)-based approach, we sought to investigate the associations of the common polymorphisms comprehensively defining the genetic variability at the IL6 locus with diabetes risk. We conducted a case-control study of 2691 cases of type 2 diabetes (1692 women and 999 men) and 3237 control subjects (2238 women and 999 men) from the Nurses' Health Study and the Health Professional Follow-up Study. Pairwise LD analysis indicated that all the IL6 polymorphisms (rs2069827, rs1800797, rs1800795, rs1554606, rs2069849, rs2069861 and rs1818879) were in strong LD. We did not find significant associations between IL6 polymorphisms and the risk of type 2 diabetes in women or men, individually or in haplotypes. In addition, none of the IL6 polymorphisms was significantly associated with the plasma levels of IL-6 in the control subjects. Our meta-analysis of 5383 diabetes case and 12 069 controls indicated a null association between the best-studied 5' promoter polymorphism -174G > C (rs1800795) and diabetes risk. Diversity in adiposity, age and sex could not account for the heterogeneity across different studies. In summary, the data in this study do not support substantial associations between the common polymorphisms in IL6 gene and circulating IL-6 levels and the risk of type 2 diabetes. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM nhlqi@channing.harvard.edu; frank.hu@channing.harvard.edu RI van Dam, Rob/F-9674-2010 OI van Dam, Rob/0000-0002-7354-8734 FU NCI NIH HHS [CA 87969]; NIDDK NIH HHS [DK 58845] NR 35 TC 67 Z9 70 U1 0 U2 5 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 2006 VL 15 IS 11 BP 1914 EP 1920 DI 10.1093/hmg/ddl113 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 044UA UT WOS:000237696700017 PM 16644865 ER PT J AU Farabaugh, AH Sonawalla, SB Fava, M Pedrelli, P Papakostas, GI Schwartz, F Mischoulon, D AF Farabaugh, Amy H. Sonawalla, Shamsah B. Fava, Maurizio Pedrelli, Paola Papakostas, George I. Schwartz, Faye Mischoulon, David TI Differences in cognitive factors between "true drug" versus "placebo pattern" response to fluoxetine as defined by pattern analysis SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article DE TDR; PPR; cognitive factors; depression; perceived stress ID PERCEIVED STRESS; DEPRESSION; ANTIDEPRESSANTS; DISORDER; SUBTYPES; TRIALS; AXIS AB Objective Pattern analysis has identified two types of response patterns to antidepressants: "true drug" response (TDR) and "placebo pattern" response (PPR). This study examines the relationship between cognitive factors and TDR and PPR to fluoxetine. Methods We assessed 310 outpatients meeting DSM-III-R criteria for major depressive disorder (MDD) who were enrolled in an 8-week open trial of fluoxetine 20 mg/day. Response patterns were determined Using the clinical global impressions-improvement (CGI-I). We administered the following self-rated scales to all patients at the baseline visit and at endpoint: perceived stress scale (PSS), cognitions questionnaire (CQ), Beck hopelessness scale (BHS) and dysfunctional attitudes scale (DAS). Results One hundred and thirty-four patients had TDR, 66 patients had PPR, and 110 patients were non-responders (NR). Demographic variables and severity of depression at baseline (HAMD-17) were not significantly different between the two response pattern groups. We compared cognitive factors before and after treatment across patients with TDR and PPR, and there were no significant differences at baseline in CQ, PSS, BHS, and DAS scores. At endpoint, outpatients with PPR had significantly lower scores on the PSS (p < 0.001) compared to the patients with TDR, even after adjusting for multiple comparisons and severity of depression at endpoint. Conclusions Significant differences in cognitive/psychological factors, specifically lower post-treatment perceived stress, accompany "placebo" pattern of response to antidepressant treatment and differentiate it from "true drug" response pattern, as defined by pattern analysis. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02115 USA. RP Farabaugh, AH (reprint author), 15 Parkman St, Boston, MA 02114 USA. EM afarabaugh@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 23 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD JUN PY 2006 VL 21 IS 4 BP 221 EP 225 DI 10.1002/hup.765 PG 5 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 063SD UT WOS:000239039000002 PM 16783809 ER PT J AU Becker, CM Wright, RD Satchi-Fainaro, R Funakoshi, T Folkman, J Kung, AL D'Amato, RJ AF Becker, C. M. Wright, R. D. Satchi-Fainaro, R. Funakoshi, T. Folkman, J. Kung, A. L. D'Amato, R. J. TI A novel non-invasive mouse model of endometriosis for monitoring angiogenesis and the efficacy of anti-angiogenic therapy SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 22nd Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology CY JUN 18-21, 2006 CL Prague, CZECH REPUBLIC SP European Soc Human Reproduct & Embryol C1 Univ Oxford, Nuffield Dept Obstet Gynecol, Oxford, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, Boston, Israel. Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. RI Satchi-Fainaro, Ronit/F-9137-2011 OI Satchi-Fainaro, Ronit/0000-0002-7360-7837 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 2006 VL 21 SU 1 BP I183 EP I183 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 062PO UT WOS:000238957200467 ER PT J AU Sasaki, Y Derudder, E Hobeika, E Pelanda, R Reth, M Rajewsky, K Schmidt-Supprian, M AF Sasaki, Y Derudder, E Hobeika, E Pelanda, R Reth, M Rajewsky, K Schmidt-Supprian, M TI Canonical NF-kappa B activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation SO IMMUNITY LA English DT Article ID LYMPHOCYTE DEVELOPMENT; MARGINAL ZONE; TRANSCRIPTION FACTORS; HEMATOPOIETIC-CELLS; CD19 FUNCTION; SURVIVAL; MATURE; EXPRESSION; MICE; PATHWAY AB The maintenance of mature B cells hinges on signals emitted from the BAFF-R cell-surface receptor, but the nature of these signals is incompletely understood. Inhibition of canonical NF-kappa B transcription factor activity through ablation of the essential scaffold protein NEW arrests B cell development at the same stage as BAFF-R deficiency. Correspondingly, activation of this pathway by constitutively active I kappa B Kinase2 renders B cell survival independent of BAFF-R:BAFF interactions and prevents proapoptotic PKC8 nuclear translocation. In addition, canonical NF-kappa B activity mediates differentiation and proper localization of follicular and marginal zone B cells in the absence of BAFF-R, but not CD19. By replacing BAFF-R signals, constitutive canonical NF-kappa B signaling, a hallmark of various B cell lymphomas, causes accumulation of resting B cells and promotes their proliferation and survival upon activation, but does not per se induce lymphomagenesis. Therefore, canonical NF-kappa B activity can substitute for BAFF-R signals in B cell development and pathogenesis. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Max Planck Inst Immunbiol, D-79108 Freiburg, Germany. RP Sasaki, Y (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM sasaki@cbr.med.harvard.edu; rajewsky@cbr.med.harvard.edu; supprian@cbr.med.harvard.edu RI Schmidt-Supprian, Marc/F-5893-2011 OI Schmidt-Supprian, Marc/0000-0002-8543-6166 FU NCI NIH HHS [CA92625]; NIAID NIH HHS [AI054636, AI057947] NR 46 TC 189 Z9 194 U1 1 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 2006 VL 24 IS 6 BP 729 EP 739 DI 10.1016/j.immuni.2006.04.005 PG 11 WC Immunology SC Immunology GA 057JN UT WOS:000238592200011 PM 16782029 ER PT J AU Crikis, S Dwyer, K Robson, S Nandurkar, H Cowan, P d'Apice, A AF Crikis, S Dwyer, K Robson, S Nandurkar, H Cowan, P d'Apice, A TI Transgenic expression of CD39 or thrombomodulin confers protection in a murine cardiac xenotransplantation model SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Meeting Abstract CT 24th Annual Scientific Meeting of the Transplantation-Society-of-Australia-and-New-Zealand CY MAR 29-31, 2006 CL Australian Acad Sci, Canberra, AUSTRALIA SP Transplantat Soc Australian & New Zealand HO Australian Acad Sci C1 St Vincents Hosp, Immunol Res Ctr, Melbourne, Vic, Australia. Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JUN PY 2006 VL 84 IS 3 BP A24 EP A24 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 036HU UT WOS:000237063000084 ER PT J AU Crikis, S Dwyer, K Murray-Segal, L Robson, S Cowan, P Durkar, HN d'Apice, A AF Crikis, S Dwyer, K Murray-Segal, L Robson, S Cowan, P Durkar, HN d'Apice, A TI Transgenic CD39 expression protects against renal ischaemia reperfusion injury SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Meeting Abstract CT 24th Annual Scientific Meeting of the Transplantation-Society-of-Australia-and-New-Zealand CY MAR 29-31, 2006 CL Australian Acad Sci, Canberra, AUSTRALIA SP Transplantat Soc Australian & New Zealand HO Australian Acad Sci C1 St Vincents Hosp, Immunol Res Ctr, Melbourne, Vic, Australia. Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JUN PY 2006 VL 84 IS 3 BP A1 EP A1 DI 10.1111/j.1440-1711.2006.01450.x PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 036HU UT WOS:000237063000003 ER PT J AU Siegel, CA Sands, BE AF Siegel, CA Sands, BE TI Risk factors for colorectal cancer in Crohn's colitis: A case-control study SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE Crohn's disease; colitis; colon cancer; risk factors; colonoscopy; surveillance ID PRIMARY SCLEROSING CHOLANGITIS; INFLAMMATORY-BOWEL-DISEASE; CHRONIC ULCERATIVE-COLITIS; SURVEILLANCE COLONOSCOPY; POPULATION; DYSPLASIA; NEOPLASIA; SUPPLEMENTATION; METAANALYSIS; MORTALITY AB Background: Few data exist regarding exposures associated with colorectal cancer (CRC) in patients with Crohn's colitis. The aim of this study was to identify exposures that alter the risk of CRC in patients with Crohn's colitis. Methods: The Research Patient Database Registry at Massachusetts General Hospital was searched to identify cases and controls. Cases had a confirmed diagnosis of Crohn's disease involving at least one third of the colon and a confirmed diagnosis of colorectal adenocarcinoma. Matched controls were randomly chosen from the same Source Population. Paired Univariate analysis was performed to develop an odds ratio (OR) for each exposure. Results: Twenty-seven patients were found to have Crohn's colitis and CRC. Colonoscopy performed for screening or surveillance was associated with an OR of 0.21 (95% CI 0.04-0.77; P = 0.02). Nonsignificant trends for a protective effect included prior appendectomy (OR 0,30; 95% CI 0.05-1.17 P = 0.10) and regular 5-aminosalicylate use (OR 0.30: 95% CI 0.05-1.17; P = 0.10). Smoking history; was associated with a 4-fold-increased risk for CRC. but this was not statistically significant (OR 4.00; 95% CI 0.80-38.67: P = 0.11). Conclusions: We found that having a colonoscopy for an indication of surveillance or screening is associated with decreased risk of CRC in the setting of Crohn's colitis. These data underscore the importance of CRC surveillance for Crohn's colitis in addition to ulcerative colitis and Should prompt further study in this area. C1 Harvard Univ, Massachusetts Gen Hosp, Crohns & Colitis Ctr, Sch Med, Boston, MA 02114 USA. Dartmouth Coll Sch Med, Dartmouth Hitchcock Med Ctr, Sect Gastroenterol & Hepatol, Ctr Inflammatory Bowel Dis, Lebanon, NH USA. RP Sands, BE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Crohns & Colitis Ctr, Sch Med, 165 Camridge St,9th Floor, Boston, MA 02114 USA. EM bsands@partners.org NR 34 TC 34 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD JUN PY 2006 VL 12 IS 6 BP 491 EP 496 DI 10.1097/00054725-200606000-00008 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 050ER UT WOS:000238070800008 PM 16775493 ER PT J AU Ott, MJ Norris, RL Bauer-Wu, SM AF Ott, MJ Norris, RL Bauer-Wu, SM TI Mindfulness meditation for oncology patients: A discussion and critical review SO INTEGRATIVE CANCER THERAPIES LA English DT Review DE cancer; chronic illness; integrative therapies; meditation; mindfulness; Mindfulness-Based Stress Reduction (MBSR) ID STRESS REDUCTION PROGRAM; QUALITY-OF-LIFE; PROSTATE-CANCER OUTPATIENTS; STAGE BREAST-CANCER; ANXIETY DISORDERS; FOLLOW-UP; POSTTRAUMATIC-STRESS; COGNITIVE THERAPY; CLINICAL-TRIAL; INTERVENTION AB The purpose of this article is to (1) provide a comprehensive overview and discussion of mindfulness meditation and its clinical applicability in oncology and (2) report and critically evaluate the existing and emerging research on mindfulness meditation as an intervention for cancer patients. Using relevant keywords, a comprehensive search of MEDLINE, PsycInfo, and Ovid was completed along with a review of published abstracts from the annual conferences sponsored by the Center for Mindfulness in Medicine, Health Care, and Society and the American Psychosocial Oncology Society. Each article and abstract was critiqued and systematically assessed for purpose statement or research questions, study design, sample size, characteristics of subjects, characteristics of mindfulness intervention, outcomes, and results. The search produced 9 research articles published in the past 5 years and 5 conference abstracts published in 2004. Most studies were conducted with breast and prostate cancer patients, and the mindfulness intervention was done in a clinic-based group setting. Consistent benefits-improved psychological functioning, reduction of stress symptoms, enhanced coping and well-being in cancer outpatients-were found. More research in this area is warranted: using randomized, controlled designs, rigorous methods, and different cancer diagnoses and treatment settings; expanding outcomes to include quality of life, physiological, health care use, and health-related outcomes; exploring mediating factors; and discerning dose effects and optimal frequency and length of home practice. Mindfulness meditation has clinically relevant implications to alleviate psychological and physical suffering of persons living with cancer. Use of this behavioral intervention for oncology patients is an area of burgeoning interest to clinicians and researchers. C1 Dana Farber Canc Inst, Nursing & Patient Care Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ott, MJ (reprint author), Dana Farber Canc Inst, Nursing & Patient Care Serv, Boston, MA 02115 USA. EM maryjane_ott@dfci.harvard.edu NR 53 TC 79 Z9 82 U1 4 U2 31 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-7354 J9 INTEGR CANCER THER JI Integr. Cancer Ther. PD JUN PY 2006 VL 5 IS 2 BP 98 EP 108 DI 10.1177/1534735406288083 PG 11 WC Oncology; Integrative & Complementary Medicine SC Oncology; Integrative & Complementary Medicine GA 045UX UT WOS:000237769100002 PM 16685074 ER PT J AU Berra, L Curto, F Bassi, GL Laquerriere, P Baccarelli, A Kolobow, T AF Berra, L Curto, F Bassi, GL Laquerriere, P Baccarelli, A Kolobow, T TI Antibacterial-coated tracheal tubes cleaned with the Mucus Shaver SO INTENSIVE CARE MEDICINE LA English DT Article DE endotracheal tube; tracheal tube suctioning; bactericidal agents; Mucus Shaver; mechanical ventilation; bacterial biofilm ID MECHANICALLY VENTILATED PATIENTS; ENDOTRACHEAL-TUBE; BACTERIAL-COLONIZATION; BIOFILM; WORK AB To assess the long-term benefit from antibacterial coatings of the tracheal tube (ETT), and to keep clean the lumen of the ETT. Experimental animal study. USA National Institutes of Health. Twelve sheep. Twelve ETTs were internally dip-coated with a silver-sulfadiazine in polyurethane. We developed a concentric inflatable silicone rubber "razor", the Mucus Shaver (MS), to shave the ETT lumen free of mucus. In a single pass, we cleaned all mucus from the internal surface of the ETT. Control group: Five intubated sheep were mechanically ventilated for 72h. The ETT was suctioned every 6h. Study group: Six sheep were intubated and mechanically ventilated for 72h. The ETT was suctioned and cleaned with the MS every 6h. An additional sheep was intubated and mechanically ventilated for 168h. Bacteriologic studies and scanning electron microscopy were performed to assess bacterial colonization and thickness of secretions on the internal surface of the ETT. In the control group, the ETT was always heavily colonized: median debris thickness was 380 mu m, range 270-550 mu m. In the study group, there was no colonization and no secretions in the ETT, except for three ETT that were colonized solely at the very tip. Silver-based coating of ETT cleaned with the MS every 6 h significantly reduces accumulation of mucus/secretion and bacterial growth within the ETT following 72h of mechanical ventilation. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NIH, Sect Pulm & Cardiac Assist Devices, Pulm Crit Care Med Branch, Dept Hlth & Human Serv, Bethesda, MD USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Dept Hlth & Human Serv, Bethesda, MD USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Berra, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. EM lberra@partners.org RI Laquerriere, Patrice/P-1025-2016 OI Laquerriere, Patrice/0000-0001-7637-9094 NR 15 TC 43 Z9 43 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD JUN PY 2006 VL 32 IS 6 BP 888 EP 893 DI 10.1007/s00134-006-0125-6 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 044KJ UT WOS:000237670900012 PM 16601964 ER PT J AU Figueiredo, JL Alencar, H Weissleder, R Mahmood, U AF Figueiredo, JL Alencar, H Weissleder, R Mahmood, U TI Near infrared thoracoscopy of tumoral protease activity for improved detection of peripheral lung cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE lung adenocarcinoma; thoracoscopy; VATS; optical probes; near infrared fluorescence imaging ID PROGNOSTIC-SIGNIFICANCE; PULMONARY NODULES; GENE-EXPRESSION; ENZYME-ACTIVITY; CATHEPSIN-B; MICE; FEASIBILITY; SURGERY; CARCINOMA; ARTHRITIS AB Improvement in tumor detection using "smart" probes in combination with microcatheter fluorescence thoracoscopy was evaluated in a mouse model. These imaging probes increase in fluorescence intensity after protease activation; cathepsin B is a major activator of the probes used in this study. Lewis lung carcinoma cells were orthotopically implanted in the subpleural lung parenchyma. Two activatable near infrared (NIR) probes with different excitation and emission wavelength were administered intravenously to determine whether wavelength would modulate target to background ratio (TBR). Mice were selectively intubated and thoracoscopy performed. A 0.8 mm outer diameter imaging catheter was used to record simultaneous white-light (anatomic) and NIR (protease expression) images. At both wavelength pairs evaluated (680/700 and 750/780 nm excitation/emission), the intrinsic luminosity differences between tumors and normal lung in uninjected animals was low (p > 0.3 and p = 0.4, respectively and TBR near 1). In mice receiving protease probes IV, tumors were significantly more fluorescent than adjacent lung (p < 0.0005 for 680/700 and p < 0.006 for 750/780) and TBR increased to approximately 9-fold. Confirmatory fluorescence microscopy and immunohistochemistry were similar and revealed that normal lung had very low levels when compared to tumors of cathepsin B and probe fluorescence. In conclusion, protease sensitive imaging probes selective for cathepsin B, imaged with NIR microcatheters, significantly increase the TBR, making small peripheral lung tumors more readily apparent. Such an approach may be a useful adjunct in staging or restaging patients with lung cancer to find minimal disease in the pleural and subpleural space. (c) 2005 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St 5408, Charlestown, MA 02129 USA. EM mahmood@helix.mgh.harvard.edu FU NCI NIH HHS [P50-CA086355, R24-CA92782]; NIBIB NIH HHS [EB001872] NR 29 TC 36 Z9 36 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 2006 VL 118 IS 11 BP 2672 EP 2677 DI 10.1002/ijc.21713 PG 6 WC Oncology SC Oncology GA 035VH UT WOS:000237029300005 PM 16380983 ER PT J AU Medarova, Z Pham, W Kim, Y Dai, GP Moore, A AF Medarova, Z Pham, W Kim, Y Dai, GP Moore, A TI In vivo imaging of tumor response to therapy using a dual-modality imaging strategy SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE underglycosylated mucin-1; chemotherapy; magnetic resonance imaging; optical imaging; targeted probe ID PANCREATIC-CANCER; NEOADJUVANT CHEMOTHERAPY; ORTHOTOPIC MODEL; NUDE-MICE; CARCINOMA; ANTIGEN; MUCIN; MRI AB In vivo assessment of the outcome of cancer therapy is hampered by the paucity of imaging probes that target tumors specifically and noninvasively. The importance of such probes increases with the continuous development of chemotherapeutics and the necessity to evaluate their effectiveness in a clinical setting. We have recently reported on a dual-modality imaging probe specifically targeting the underglycosylated mucin-1 tumor-specific antigen (uMUC-1), which is one of the early hallmarks of tumorigenesis in a wide variety of tumors. This probe consists of crosslinked superparamagnetic iron oxide nanoparticles (CLIO) for MR imaging, modified with Cy5.5 dye (for near infrared optical fluorescence imaging (NIRF)), and has peptides (EPPT), specifically recognizing uMUC-1, attached to the nanoparticle's dextran coat. In the present study, we demonstrated that this probe could not only detect orthotopically implanted preclinical models of adenocarcinomas but could also track tumor response to chemotherapy in vivo in real time. Considering the high cost associated with the development and testing of new cancer therapeutics and the need for accurate, noninvasive assessment of their effectiveness, we believe that the developed probe represents a valuable research tool relevant to clinical discovery. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol,Mol Imaging La, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol,Mol Imaging La, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu FU NIBIB NIH HHS [EB001727] NR 28 TC 84 Z9 91 U1 1 U2 17 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 2006 VL 118 IS 11 BP 2796 EP 2802 DI 10.1002/ijc.21672 PG 7 WC Oncology SC Oncology GA 035VH UT WOS:000237029300021 PM 16385568 ER PT J AU Vosburgh, KG Stylopoulos, N Thompson, CC Ellis, RE Samset, E Estepar, RS AF Vosburgh, Kirby G. Stylopoulos, Nicholas Thompson, Christopher C. Ellis, Randy E. Samset, Eigil Estepar, Raul San Jose TI Novel real time tracking interface improves the use of laparoscopic and endoscopic ultrasound in the abdomen SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Laparoscopy; Endoscopy; Ultrasound; Computer assisted surgery; Real time tracking; Image guidance AB Endoscopic and laparoscopic ultrasound are imaging modalities often used in diagnosis, biopsy guidance, and interventional procedures in the torso Our Image Registered Laparoscopic (Gastroscopic) UltraSound (IRLUS or IRGUS) systems provide contextual information that complements and reinforces both the positioning of the ultrasound probe and the identification of features in ultrasound images, thereby assisting the clinician in establishing and understanding the primary ultrasound image. Pre-procedure CT and ultrasonic probe tracking are used to create synthetic displays based on the position of the probe tip; these are implemented in real time using recent advances in miniaturized position tracking technology. From a series of experiments in a porcine model, we have established that simple real-time tracking with occasional image translation corrections sufficed to give a clinically useful display of comparison images for feature identification and confirmation in laparoscopic and endoscopic ultrasound systems. The combination of global orientation in a sparse 3D model and direct comparison with an oblique slice of 3D data, which corresponded to the ultrasound image, provided an easily learned and effective environment to assist probe positioning and image interpretation. The system provided greater benefits to the clinician in improving the operator kinematics characteristics for laparoscopic over those provided for endoscopic ultrasound. It is anticipated that these systems will find utility in many diagnostic and therapeutic procedures. C1 [Vosburgh, Kirby G.] CIMIT, Cambridge, MA 02141 USA. [Vosburgh, Kirby G.; Stylopoulos, Nicholas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vosburgh, Kirby G.; Thompson, Christopher C.; Ellis, Randy E.; Samset, Eigil] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Vosburgh, KG (reprint author), CIMIT, Cambridge, MA 02141 USA. NR 15 TC 4 Z9 4 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 2006 VL 1 SU 1 BP 282 EP 284 PG 3 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32YQ UT WOS:000208986900132 ER PT J AU Cai, WL Zalis, M Nappi, J Harris, G Yoshida, H AF Cai, Wenli Zalis, Michael Nappi, Janne Harris, Gordon Yoshida, Hiroyuki TI Structure-based digital bowel cleansing for computer-aided detection of polyps in CT colonography SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Computer-aided detection; CT colonography; Electronic cleansing AB Digital bowel cleansing (DBC) is an emerging method for segmentation of fecal materials, which are tagged by an X-ray-opaque oral contrast agent in CT colonography (CTC) images, effectively removing them for digitally cleansing the colon We developed a novel DBC method that preserves the soft-tissue structures submerged in or partially covered by tagged fecal materials. In our approach, submerged soft-tissue structures are characterized by their local shape signatures that are calculated based on the eigenvalues of a Hessian matrix. A structure-enhancement function is formulated for enhancement of the soft-tissue structures, and the values of the function are integrated into the speed function of a level set method for delineation of the submerged soft-tissue structures while removing the tagged fecal materials. The colon phantom study and the manually cleansed study of ten submerged polyps demonstrated that our new DBC method was shown to delineate polyps better than was possible with our previously reported cleansing method. Application of our computer-aided detection (CAD) scheme showed that the use of the new DBC method substantially reduced the number of false-positive detections compared with those of our previous, thresholding-based method. C1 [Cai, Wenli] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 2 Z9 2 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 2006 VL 1 SU 1 BP 369 EP 371 PG 3 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32YQ UT WOS:000208986900174 ER PT J AU Nappi, J Yoshida, H AF Naeppi, J. Yoshida, H. TI Adaptive normalization of fecal-tagging CT colonography images for computer-aided detection of polyps SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Computer-aided detection; Fecal tagging; Oral contrast; Polyp detection; CT colonography; Virtual colonoscopy AB In fecal-tagging CT colonography, high-density tagging agents artificially elevate observed CT attenuation values of soft-tissue materials We developed an adaptive normalization method which minimizes the effects of this pseudo-enhancement for the purpose of the effective application of computer-aided detection (CAD) in fecal-tagging cases. We evaluated the effect of the normalization method on the performance of our CAD scheme by use of 26 untagged and 20 fecal-tagging polyp cases with supine and prone scans. The results indicated significant improvements in the sensitivity and specificity of the automated detection of polyps 6 mm and larger with the normalization method. C1 [Naeppi, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nappi, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 3 Z9 3 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 2006 VL 1 SU 1 BP 371 EP 372 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32YQ UT WOS:000208986900175 ER PT J AU Cai, W Harris, G Yoshida, H AF Cai, W. Harris, G. Yoshida, H. TI Computer-aided volumetrics of liver tumors in hepatic CT images SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Computer-aided detection; Liver tumor segmentation; Liver segmentation AB Measurement of the volume of focal liver tumors, called liver tumor volumetrics, is indispensable for assessing the growth of tumors and for monitoring the response of tumors to oncology treatment Efficient and accurate detection and segmentation of a liver tumor are essential steps for tumor volumetrics. In this study, we developed a novel computerized method for volumetric segmentation, called a dynamic-threshold level set method, which dynamically shifts a histogram threshold level to drive a propagating shell toward the boundary of a liver tumor. Based on this dynamic-threshold level set method, we developed a three-stage volumetric segmentation scheme for liver tumors: (1) segmentation of the liver, (2) detection of tumors in the segmented liver, and (3) segmentation and measurement of the volume of the detected liver tumors. Fifteen biopsy-confirmed metastases and hemangiomas in seven hepatic CT cases were manually segmented, and the results were compared with those obtained by the computerized scheme. The two volume measurements were highly correlated. Our preliminary result showed that our scheme was effective and accurate in estimating the volume of the liver tumors detected in hepatic CT images. C1 [Cai, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cai, W (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 15 TC 0 Z9 0 U1 3 U2 3 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 2006 VL 1 SU 1 BP 375 EP 377 PG 3 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32YQ UT WOS:000208986900177 ER PT J AU McMurtray, AM Ringman, J Chao, SZ Licht, E Saul, RE Mendez, MF AF McMurtray, Aaron M. Ringman, John Chao, Steven Z. Licht, Eliot Saul, Ronald E. Mendez, Mario F. TI Family history of dementia in early-onset versus very late-onset Alzheimer's disease SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID RISK C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Stanford Univ Hosp, Dept Neurol, Los Angeles, CA USA. RP McMurtray, AM (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit, 691-116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM amcmurtray@mednet.ucla.edu NR 5 TC 9 Z9 9 U1 1 U2 2 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 2006 VL 21 IS 6 BP 597 EP 598 DI 10.1002/gps.1540 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 063PE UT WOS:000239031100013 PM 16783800 ER PT J AU Minnai, GP Tondo, L Salis, P Ghiani, C Manfredi, A Paluello, MM Baethge, C Baldessarini, RJ AF Minnai, GP Tondo, L Salis, P Ghiani, C Manfredi, A Paluello, MM Baethge, C Baldessarini, RJ CA Int Consortium Bipola Disorders Re TI Secular trends in first hospitalizations for major mood disorders with comorbid substance use SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE bipolar disorder; hospitalization; substance use disorder ID BIPOLAR DISORDER; DRUG-ABUSE; MENTAL-DISORDERS; MANIA; ONSET; SCHIZOPHRENIA; DEPRESSION; PSYCHOSIS; ALCOHOL; ILLNESS AB In the past half-century, the incidence of major mood disorders reportedly has risen, and onset age, diminished. Substance-use disorders (SUDs) are commonly comorbid with mood disorders and may influence their course and outcome. Since secular relationships of these disorders remain unknown, we evaluated medical records of 421 patients (233 men, 188 women) at first-lifetime admissions for major depression, mania or mixed bipolar episodes at a public hospital in Italy during 1978-2002, updated diagnoses to DSM-IV criteria, and compared selected factors between subjects with vs. without SUDs, seeking evidence of secular trends in SUDs in association with early mood disorders. SUD was diagnosed in 122 patients (29.0%). SUD risk was greatest in young males. Relative risk (RR) of diagnostic association with SUDs ranked: mixed states (RR 1.80), mania (RR 1.06), depression (RR 0.55). Annual rates of comorbid SUD and mood disorders increased continuously over the 25-yr epoch for all substances (r = 0.640, p < 0.001). Age at onset of illness and at first hospitalization (averaging 36 yr and 38 yr) were unrelated to year of hospitalization in this relatively brief sampling, but patients with SUD were younger at onset and admission, overall. Clinical Global Impression (CGI) ratings of illness severity at hospitalization and discharge were stable across years. These findings indicate a secular increase of comorbid SUD among first admissions for mood disorder, especially in young males, with a parallel increase in the proportion of bipolar disorder diagnoses over the past quarter of a century. C1 San Martino Hosp, Dept Psychiat, Oristano, Sardinia, Italy. Harvard Univ, Sch Med, Dept Psychiat & Neurosci Program, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Biopolar & Psychot Disorders Program, Belmont, MA USA. Massachusetts Gen Hosp, McLean Div, Psychopharmacol Program, Belmont, MA USA. Univ Cagliari, Dept Psychol, Cagliari, Italy. Lucio Bini Mood Disorders Ctr, Cagliari, Italy. RP Tondo, L (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM ltondo@mclean.harvard.edu NR 42 TC 14 Z9 14 U1 4 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD JUN PY 2006 VL 9 IS 3 BP 319 EP 326 DI 10.1017/S1461145705005948 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 052PA UT WOS:000238244400007 PM 16316480 ER PT J AU Evans, AK Rahbar, R Rogers, GF Mulliken, JB Volk, MS AF Evans, AK Rahbar, R Rogers, GF Mulliken, JB Volk, MS TI Robin sequence: A retrospective review of 115 patients SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Review DE Pierre Robin syndrome; tracheotomy; airway obstruction; cleft palate ID UPPER AIRWAY-OBSTRUCTION; MANDIBULAR DISTRACTION OSTEOGENESIS; LARYNGEAL MASK AIRWAY; TONGUE-LIP ADHESION; ROBIN,PIERRE SEQUENCE; PEDIATRIC TRACHEOSTOMIES; STICKLER-SYNDROME; MANAGEMENT; COMPLICATIONS; EXPERIENCE AB Objectives: Review a large series of patients with Robin sequence to document the incidence of (1) associated syndromic diagnoses; (2) co-morbid conditions; (3) frequency and type of operative management for airway compromise and feeding difficulties; and (4) possible differences in treatment between syndromic and non-syndromic infants. Methods: Retrospective case-review of 115 patients with Robin sequence managed between 1962 and 2002 at two tertiary-care teaching hospitals for evaluation of demographic information, clinical findings, and treatment interventions. Results: Fifty-four percent (N = 63) of patients were nonsyndromic. Syndromic patients included: Stickler syndrome (18%), velocardiofacial syndrome (N), Treacher-Collins (5%), facial and hemifacial microsomia (3%), and other defined (3.5%) and undefined (9%) disorders. There was no statistical difference between the syndromic and nonsyndromic patients with regard to need for operative airway management (Fisher's exact test, p = 0.264). Forty-two percent of patients required a feeding gastrostomy tube to correct feeding difficulties. Patients with a syndromic diagnosis were more likely to be developmentally delayed. Fifty-one (44%) patients underwent operative airway management: 61% underwent tongue-lip adhesion and 39% underwent tracheotomy. Fifteen percent of patients initially had tongue-tip adhesion subsequently required tracheotomy. While the preferred treatment for respiratory compromise differed between the two institutions, the percentage of patients requiring operative intervention was similar. Conclusions: The pathogenesis of Robin sequence is multifactorial and syndromic in nearly half of the patients. Operative treatment of respiratory failure was required in 44% of infants; the rate was similar in both hospitals. The operative approach differed significantly between the institutions, however, based on the philosophy and training of the managing surgical specialty. Co-morbid factors such as baseline cardiopulmonary and neurologic status did not play a significant role in surgical decision making. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Childrens Hosp Boston, Dept Otolaryngol, Boston, MA 02115 USA. Childrens Hosp Boston, Div Plast Surg, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Volk, MS (reprint author), Childrens Hosp Boston, Dept Otolaryngol, 300 Longwood Ave, Boston, MA 02115 USA. EM adele.evans@comcast.net; reza.rahbar@childrens.harvard.edu; gary.rogers@childrens.harvard.edu; john.mulliken@childrens.harvard.edu; mark.volk@childrens.harvard.edu OI Volk, Mark/0000-0001-5708-5808 NR 50 TC 99 Z9 103 U1 3 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD JUN PY 2006 VL 70 IS 6 BP 973 EP 980 DI 10.1016/j.ijporl.2005.10.016 PG 8 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 047FB UT WOS:000237864100003 PM 16443284 ER PT J AU Suit, H Loeffler, J Chen, G AF Suit, H Loeffler, J Chen, G TI Chiu-Chen Wang, MD SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Biographical-Item C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Suit, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Founders 544, Boston, MA 02114 USA. EM hsuit@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2006 VL 65 IS 2 BP 317 EP 318 DI 10.1016/j.ijrobp.2006.01.046 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 042QN UT WOS:000237543800001 ER PT J AU Kozak, KR Doppke, KP Katz, A Taghian, AG AF Kozak, KR Doppke, KP Katz, A Taghian, AG TI Dosimetric comparison of two different three-dimensional conformal external beam accelerated partial breast irradiation techniques SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol DE breast cancer; partial breast irradiation; 3D-conformal; external beam; comparison ID VOLUME HISTOGRAM ANALYSIS; NO BOOST TRIAL; CONSERVING SURGERY; RADIATION-THERAPY; EORTC BOOST; STAGE-I; TRAVEL DISTANCE; CANCER; RADIOTHERAPY; MORTALITY AB Purpose: We compare the dosimetry of two techniques for three-dimensional, conformal, external beam, accelerated partial breast irradiation (3D-CPBI) in the supine position. Methods and Materials: Sixteen patients with Stage I breast cancer had PBI treatment plans generated using the multiple, noncoplanar photon field technique and the three-field, mixed-modality technique. Planning target volumes (PTVs; lumpectomy site plus 1.5-2.0 cm margin) and total dose (32 Gy) were held constant to facilitate dosimetric comparisons. Plans were optimized for conformality and PTV coverage. Results: Mixed-modality plans employed fewer fields than multiple, noncoplanar photon field plans (mean 3.2 vs. 4.1). Both techniques provided comparable PTV coverage and in all cases, 95% of the PTV received 90% of the prescribed dose. Volumes of ipsilateral breast receiving greater than 16 Gy were similar; however, the mean volume of ipsilateral breast receiving 8 Gy was significantly lower for mixed-modality plans (58% vs. 66%). No differences in the volumes of ipsilateral lung or heart receiving greater than 5 Gy were observed, however, the mixed-modality technique delivered 2.5 Gy to larger volumes of these organs. Conclusions: Both techniques for supine position, 3D-CPBI provides excellent normal tissue sparing with adequat PTV coverage. The multiple, noncoplanar photon field technique exposes smaller volumes of ipsilateral lung and heart to low dose radiation at the expense of increased plan complexity and larger irradiated breast volumes. (c) 2006 Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX 3, Boston, MA 02114 USA. EM ataghian@partners.org FU NCI NIH HHS [P50 CA89393] NR 25 TC 26 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2006 VL 65 IS 2 BP 340 EP 346 DI 10.1016/j.ijrobp.2005.12.053 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 042QN UT WOS:000237543800006 PM 16690427 ER PT J AU Matsubara, A Nakazawa, T Husain, D Iliaki, E Connolly, E Michaud, NA Gragoudas, ES Miller, JW AF Matsubara, A Nakazawa, T Husain, D Iliaki, E Connolly, E Michaud, NA Gragoudas, ES Miller, JW TI Investigating the effect of ciliary body photodynamic therapy in a glaucoma mouse model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HUMAN ENDOTHELIAL-CELLS; TRANSSCLERAL CYCLOPHOTOCOAGULATION; VISUAL IMPAIRMENT; LASER; BENZOPORPHYRIN; RABBITS; MICE; NEODYMIUM; CYCLOCOAGULATION; INJURY AB PURPOSE. To investigate the morphologic and functional effects of verteporfin ciliary body photodynamic therapy (PDT) in a murine glaucoma model and normal mouse eyes. METHODS. A glaucomatous mouse strain, DBA/2J and a normal control mouse strain (C57BL/6) were used in the study. Vert porfin was injected intravenously at doses of 1.0 (DBA/2J) or 2.0 or 4.0 (C57BL/6) mg/kg. Transscleral irradiation of the ciliary body was performed with light at a wavelength of 689 nm delivered through an optical fiber, with irradiance of 1800 mW/cm(2) and fluence of 100 J/cm(2). Laser irradiation was applied for 360 degrees of the corneoscleral limbus in C57BL/6 normal mice and for 180 degrees in DBA/2J mice. Retreatment was performed in C57BL/6 normal mice that had been treated with 2.0 mg/kg of verteporfin at post-PDT day 7. One eye of each animal was treated, and the fellow eye served as the control. The morphologic effect of PDT on the ocular structures was assessed by light and electron microscopy. The IOP was measured using an applanation tonometer with a fiber-optic pressure sensor. Surviving retinal ganglion cells (RGCs) in DBA/2J mice eyes were retrogradely labeled with a neurotracer dye at 12 weeks after PDT. RESULTS. In all groups, almost all ciliary body blood vessels in the treated area were thrombosed 1 day after PDT. In DBA/2J mice, ciliary epithelium and stroma were severely damaged 1 day after PDT. The mean IOP in treated eyes was significantly reduced compared with that in the control eyes in all groups. The reduction of mean IOP in DBA/2J mouse eyes persisted for 7 weeks, although the mean IOP in normal mouse eyes treated with 2 or 4.0 mg/kg verteporfin returned to the level of the fellow control eyes by 7 and 17 days after treatment, respectively. The mean number of RGCs in the DBA/2J treated eyes was significantly higher than in control eyes. CONCLUSIONS. Ciliary body PDT resulted in morphologic changes in the ciliary body, significant reduction of IOP, and prevention of ganglion cell loss in a mouse glaucoma model. These results suggest that ciliary body PDT is a more selective cyclodestructive technique with potential clinical application in the treatment of glaucoma. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv,Angiogenesis & Laser, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Ophthalmol, Retina Serv, Boston, MA 02118 USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv,Angiogenesis & Laser, 243 Charles St, Boston, MA 02114 USA. EM joan_miller@meei.harvard.edu FU NEI NIH HHS [EY014104] NR 39 TC 13 Z9 14 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 2006 VL 47 IS 6 BP 2498 EP 2507 DI 10.1167/iovs.05-0959 PG 10 WC Ophthalmology SC Ophthalmology GA 048LQ UT WOS:000237949000032 PM 16723462 ER PT J AU Hauser, MA Allingham, RR Linkroum, K Wang, J LaRocque-Abramson, K Figueiredo, D Santiago-Turla, C del Bono, EA Haines, JL Pericak-Vance, MA Wiggs, JL AF Hauser, MA Allingham, RR Linkroum, K Wang, J LaRocque-Abramson, K Figueiredo, D Santiago-Turla, C del Bono, EA Haines, JL Pericak-Vance, MA Wiggs, JL TI Distribution of WDR36 DNA sequence variants in patients with primary open-angle glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GENOME-WIDE SCAN; GENE; IDENTIFICATION; REGION; LOCUS; POAG; OPTINEURIN; MAPS AB PURPOSE. To determine the distribution of WDR36 sequence variants in a cohort of patients with primary open-angle glaucoma (POAG) in the United States. METHODS. All of the 23 coding exons and flanking introns of the WDR36 gene were sequenced in 118 probands from families with at least two members affected by POAG, 6 probands from juvenile-onset POAG families, and 108 control individuals. RESULTS. Thirty-two WDK36 sequence variants were found m this population of patients with POAG. Nonsynonymous single-nucleotide polymorphisms (SNPs), including those previously described as "disease-causing" and "disease susceptibility," were found in 17% of POAG patients and 4% of control subjects. Although the distribution of WDR36 variants in the pedigrees did not show consistent segregation with the disease, the WDR36 sequence variants were found more frequently in patients with more severe disease. CONCLUSIONS. The results of this study suggest that abnormalities in WDR36 alone are not sufficient to cause POAG. The association of WDR36 sequence variants with more severe disease in affected individuals suggests that defects in the WDR36 gene can contribute to POAG and that WDR36 may be a glaucoma modifier gene. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Duke Univ, Sch Med, Ctr Human Genet, Durham, NC USA. Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC USA. Vanderbilt Univ, Sch Med, Ctr Human Genet, Nashville, TN 37212 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu RI Haines, Jonathan/C-3374-2012 FU NEI NIH HHS [P30 EY14104, R01 EY13315, R01 EY15543, R01 EY15586] NR 20 TC 83 Z9 90 U1 0 U2 0 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 2006 VL 47 IS 6 BP 2542 EP 2546 DI 10.1167/iovs.05-1476 PG 5 WC Ophthalmology SC Ophthalmology GA 048LQ UT WOS:000237949000038 PM 16723468 ER PT J AU Zambarakji, HJ Nakazawa, T Connolly, E Lane, AM Mallemadugula, S Kaplan, M Michaud, N Hafezi-Moghadam, A Gragoudas, ES Miller, JW AF Zambarakji, HJ Nakazawa, T Connolly, E Lane, AM Mallemadugula, S Kaplan, M Michaud, N Hafezi-Moghadam, A Gragoudas, ES Miller, JW TI Dose-dependent effect of pitavastatin on VEGF and angiogenesis in a mouse model of choroidal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID AGE-RELATED MACULOPATHY; COA REDUCTASE INHIBITOR; ENDOTHELIAL GROWTH-FACTOR; COENZYME-A REDUCTASE; CORONARY-HEART-DISEASE; MACULAR DEGENERATION; STATIN USE; RISK; RATS; PRAVASTATIN AB PURPOSE. To evaluate the relation between statin therapy, vascular endothelial growth factor (VEGF) expression, vascular leakage, and CNV size in experimentally induced choroidal neovascularization (CNV). METHODS. Wild-type (C57 BI/6J) mice received pitavastatin 0.18 mg/kg per day (group 1), 1.8 mg/kg per day (group 2) or 18 mg/kg per day (group 3) for 3 days before laser-induced CNV and continued to receive the drug for 14 days. Serum total cholesterol levels were measured by spectrophotometry. Fluorescein angiograms were graded by masked observers. VEGF protein levels from retinal lysates were measured and CNV area was assessed by histology. RESULTS. Pitavastatin did not reduce total serum cholesterol at any of the doses used. The incidence rate ratios for development of clinically significant CNV leakage was 0.62 (95% CI , 0.46-0.84) for group 1, 0.56 (95% CI, 0.28-1.10) for group 2, and 1.22 (95% CI, 1.01-1.48) for group 3 (P = 0.002, 0.09, and 0.04, respectively). Mean CNV area increased by 13%, 22%, and 95% in groups 1, 2, and 3, respectively (P > 0.05). Normalized VEGF levels did not mirror the observed changes in fluorescein leakage and CNV area in histologic examination. CONCLUSIONS. Pitavastatin therapy for experimental CNV in wild-type mice resulted in reduced fluorescein leakage at a dose of 0.18 mg/kg per day. The higher dose of 18 mg/kg per day resulted in increased fluorescein leakage and a trend toward an increase in CNV size, indicating a potentiating effect in choroidal neovascular disease. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Angiogenesis Lab,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Retina Lab,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Angiogenesis Lab,Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM joan_miller@meei.harvard.edu OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NEI NIH HHS [P30EY14104] NR 49 TC 16 Z9 17 U1 0 U2 2 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 2006 VL 47 IS 6 BP 2623 EP 2631 DI 10.1167/iovs.05-0855 PG 9 WC Ophthalmology SC Ophthalmology GA 048LQ UT WOS:000237949000049 PM 16723479 ER PT J AU Clermont, AC Cahill, M Salti, H Rook, SL Rask-Madsen, C Goddard, L Wong, JS Bursell, D Bursell, SE Aiello, LP AF Clermont, Allen C. Cahill, Mark Salti, Haytham Rook, Susan L. Rask-Madsen, Christian Goddard, Lucy Wong, Jun S. Bursell, Dahlia Bursell, Sven E. Aiello, Lloyd Paul TI Hepatocyte growth factor induces retinal vascular permeability via MAP-kinase and PI-3 kinase without altering retinal hemodynamics SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; NITRIC-OXIDE SYNTHASE; TRANSENDOTHELIAL RESISTANCE TER; SCATTER FACTOR HGF/SF; C-MET; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; IN-VIVO; PARACELLULAR PERMEABILITY; SIGNALING PATHWAY AB PURPOSE. Although vascular endothelial growth factor (VEGF) is a key mediator of retinal vascular permeability (RVP), there may be additional humoral contributors. Hepatocyte growth factor (HGF) induces endothelial cell separation, regulates expression of cell adhesion molecules and is increased in the vitreous fluid of patients with proliferative diabetic retinopathy. The purpose of this study was to evaluate the in vivo effects of HGF on RVP and retinal hemodynamics and delineate the signaling pathways. METHODS. RVP was assessed by vitreous fluorescein fluoropho-tometry in rats. Time course and dose-response were determined after intravitreal HGF injection. MAP kinase (MAPK), phosphatidylinositol 3-kinase (PI-3 kinase), and protein kinase C (PKC) involvement were examined by using selective inhibitors. Retinal blood flow (RBF) and mean circulation time (MCT) were evaluated by video fluorescein angiography. RESULTS. HGF increased RVP in a time- and dose-dependent manner. HGF-induced RVP was evident 5 minutes after injection, and reached maximal levels after. 25 minutes (+ 107% versus vehicle, P = 0.002). This effect was comparable to that of maximum VEGF stimulation (134% +/- 128% at 25 ng/mL). Selective inhibitors of MAPK (PD98059) and PI-3 kinase (LY294002) suppressed HGF-induced RVP by 86% +/- 44% (P = 0.015) and 97% +/- 59% (P = 0.021), respectively. Non-isoform-selective inhibition of PKC did not significantly decrease HGF-induced RVP. Although VEGF increases RBF and reduces MCT, HGF did not affect either. CONCLUSIONS. HGF increases RVP in a time- and dose-dependent manner at physiologically relevant concentrations with a magnitude and profile similar to that of VEGF, without affecting retinal hemodynamics. Thus, HGF may represent another clinically significant contributor to retinal edema distinct from the actions of VEGF. C1 Joslin Diabet Ctr, Sect Eye Res, Boston, MA 02215 USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Duke Univ, Ctr Eye, Durham, NC USA. Amer Univ Beirut, Med Ctr, Dept Ophthalmol, Beirut, Lebanon. Hosp Univ Kebangsaan Malaysia, Dept Ophthalmol, Jalan Yaacob Latiff, Kuala Lumpur, Malaysia. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Sect Eye Res, 1 Joslin Pl, Boston, MA 02215 USA. EM lpaiello@joslin.harvard.edu NR 59 TC 18 Z9 19 U1 0 U2 3 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 2006 VL 47 IS 6 BP 2701 EP 2708 DI 10.1167/iovs.05-0071 PG 8 WC Ophthalmology SC Ophthalmology GA 048LQ UT WOS:000237949000059 PM 16723489 ER PT J AU Williamson, D Brown, E Perlis, RH Ahl, J Baker, RW Tohen, M AF Williamson, D Brown, E Perlis, RH Ahl, J Baker, RW Tohen, M TI Clinical relevance of depressive symptom improvement in bipolar I depressed patients SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE olanzapine; olanzapine-fluoxetine combination; bipolar I depression; factor analysis ID RATING-SCALE; MADRS; SENSITIVITY; VALIDITY AB Background: Gaps remain between rating scale changes obtained in a clinical trial and what those results mean in clinical practice. Objective: To better understand the relevance of results from a clinical trial we examined the relationship between rating scale measures and the clinicians' assessment of illness severity. Methods: Data from a randomized double-blind 8-week study of bipolar I depression were examined post hoc in patients who received placebo (PLA, n = 355), olanzapine (n=351) (OLZ, 5 to 20 mg/d), or olanzapine-fluoxetine combination (n=82) (OFC, 6 and 25, 6 and 50, or 12 and 50 mg/d). Principal components analysis identified related symptoms (factors) from Montgomery-Asberg Depression Rating Scale (MADRS) item scores. Regression analysis examined baseline to endpoint changes in factor scores and Clinical Global Impression (CGI) scores. Mixed-effects model repeated measures analysis assessed differences between treatment groups. Results: MADRS factors identified were: sadness, negative thoughts, detachment, and neurovegetative symptoms. Factor and CGI scores were significantly reduced from baseline to endpoint (LOCF) in the combination therapy group as compared with placebo (p <.01). Changes in factor scores were highly correlated (p <.001) with changes in the CGI. Over 80% of this treatment effect was attributable to indirect effects of improvements in the MADRS factors, the remaining difference could not be explained even when changes in the YMRS and HAMA scores were included in the analytical model. Conclusions: The changes in MADRS factors were closely aligned with the clinician's assessment of overall depression severity, which may suggest a high degree of clinical relevance for differences observed between treatments. (c) 2006 Elsevier B.V. All rights reserved. C1 Eli Lilly & Co, Lilly Technol Ctr, Lilly Res Labs, Indianapolis, IN 46221 USA. Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. RP Williamson, D (reprint author), Eli Lilly & Co, Lilly Technol Ctr, Lilly Res Labs, South,1400 Raymond St, Indianapolis, IN 46221 USA. EM d.williamson@lilly.com OI Ahl, Jonna/0000-0002-5661-6053 NR 12 TC 8 Z9 10 U1 0 U2 3 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 2006 VL 92 IS 2-3 BP 261 EP 266 DI 10.1016/j.jad.2006.02.011 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 050ZS UT WOS:000238130500014 PM 16563521 ER PT J AU Glahn, DC Bearden, CE Bowden, CL Soares, JC AF Glahn, DC Bearden, CE Bowden, CL Soares, JC TI Reduced educational attainment in bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; education; cognitive; socioeconomic status; matching facile; IQ ID SCHIZOPHRENIA AB Objective: To document educational attainment in relation to IQ in patients with bipolar disorder, in order to establish guidelines for matching patients with appropriate comparison subjects. Method: 60 adult patients with bipolar disorder were compared to 60 demographically matched healthy subjects on IQ measures and educational attainment. Results: Despite comparable IQ levels, patients with bipolar disorder completed fewer years of education than controls. Although over 60% of both groups entered college, only 16% of bipolar patients received a college degree. In contrast 47% of the comparison sample completed college. Educational attainment did not differ between subgroups of patients with earlier vs. later illness onset, nor as a function of comorbid substance abuse. Limitations: Other comorbidities, such as anxiety disorders or sub-clinical symptomatology prior to illness onset, were not assessed. Conclusions: Educational attainment is disrupted in bipolar disorder, and thus should not be used for matching patients and comparison subjects. Reduced educational attainment may contribute to later functional disability in this illness. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Glahn, DC (reprint author), Univ Texas, Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr,Mail Code 7792, San Antonio, TX 78229 USA. EM glahn@uthscsa.edu FU NCRR NIH HHS [M01-RR-01346]; NIMH NIH HHS [MH 068662, MH 01736] NR 10 TC 25 Z9 25 U1 0 U2 3 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 2006 VL 92 IS 2-3 BP 309 EP 312 DI 10.1016/j.jad.2006.01.025 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 050ZS UT WOS:000238130500023 PM 16524631 ER PT J AU Bush, RK Peden, DB AF Bush, RK Peden, DB TI Advances in environmental and occupational disorders SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE environment; allergens; asthma; occupational diseases; environmental controls ID AIR-POLLUTION; ALLERGEN AVOIDANCE; MAJOR ALLERGEN; PUBLIC-HEALTH; IN-VIVO; ASTHMA; CHILDREN; IGE; EXPOSURE; ENDOTOXIN AB As with the previous year, 2005 was a very active year for investigation of the effect of environmental agents on allergic disease, be they allergens, pollutants, bioaerosols, or occupationally encountered agents. There were a large number of articles on the prevalence of allergic disease in the United States, identification and characterization of a number of allergens, and the role of indoor allergens and potential mitigation of the effect of such allergens, as well as the hygiene hypothesis, air pollution, and the effect of these agents on airway disease. The Journal of Allergy and Clinical Immunology also saw very interesting case reports and mechanistic studies examining the causes of occupational immune-mediated disease. There were also reports on gene-environment interactions, highlighting the importance of such interactions in modulating the risk for development of allergic disease. That these interactions have proved to be remarkably complex comes as no surprise to the allergy and immunology community because allergists and immunologists have long appreciated the role of environmental influences on disease. C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Sect Allergy Pulm & Crit Care Med, Madison, WI 53706 USA. Univ N Carolina, Sch Med, Div Pediat Immunol & Infect Dis, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC USA. RP Bush, RK (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM Robert.Bush@med.va.gov NR 48 TC 2 Z9 2 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2006 VL 117 IS 6 BP 1367 EP 1373 DI 10.1016/j.jaci.2006.04.009 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 053UX UT WOS:000238332300024 PM 16750999 ER PT J AU Oral, E Christensen, SD Malhi, AS Wannomae, KK Muratoglu, OK AF Oral, E Christensen, SD Malhi, AS Wannomae, KK Muratoglu, OK TI Wear resistance and mechanical properties of highly cross-linked, ultrahigh-molecular weight polyethylene doped with vitamin E SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; highly cross-linked polyethylene; oxidation resistance; fatigue resistance; vitamin E; biomaterials ID TOTAL HIP-REPLACEMENT; ALPHA-TOCOPHEROL; ACETABULAR COMPONENTS; CLINICAL-PERFORMANCE; ANTIOXIDANT ACTIVITY; GAMMA-STERILIZATION; FEMORAL-HEAD; UHMWPE; RADIATION; LUBRICATION AB Our hypothesis was that cross-linked, ultrahigh-molecular weight polyethylene (UHMWPE) stabilized with vitamin E (alpha-tocopherol) would be wear-resistant and fatigue-resistant. Acetabular liners were radiation cross-linked, doped with vitamin E, and-sterilized. Hip simulator wear rate of vitamin E-stabilized UHMWPE was approximately I and 6 mg/million-cycles in clean serum and in serum with third-body particles, respectively, a 4-fold to 10-fold decrease from that of conventional UHMWPE. The ultimate strength, yield strength, elongation at break, and fatigue resistance of vitamin E-stabilized URMWPE were significantly higher than that of 100 kGy-irradiated and melted UHMWPE, and were unaffected by accelerated aging. Rim impingement testing with 3.7-mm-thick acetabular liners up to 2 million-cycles showed no significant damage of the cross-linked liners compared with conventional, gamma-sterilized in inert UHMWPE, vitamin E-stabilized liners. The data indicate good in vitro wear properties and improved mechanical and fatigue properties for vitamin E-stabilized, cross-linked UHMWPE. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR051142, R01 AR051142-02] NR 35 TC 98 Z9 103 U1 3 U2 27 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 2006 VL 21 IS 4 BP 580 EP 591 DI 10.1016/j.arth.2005.07.009 PG 12 WC Orthopedics SC Orthopedics GA 059AH UT WOS:000238705200018 PM 16781413 ER PT J AU Mattos-Graner, RO Porter, KA Smith, DJ Hosogi, Y Duncan, MJ AF Mattos-Graner, Renata O. Porter, Kristen A. Smith, Daniel J. Hosogi, Yumiko Duncan, Margaret J. TI Functional analysis of glucan binding protein B from Streptococcus mutans SO JOURNAL OF BACTERIOLOGY LA English DT Article ID YYCF RESPONSE-REGULATOR; ESCHERICHIA-COLI; CELL-SHAPE; IN-VIVO; BACILLUS-SUBTILIS; SEQUENCE-ANALYSIS; DENTAL-CARIES; PNEUMONIAE R6; GENE; EXPRESSION AB Mutans streptococci are major etiological agents of dental caries, and several of their secreted products contribute to bacterial accumulation on teeth. Of these, Streptococcus mutans glucan binding protein B (GbpB) is a novel, immunologically dominant protein. Its biological function is unclear, although GbpB shares homology with a putative peptidoglycan hydrolase from S. agalactiae and S. pneumoniae, indicative of a role in murein biosynthesis. To determine the cellular function of GbpB, we used several approaches to inactivate the gene, analyze its expression, and identify interacting proteins. None of the transformants analyzed were true gbpB mutants, since they all contained both disrupted and wild-type gene copies, and expression of functional GbpB was always conserved. Thus, the inability to obtain viable gbpB null mutants supports the notion that gbpB is an essential gene. Northern blot and real-time PCR analyses suggested that induction of gbpB expression in response to stress was a strain-dependent phenomenon. Proteins that interacted with GbpB were identified in pull-down and coimmunoprecipitation assays, and these data suggest that GbpB interacts with ribosomal protein L7/L12, possibly as part of a protein complex involved in peptidoglycan synthesis and cell division. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM mduncan@forsyth.org RI Mattos-Graner, Renata/C-9410-2012 OI Mattos-Graner, Renata/0000-0001-8309-8135 FU NIDCR NIH HHS [R37 DE006153, R37 DE 06153] NR 50 TC 33 Z9 36 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 2006 VL 188 IS 11 BP 3813 EP 3825 DI 10.1128/JB.01845-05 PG 13 WC Microbiology SC Microbiology GA 047PZ UT WOS:000237892500010 PM 16707674 ER PT J AU McCray, AT AF McCray, AT TI Conceptualizing the world: Lessons from history SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article; Proceedings Paper CT International Conference on Biomedical Ontologies CY APR 29-MAY 02, 2005 CL Rome, ITALY SP Int Med Informat Assoc Working Grp 6, European Federat Med Informat, Inst Formal Ontol & Med Informat Sci, European Union Network Excellence Semant Interoperabil, Data Min Biomed DE metaphysics; classification; knowledge representation; semantics; terminology; concept formation; history ID TAXONOMY; NAMES; CLASSIFICATION; CATEGORIES; KNOWLEDGE AB Throughout history, philosophers, scientists, and other scholars have named and organized the salient elements of the world. These efforts have led to conceptualizations that differ widely in both content and form. This paper argues that all conceptualizations are biased, both because they depend on the purposes for which they have been created, and because they are closely tied to the world view of their designers. This bias needs to be recognized, and its consequences need to be addressed if the conceptualizations are to be used for purposes other than those for which they were designed. The paper begins with a brief overview of the disciplines that have been concerned with conceptualizing particular domains. This is followed by a non-exhaustive, illustrative, historical perspective, and the paper concludes with the interesting case study of biological taxonomy. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Ctr Clin Comp, BIDMC, Boston, MA 02215 USA. RP McCray, AT (reprint author), Harvard Univ, Sch Med, Ctr Clin Comp, BIDMC, 330 Brookline Ave, Boston, MA 02215 USA. EM alexa_mccray@hms.harvard.edu NR 51 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD JUN PY 2006 VL 39 IS 3 BP 267 EP 273 DI 10.1016/j.jbi.2005.08.007 PG 7 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 048XS UT WOS:000237980400003 PM 16243005 ER PT J AU Chung, C Mesa, J Randolph, MA Yaremchuk, M Burdick, JA AF Chung, C Mesa, J Randolph, MA Yaremchuk, M Burdick, JA TI Influence of gel properties on neocartilage formation by auricular chondrocytes photoencapsulated in hyaluronic acid networks SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE cartilage; tissue engineering; hyaluronic acid; photopolymerization; hydrogel ID BOVINE ARTICULAR-CARTILAGE; IN-VITRO; REPAIR; ASSAY; COLLAGEN; CULTURES; RABBITS; DNA AB The objective of this study was to determine how changes in the network structure and properties of hyaluronic acid (HA) hydrogels, due to variations in the macromer molecular weight (50-1100 kDa) and macromer concentration (2-20 wt %), affect neocartilage formation by encapsulated auricular chondrocytes. To investigate tissue formation, swine auricular chondrocytes were photoencapsulated in the various networks, implanted subcutaneously in the dorsum of nude mice, and explanted after 6 and 12 weeks for biochemical and histological analysis. After 12 weeks, the various constructs were 81-93% water, contained between 0.1 x 10(6) and 0.6 x 10(6) chondrocytes per sample, and consisted of 0-0.049 mu g chondroitin sulfate/mu g wet weight (glycosaminoglycan (GAG) content) and 0.002-0.060 mu g collagen/mu g wet weight. Histological staining showed an even distribution of chondrocytes and GAGs in addition to minimal type I collagen staining and intense and uniform type 11 collagen staining in the constructs with greatest neocartilage production. Hydrogels fabricated from 2 wt % of the 50 kDa HA macromer most resembled the properties of native cartilage and show the greatest promise for continued development for cartilage regeneration. (c) 2006 Wiley Periodicals, Inc. C1 Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02115 USA. RP Burdick, JA (reprint author), Univ Penn, Dept Bioengn, 120 Hayden Hall,3320 Smith Walk, Philadelphia, PA 19104 USA. EM burdick2@seas.upenn.edu FU NIDCR NIH HHS [K22 DE-015761, K22 DE015761, K22 DE015761-02] NR 29 TC 75 Z9 78 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD JUN 1 PY 2006 VL 77A IS 3 BP 518 EP 525 DI 10.1002/jbm.a.30660 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 041CQ UT WOS:000237431300010 PM 16482551 ER PT J AU Millett, PJ Porramatikul, M Chen, N Zurakowski, D Warner, JJP AF Millett, PJ Porramatikul, M Chen, N Zurakowski, D Warner, JJP TI Analysis of transfusion predictors in shoulder arthroplasty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL HIP-ARTHROPLASTY; PREOPERATIVE AUTOLOGOUS DONATION; BLOOD-TRANSFUSION; KNEE ARTHROPLASTY; UNITED-STATES; SURGERY; RISK; REPLACEMENT; COLLECTION; INFECTION AB Background: We are not aware of any previous study that has examined predictive factors for blood transfusion after shoulder arthroplasty. We analyzed the association between clinical factors and the need for postoperative blood transfusion and documented the use and waste of predonated blood in a group of patients managed with shoulder arthroplasty. Methods: A retrospective study of 119 patients who underwent 124 shoulder arthroplasties (including eighty-seven primary uncomplicated total shoulder arthroplasties, twenty-seven revision or complicated primary total shoulder arthroplasties, and ten hemiarthroplasties) from 2001 to 2004 was performed. Logistic regression analysis was conducted to determine which clinical variables were predictive of transfusion. Results: A postoperative transfusion was received after thirty-one arthroplasties (25%). The strongest predictor of blood transfusion after shoulder arthroplasty was the preoperative hemoglobin level (likelihood ratio test = 37.8, p < 0.0001). Patients with a preoperative hemoglobin level of between 110 and 130 g/L had a five times greater estimated risk of transfusion than those with a level of > 130 g/L (p < 0.001). Gender, body mass index, preoperative diagnosis, comorbid conditions, use of anticoagulants or aspirin, autologous predonation status, type of anesthesia, operative time, and decrease in hemoglobin or hematocrit were not predictors of blood transfusion. One hundred and two (78%) of the 131 predonated autologous units were discarded. Patients with a preoperative hemoglobin level of > 130 g/L had the highest percentage of wasted units (90%; fifty-five of sixty-one). Preoperative autologous blood donation did not eliminate the risk of allogeneic blood transfusion in autologous donors. Conclusions: The preoperative hemoglobin level is the strongest predictor of blood transfusion after shoulder surgery, and individuals with a preoperative hemoglobin level of < 110 g/L have the highest risk of transfusion. On the basis of these findings, we do not recommend autologous predonation for individuals with a preoperative hemoglobin level of > 130 g/L, to avoid unnecessary expense and waste. C1 Brigham & Womens Hosp, Harvard Shoulder Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Millett, PJ (reprint author), Steadman Hawkins Clin, 181 W Meadow Dr, Vail, CO 81657 USA. EM drmillett@steadman-hawkins.com NR 26 TC 22 Z9 23 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 2006 VL 88A IS 6 BP 1223 EP 1230 DI 10.2106/JBJS.E.00706 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 049RY UT WOS:000238035400008 PM 16757754 ER PT J AU Harness, NG Ring, D Zurakowski, D Harris, GJ Jupiter, JB AF Harness, NG Ring, D Zurakowski, D Harris, GJ Jupiter, JB TI The influence of three-dimensional computed tomography reconstructions on the characterization and treatment of distal radial fractures SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ARTICULAR FRACTURES; OBSERVER AGREEMENT; RELIABILITY; END AB Background: Computed tomography identifies important characteristics of distal radial fractures better than plain radiographs do. Our hypothesis was that three-dimensional computed tomography images would further increase the reliability and accuracy of radiographic characterization of distal radial fractures. Methods: Four independent observers evaluated radiographic images of thirty intra-articular fractures of the distal part of the radius for the presence of a fracture line in the coronal plane, impacted central articular fragments, the presence of comminution (defined as more than three articular fragments), and the number of fracture fragments. A treatment was selected on the basis of the interpretation of the radiographic studies. Three rounds of evaluation were compared: (1) radiographs and two-dimensional computed tomography, (2) radiographs and three-dimensional computed tomography two weeks later, and (3) all three types of images two weeks after that. This cycle was then repeated to assess intraobserver reliability. Results: Three-dimensional computed tomography improved the intraobserver agreement, but not the interobserver agreement, regarding the presence of coronal plane fracture lines and central articular fragment depression. Three-dimensional computed tomography improved both the intraobserver and the interobserver agreement regarding the presence of articular comminution. Interobserver agreement increased when three-dimensional computed tomography was used to determine the exact number of articular fracture fragments. The sensitivity and accuracy of identifying specific fracture characteristics (as compared with intraoperative findings) improved when three-dimensional imaging was used in conjunction with two-dimensional imaging as compared with two-dimensional imaging alone. The addition of three-dimensional computed tomography to two-dimensional computed tomography influenced treatment recommendations, resulting in a significantly greater number of decisions for an open approach (p < 0.05) and combined dorsal and volar exposure (p < 0.001). Conclusions: Three-dimensional computed tomography improves both the reliability and the accuracy of radiographic characterization of articular fractures of the distal part of the radius and influences treatment decisions. Future studies will be required to determine the impact of these decisions on patient outcome. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. RP Harness, NG (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 20 TC 51 Z9 58 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 2006 VL 88A IS 6 BP 1315 EP 1323 DI 10.2106/JBJS.E.00686 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 049RY UT WOS:000238035400020 PM 16757766 ER PT J AU Bosse, MJ Henley, B Bray, T Vrahas, MS AF Bosse, MJ Henley, B Bray, T Vrahas, MS TI An AOA critical issue - Access to emergent musculoskeletal care: Resuscitating orthopaedic emergency-department coverage SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TRAUMA; SURGERY; FUTURE C1 Carolinas Med Ctr, Dept Orthopaed Surg, Charlotte, NC 28232 USA. Univ Washington, Sch Med, Harborview Med Ctr, Dept Orthopaed Surg & Sports Med, Seattle, WA 98104 USA. Reno Orthopaed Clin, Reno, NV 89503 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bosse, MJ (reprint author), Carolinas Med Ctr, Dept Orthopaed Surg, POB 32861, Charlotte, NC 28232 USA. EM mbosse@carolinas.org NR 24 TC 16 Z9 16 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 2006 VL 88A IS 6 BP 1385 EP 1394 DI 10.2106/JBJS.E.01230 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 049RY UT WOS:000238035400031 PM 16757775 ER PT J AU Conard, MW Heidenreich, P Rumsfeld, JS Weintraub, WS Spertus, J AF Conard, MW Heidenreich, P Rumsfeld, JS Weintraub, WS Spertus, J CA Cardiovascular Outcomes Res Consor TI Patient-reported economic burden and the health status of heart failure patients SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE difficulty affording health care; cardiovascular disease ID CASE-FINDING INSTRUMENTS; HIGH-RISK PATIENTS; MYOCARDIAL-INFARCTION; SOCIOECONOMIC-STATUS; CARE; DEPRESSION; COSTS; READMISSION AB Background: Heart failure (HF) guidelines recommend treatment with multiple medications to improve survival, functioning, and quality of life. Yet, HF treatments can be costly, resulting in significant economic burden for some patients. To date, there are few data on the impact of patients' perceived difficulties in affording medical care on their health outcomes. Methods and Results: Comprehensive clinical data, health status, and the perceived economic burden of 539 HF outpatients from 13 centers were assessed at baseline and 1 year later. Health status was quantified with the Kansas City Cardiomyopathy Questionnaire overall summary score. Cross-sectional and longitudinal (1-year) analyses were conducted comparing the health status of patients with and without self-reported economic burden. Patients with economic burden had significantly lower health status scores at both baseline and 1 year later. Although baseline perceptions of economic burden were associated with poorer health status, patients' perceived difficulty affording medical care at 1 year was a more important determinant of lower 1-year health status. Conclusion: HF patients reporting difficulty affording their medical care had lower perceived health status than those reporting little to no economic burden. More research is needed to further evaluate this association and to determine whether addressing perceived economic difficulties affording health care can improve HF patients' health status. C1 Univ Missouri, Kansas City & Midamer Heart Inst, St Lukes Hosp, Kansas City, MO 64110 USA. Denver VA Med Ctr, Denver, CO USA. Palo Alto VA Med Ctr, Palo Alto, CA USA. Emory Univ, Atlanta, GA 30322 USA. RP Conard, MW (reprint author), St James Hosp, 20201 S Crawford Ave, Olympia Fields, IL 60461 USA. OI Heidenreich, Paul/0000-0001-7730-8490 NR 31 TC 13 Z9 13 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD JUN PY 2006 VL 12 IS 5 BP 369 EP 374 DI 10.1016/j.cardfail.2006.03.004 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 056JK UT WOS:000238518600009 PM 16762800 ER PT J AU Arzola-Castaner, D Taub, C Heist, EK Fan, DL Haelewyn, K Mela, T Picard, MH Ruskin, JN Singh, JP AF Arzola-Castaner, D Taub, C Heist, EK Fan, DL Haelewyn, K Mela, T Picard, MH Ruskin, JN Singh, JP TI Left ventricular lead proximity to an akinetic segment and impact on outcome of cardiac resynchronization therapy SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE cardiac resynchronization therapy; hemodynamic response; heart failure; cardiac pacing ID CONGESTIVE-HEART-FAILURE; ECHOCARDIOGRAPHIC EVALUATION; SITE AB Background: Previous studies report that the optimal pacing site for cardiac resynchronization therapy (CRT) is along the left ventricular (LV) lateral and postero-lateral (PL) wall. However, little is known regarding whether pacing over an akinetic site impacts the contractile response and long-term outcome from CRT. Methods and Results: A total of 38 patients with ischemic cardiomyopathy were studied for their acute hemodynamic and 12-month clinical response to CRT. The intraindividual percentage change in dP/dt (%Delta dP/dt), over baseline, was derived from the mitral regurgitation (MR) Doppler profile with CRT on versus off. Two-dimensional echocardiography was used for myocardial segmentation and determinination of akinetic sites. LV lead implant site was determined using angiographic and radiographic data and categorized as being "on" (group 1) or "off" (group 2) an akinetic site. Long-term response was measured as a combined endpoint of hospitalization for heart failure and/or all cause mortality at 12 months. Time to primary endpoint was estimated by the Kaplan-Meier method. Clinical characteristics and acute hemodynamic response was similar in both (group 1 [n = 14]; %Delta dP/dt 48.8 +/- 67.4% vs group 2 [n = 24]; %Delta dP/dt 32.2 +/- 40.1%, P = 0.92). No difference in long-term outcome was observed (P = 0.59). In contrast, lead placement in PL or mid-lateral (ML) positions was associated with a better acute hemodynamic response when compared to antero-lateral (AL) positions (PL, %Delta dP/dt 45.7 +/- 50.7% and ML, %Delta dP/dt 45.1 +/- 58.8% vs AL, %Delta dP/dt 2.9 +/- 30.9%, respectively, P = 0.014). Conclusion: LV lead proximity to an akinetic segment does not impact acute hemodynamic or 12-month clinical response to CRT. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv,Cardiac Ultrasound Lab, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 20 TC 14 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUN PY 2006 VL 17 IS 6 BP 623 EP 627 DI 10.1111/j.1540-8167.2006.00480.x PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 045KC UT WOS:000237740000011 PM 16836711 ER PT J AU Bhasin, S Cunningham, GR Hayes, FJ Matsumoto, AM Snyder, PJ Swerdloff, RS Montori, VM AF Bhasin, Shalender Cunningham, Glenn R. Hayes, Frances J. Matsumoto, Alvin M. Snyder, Peter J. Swerdloff, Ronald S. Montori, Victor M. TI Testosterone therapy in adult men with androgen deficiency syndromes: An endocrine society clinical practice guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID BONE-MINERAL DENSITY; NOCTURNAL PENILE TUMESCENCE; PLACEBO-CONTROLLED TRIAL; VISUAL EROTIC STIMULI; LEAN BODY-MASS; IMMUNODEFICIENCY-VIRUS-INFECTION; HYPOGONADAL MEN; OLDER MEN; REPLACEMENT THERAPY; TRANSDERMAL TESTOSTERONE AB Objective: The objective was to provide guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men. Participants: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a professional writer. The Task Force received no corporate funding or remuneration. Evidence: The Task Force used systematic reviews of available evidence to inform its key recommendations. The Task Force used consistent language and graphical descriptions of both the strength of recommendation and the quality of evidence, using the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation group. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions during three group meetings, several conference calls, and e-mail communications. The drafts prepared by the panelists with the help of a professional writer were reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Committee, and Council. The version approved by the Council was placed on The Endocrine Society's web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes. Conclusions: We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and in some patients by measurement of free or bioavailable testosterone level, using accurate assays. We recommend testosterone therapy for symptomatic men with androgen deficiency, who have low testosterone levels, to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 3 ng/ml without further urological evaluation, erythrocytosis (hematocrit > 50%), hyperviscosity, untreated obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score (IPSS) greater than 19, or class III or IV heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patient's preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Baylor Coll Med, Vet Affairs Med Ctr, Houston, TX 77030 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Harbor Univ Calif, Los Angeles Med Ctr, Torrance, CA 90502 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Bhasin, S (reprint author), Endocrine Soc, 8401 Connecticut Ave,Suite 900, Chevy Chase, MD 20815 USA. OI Montori, Victor/0000-0003-0595-2898 NR 109 TC 541 Z9 557 U1 3 U2 30 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 2006 VL 91 IS 6 BP 1995 EP 2010 DI 10.1210/jc.2025-2847 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050NK UT WOS:000238095000001 PM 16720669 ER PT J AU Nucera, C Vaccaro, M Moleti, M Priolo, C Tortorella, G Angioni, A Ientile, R Violi, MA Loda, M Trimarchi, F Vermiglio, F AF Nucera, Carmelo Vaccaro, Mario Moleti, Mariacarla Priolo, Carmen Tortorella, Gaetano Angioni, Adriano Ientile, Riccardo Violi, Maria Antonia Loda, Massimo Trimarchi, Francesco Vermiglio, Francesco TI Antiphospholipid antibodies syndrome associated with hyperhomocysteinemia related to MTHFR gene C677T and A1298C heterozygous mutations in a young man with idiopathic hypoparathyroidism (DiGeorge syndrome) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID 22Q11.2 DELETION SYNDROME; METHYLENETETRAHYDROFOLATE REDUCTASE; COMMON MUTATION; RISK-FACTOR; DISEASE; MANIFESTATIONS; THROMBOSIS; VASCULITIS; FEATURES; CRITERIA AB Context: Antiphospholipid syndrome (APS, or Hughes' syndrome) is a systemic autoimmune disorder characterized by antiphospholipid antibody positivity, which may lead to arterial and/or venous thrombosis. Hyperhomocysteinemia (HHcy), variously associated with 5,10-methylene tetrahydrofolate reductase (MTHFR) gene point mutations, is also implicated in thromboembolic events. The association of APS and HHcy has already been described but has never been reported in patients with DiGeorge syndrome (DGS), the most common contiguous-gene deletion syndrome (22q11.2) in humans, whose phenotype conversely includes bleeding disorders. Data Acquisition: In this report, we present the case of a 19-yr-old patient with a past medical history of learning disability and obesity affected with idiopathic hypoparathyroidism, metabolic syndrome, and diffuse vasculitis disorders. He was referred to our endocrinology clinic for the management of severe hypocalcemia. At the time of presentation he had been taking antiepileptic drugs for 2 wk and displayed facial dysmorphism ( short neck, micrognathia, a small mouth, hypoplastic nasal alae, eye hypertelorism, and low-set simple ears). DGS was suspected and confirmed by both fluorescence in situ hybridization analysis and single nucleotide polymorphism-array analysis, which revealed contiguous gene microdeletion of the chromosome 22q11.2 in the minimal DiGeorge critical region, specifically at the gene locus D22S75 (N25). Conclusions: APS, revealed by anti-beta-2-glycoprotein and anti-prothrombin antibodies positivity, and moderate HHcy related to heterozygous C677T and A1298C point mutations of the MTHFR gene were identified as a possible cause of thrombotic disorder responsible for the widespread presence of cutaneous and cerebral lesions. C1 Univ Messina, AOU Policlin G Martino, Dipartimento Clin Sperimantale Med & Farmacol, Sez Endocrinol Quarto Piano Pad H 4, I-98100 Messina, Italy. Univ Messina, Dipartimento Clin Sperimantale Med & Farmacol, Sez Dermatol, Dipartimento Med Sociale & Terr, I-98100 Messina, Italy. Univ Messina, Sez Neuropsichiatria Infantile, I-98100 Messina, Italy. Univ Messina, Dipartimento Sci Pediat Med & Chirurg, I-98100 Messina, Italy. Univ Messina, Dipartimento Biochim Fisiol & Sci Nutr, Sez Biochim & Biochim Clin, I-98100 Messina, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Regina Elena Inst Canc Res, I-00144 Rome, Italy. Osped Pediat Bambino Gesu, Ist Ricovero & Cura Carattere Sci, Lab Citogenet & Genet Mol, I-00165 Rome, Italy. RP Vermiglio, F (reprint author), Univ Messina, AOU Policlin G Martino, Dipartimento Clin Sperimantale Med & Farmacol, Sez Endocrinol Quarto Piano Pad H 4, Via Consolare Valeria 1, I-98100 Messina, Italy. EM francesco.vermiglio@unime.it RI Tortorella, Gaetano/C-9333-2011; angioni, adriano/G-1160-2014; OI Ientile, Riccardo/0000-0003-2067-0418 NR 29 TC 6 Z9 6 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2006 VL 91 IS 6 BP 2021 EP 2026 DI 10.1210/jc.2005-2782 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 050NK UT WOS:000238095000004 PM 16595601 ER PT J AU Karakousis, PC Trucksis, M Dumler, JS AF Karakousis, PC Trucksis, M Dumler, JS TI Chronic Q fever in the United States SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID COXIELLA-BURNETII; PARTURIENT CAT; ENDOCARDITIS; PNEUMONIA; VALVES; INFECTIONS; OUTBREAK AB Infections due to Coxiella burnetti, the causative agent of Q fever, are uncommon in the United States. Cases of chronic Q fever are extremely rare and most often manifest as culture-negative endocarditis in patients with underlying valvular heart disease. We describe a 31-year-old farmer from West Virginia with a history of congenital heart disease and recurrent fevers for 14 months who was diagnosed with Q fever endocarditis based on an extremely high antibody titer against Coxiella burnetti phase I antigen. Despite treatment with doxycycline, he continued to have markedly elevated Coxiella burnetii phase I antibody titers for 10 years after the initial diagnosis. To our knowledge, this case represents the longest follow-up period for a patient with chronic Q fever in the United States. We review all cases of chronic Q fever reported in the United States and discuss important issues pertaining to epidemiology, diagnosis, and management of this disease. C1 Johns Hopkins Univ, Sch Med, Ctr TB Res, Dept Med, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Karakousis, PC (reprint author), Johns Hopkins Univ, Sch Med, Ctr TB Res, Dept Med, 1550 Orleans St,Room 106, Baltimore, MD 21231 USA. EM petros@jhmi.edu NR 39 TC 38 Z9 41 U1 0 U2 3 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 2006 VL 44 IS 6 BP 2283 EP 2287 DI 10.1128/JCM.02365-05 PG 5 WC Microbiology SC Microbiology GA 053VD UT WOS:000238332900061 PM 16757641 ER PT J AU Musher, DM Nichol, AC Rueda, AM AF Musher, DM Nichol, AC Rueda, AM TI Nontypeable Haemophilus influenzae as a cause of spontaneous bacterial peritonitis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HEMOPHILUS-INFLUENZAE; STREPTOCOCCUS-PNEUMONIAE; CIRRHOTIC ASCITES; OPSONIC ACTIVITY; FLUID; SEROTYPES; BIOTYPES; CHILDREN; TRACT; FLORA AB Haemophilus influenzae rarely causes spontaneous bacterial peritonitis. We describe a typical case of spontaneous bacterial peritonitis in which the causative organism was identified as nontypeable H. influenzae, biotype III. Infection progressed despite the presence of adequate serum bactericidal antibody, probably due to the absence of complement in ascites fluid. C1 Michael E DeBakey Vet Affairs Med Ctr, Med Care Line Infect Dis Sect, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol, Houston, TX 77030 USA. Baylor Coll Med, Dept Microbiol, Houston, TX 77030 USA. RP Musher, DM (reprint author), Vet Affairs Med Ctr, Infect Dis Sect, Room 4B-370,2002 Holcombe Blvd, Houston, TX 77030 USA. EM daniel.musher@med.va.gov NR 23 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2006 VL 44 IS 6 BP 2304 EP 2306 DI 10.1128/JCM.02066-05 PG 3 WC Microbiology SC Microbiology GA 053VD UT WOS:000238332900067 PM 16757647 ER PT J AU Stone, RM AF Stone, RM TI Is intravenous arsenic trioxide a useful therapy in myelodysplastic syndromes? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID LEUKEMIA; REMISSION; GROWTH C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2006 VL 24 IS 16 BP 2414 EP 2416 DI 10.1200/JCO.2005.05.4759 PG 3 WC Oncology SC Oncology GA 048IN UT WOS:000237940900005 PM 16651644 ER PT J AU Pierce, LJ Levin, AM Rebbeck, TR Ben-David, MA Friedman, E Solin, LJ Harris, EE Gaffney, DK Haffty, BG Dawson, LA Narod, SA Olivotto, IA Eisen, A Whelan, TJ Olopade, OI Isaacs, C Merajver, SD Wong, JS Garber, JE Weber, BL AF Pierce, LJ Levin, AM Rebbeck, TR Ben-David, MA Friedman, E Solin, LJ Harris, EE Gaffney, DK Haffty, BG Dawson, LA Narod, SA Olivotto, IA Eisen, A Whelan, TJ Olopade, OI Isaacs, C Merajver, SD Wong, JS Garber, JE Weber, BL TI Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BRCA2 MUTATION CARRIERS; 20-YEAR FOLLOW-UP; PROPHYLACTIC OOPHORECTOMY; GERMLINE MUTATIONS; RISK; MASTECTOMY; WOMEN AB Purpose We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls. Methods A total of 160 BRCA 712 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls. Results There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year; estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone cophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39%. for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05). Conclusion IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who this rate remained significantly greater than in controls. Additional strategies received tamoxifen, are needed to reduce contralateral cancers in these high-risk women. C1 Univ Michigan, Sch Med, Dept Radiat Oncol, Canc & Geriatr Ctr 4308, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Sch Med, Chicago, IL 60637 USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Hamilton Reg Canc Ctr, Hamilton, ON L8V 1C3, Canada. British Columbia Canc Agcy, Victoria, BC, Canada. Chaim Sheba Med Ctr, Ramat Gan, Israel. RP Pierce, LJ (reprint author), Univ Michigan, Sch Med, Dept Radiat Oncol, Canc & Geriatr Ctr 4308, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM ljpierce@umich.edu RI Whelan, Timothy/D-3185-2017; OI Harris, Eleanor/0000-0002-7529-7473 FU NCI NIH HHS [P30 CA51008-12]; NCRR NIH HHS [M01 RR00064] NR 23 TC 174 Z9 176 U1 0 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 2006 VL 24 IS 16 BP 2437 EP 2443 DI 10.1200/JCO.2005.02.7888 PG 7 WC Oncology SC Oncology GA 048IN UT WOS:000237940900009 PM 16636335 ER PT J AU Marina, N London, WB Frazier, AL Lauer, S Rescorla, F Cushing, B Malogolowkin, MH Castleberry, RP Womer, RB Olson, T AF Marina, N London, WB Frazier, AL Lauer, S Rescorla, F Cushing, B Malogolowkin, MH Castleberry, RP Womer, RB Olson, T TI Prognostic factors in children with extragonadal malignant germ cell tumors: A pediatric intergroup study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 33rd Meeting of the International-Society-for-Paediatric-Oncology CY OCT 10-13, 2001 CL BRISBANE, AUSTRALIA SP Int Soc Paediat Oncol ID ONCOLOGY-GROUP; COMBINATION CHEMOTHERAPY; DOSE CISPLATIN; CANCER; BLEOMYCIN; ADOLESCENTS; CHILDHOOD; ETOPOSIDE; CYCLOPHOSPHAMIDE; DACTINOMYCIN AB Purpose To investigate prognostic factors for pediatric extragonadal malignant germ cell tumors (PEMGCT). Materials and Methods Between 1990 and 1996, patients with stage I through IV PEMGCT were eligible for a trial of cisplatin dose intensity. We retrospectively investigated prognostic factors for PEMGCT, including age, stage, primary site, treatment, and elevated alfa fetoprotein by univariate and multivariate analysis. Results The 165 patients had a median age of 1.9 years (range, 3 days to 18.5 years); 109 were female,and 99 had alfa fetoprotein >= 10,000. There were 30 stage I/II, 61 stage III, and 74 stage IV tumors; primary sites included 88 sacrococcygeal, 39 thoracic, and 38 others. The 5-year overall survival (OS) and event-free survival (EFS) rates with standard deviations were 83.4% +/- 3.7% and 79.0% +/- 4.1%, respectively. Univariate analysis identified age >= 12 years as a highly significant prognostic factor for EFS (5-year EFS, 48.9% +/- 15.6% v 84.1 % +/- 3.9%; P < .0001) and for OS (5-year OS, 53.7% +/- 14.9% v 88.5% +/- 3.4%; P < .0001), whereas treatment was of borderline significance (P = .0777). Multivariate Cox proportional hazards regression identified only age >= 12 years as a significant prognostic factor for EFS (P = .0002). In multivariate Cox regression for OS, the combination of age and primary site was highly significant (P < .0001). Patients >= 12 years of age with thoracic tumors had six times the risk of death compared with patients younger than 12 years with other primaries. Conclusion Age is the most predictive factor of EFS in PEMGCT. There is a significant interaction between age and primary site, suggesting that patients >= 12 years of age with thoracic tumors are a biologically distinct group. C1 Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Univ Florida, Gainesville, FL USA. Childrens Oncol Grp Stat & Data Ctr, Gainesville, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Healthcare Atlanta Egleston, Atlanta, GA USA. Indiana Univ, Riley Childrens Hosp, Indianapolis, IN 46204 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Childrens Hosp Michigan, Detroit, MI 48201 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Alabama, Birmingham, AL USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Marina, N (reprint author), Stanford Univ, Med Ctr, 1000 Welch Rd,Suite 300, Palo Alto, CA 94304 USA. EM neyssa.marina@stanford.edu NR 28 TC 24 Z9 27 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 JUN 1 PY 2006 VL 24 IS 16 BP 2544 EP 2548 DI 10.1200/JCO.2005.04.1251 PG 5 WC Oncology SC Oncology GA 048IN UT WOS:000237940900023 PM 16735707 ER PT J AU Ryan, DP Niedzwiecki, D Hollis, D Mediema, BE Wadler, S Tepper, JE Goldberg, RM Mayer, RJ AF Ryan, DP Niedzwiecki, D Hollis, D Mediema, BE Wadler, S Tepper, JE Goldberg, RM Mayer, RJ TI Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam radiation therapy in patients with locally advanced rectal cancer: Cancer and leukemia group B 89901 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID METASTATIC COLORECTAL-CANCER; HIGH-DOSE RADIATION; INFUSIONAL CHEMORADIATION; PRETREATED PATIENTS; PLUS LEUCOVORIN; TRIAL; CHEMORADIOTHERAPY; 5-FLUOROURACIL; CHEMOTHERAPY; CARCINOMA AB Purpose The addition of oxaliplatin to fluorouracil in patients with advanced colorectal cancer improves survival. This phase I/II study evaluated the addition of weekly oxaliplatin to preoperative continuous infusion fluorouracil (FU) and external-beam radiation therapy (RT) in patients with locally advanced rectal adenocarcinoma. Patients and Methods Patients with clinical T3/T4 rectal adenocarcinoma and no evidence of metastases were treated with weekly oxaliplatin, continuous infusion FU 200 mg/m(2) intravenously, and RT. A total of 6 weekly doses of oxaliplatin were planned. RT dose was 1.8 Gy/fraction to a total dose of 50.4 Gy. In the phase I portion, oxaliplatin was escalated from 30 to 60 mg/m(2). Results Forty-four patients were entered onto the study, 18 on the phase I portion and 26 on the phase 11 portion. The maximum-tolerated dose (MTD) for oxaliplatin was determined to be 60 mg/m(2). At the MTD, 12 patients experienced grade 3 or 4 diarrhea, two patients experienced grade 3 neutropenia, and one patient experienced grade 3 thrombocytopenia. Fifty-six percent of patients entered at the MTD completed all 6 weeks of oxaliplatin. Eight (25%) of 32 patients enrolled at the phase II dose experienced a pathologic complete response. Conclusion In this multicenter study, the addition of oxaliplatin to intravenous continuous infusion FU and RT for patients with locally advanced rectal cancer was associated with a high pathologic complete response rate but more toxicity than when FU is used alone. A regimen of weekly oxaliplatin, continuous infusion FU, and radiation therapy is now being evaluated by the National Surgical Adjuvant Breast and Bowel Project. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Leukemia Grp B Stat Ctr, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Chapel Hill, NC USA. Univ Missouri, Ellis Fischel Canc Ctr, Columbia, MO USA. Cornell Univ, Weill Med Coll, New York, NY USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Ctr Canc, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM dpryan@partners.org RI Goldberg , Richard/M-1311-2013 NR 23 TC 86 Z9 89 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 JUN 1 PY 2006 VL 24 IS 16 BP 2557 EP 2562 DI 10.1200/JCO.2006.05.6754 PG 6 WC Oncology SC Oncology GA 048IN UT WOS:000237940900025 ER PT J AU Krueger, G Canellos, G AF Krueger, G Canellos, G TI Where does hematology end and oncology begin? Questions of professional boundaries and medical authority SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article AB This article recounts the development of the American Society of Clinical Oncology (ASCO) and explores the role of its members in defining oncology's boundaries-boundaries dictated by scientific innovations, major changes in the structure of medical specialization, and the competing efforts of closely related professional groups. Oral histories, journal articles, and unpublished materials from the ASCO History of Oncology Archive were reviewed to analyze these events closely. In 1972, the American Board of Internal Medicine recognized medical oncology as a subspecialty, creating tensions between oncology and hematology as each discipline defended its identity. Drawing on sources produced by hematologists, historian Keith Wailoo (Wailoo, Drawing Blood, 1997) has shown that when medical oncologists claimed wide-ranging expertise over the treatment of all patients suffering from malignant disease in their pursuit of specialty status, the leukemias became contested ground. This article extends this thesis by reviewing the central role of ASCO in these events and recreating the dialogue between members of the two fields as they sought recognition at individual institutions and, more broadly, within American medicine. By acknowledging the contestation of its authority and the results of these prolonged negotiations, we can better understand the current status of oncology and its future outlook. C1 Johns Hopkins Univ, Sch Med, Dept Hist Med, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Krueger, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Hist Med, 1900 E Monument St,Room 312, Baltimore, MD 21205 USA. EM gkruege2@jhmi.edu NR 38 TC 0 Z9 0 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 2006 VL 24 IS 16 BP 2583 EP 2588 DI 10.1200/JCO.2005.04.9510 PG 6 WC Oncology SC Oncology GA 048IN UT WOS:000237940900029 PM 16735712 ER PT J AU Brawman-Mintzer, O Knapp, RG Rynn, M Carter, RE Rickels, K AF Brawman-Mintzer, Olga Knapp, Rebecca G. Rynn, Moira Carter, Rickey E. Rickels, Karl TI Sertraline treatment for generalized anxiety disorder: A randomized, double-blind, placebo-controlled study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 15th Congress of the European-College-of-Neuropsychopharmacology CY OCT 05-09, 2002 CL BARCELONA, SPAIN SP European Coll Neuropsychopharmacol ID DEPRESSION SCALE; EFFICACY; TRIAL; VENLAFAXINE; PAROXETINE AB Objective: This study assessed the efficacy and safety of sertraline in the treatment of generalized anxiety disorder (GAD). Method: The study was conducted from April 2000 to May 2002. Outpatients with DSM-IV GAD (N = 326) who satisfied inclusion/exclusion criteria and completed a 1-week screening phase were randomly assigned to 10-week double-blind treatment with flexible dosing of sertraline (50-200 mg/day) or placebo. The primary efficacy measure was change from baseline in Hamilton Rating Scale for Anxiety (HAM-A) total score. Response was defined as a 50% or greater decrease in HAM-A total score at endpoint. Results: Sertraline produced a statistically significant reduction in anxiety symptoms, as measured by HAM-A total change scores (p = .032), HAM-A psychic anxiety subscale (p = .011), and Hospital Anxiety and Depression Scale-anxiety subscale (p = .001). Response rates were significantly higher (p = .05) for the sertraline group (59.2%) compared to the placebo group (48.2%). Sertraline was well tolerated, with only sexual side effects reported significantly more often by subjects receiving sertraline than those receiving placebo. Conclusion: Despite the relatively small between-group differences, study findings suggest a role for sertraline in the acute treatment of GAD. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29406 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29406 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Brawman-Mintzer, O (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 5900 Core Rd,Suite 203, Charleston, SC 29406 USA. EM mintzero@musc.edu NR 23 TC 37 Z9 39 U1 1 U2 3 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 2006 VL 67 IS 6 BP 874 EP 881 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 059WY UT WOS:000238764100003 PM 16848646 ER PT J AU Papakostas, GI Miller, KK Petersen, T Sklarsky, KG Hilliker, SE Klibanski, A Fava, M AF Papakostas, George I. Miller, Karen K. Petersen, Timothy Sklarsky, Katherine G. Hilliker, Sarah E. Klibanski, Anne Fava, Maurizio TI Serum prolactin levels among outpatients with major depressive disorder during the acute phase of treatment with fluoxetine SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID BONE-MINERAL DENSITY; LUTEINIZING-HORMONE; SURGICAL STRESS; GALACTORRHEA; PAROXETINE; SERTRALINE; WOMEN; HYPERPROLACTINEMIA; RELEASE; ENLARGEMENT AB Objective: To determine changes in serum prolactin levels in outpatients with DSM-IV-diagnosed major depressive disorder (MDD) following a 12-week open-label trial of fluoxetine. Method: 87 outpatients enrolled in the trial had serum prolactin levels determined at baseline and during their final visit (week 12 or discontinuation visit). In addition, serum testosterone levels were measured in 44 of the 46 men during these 2 visits. Hyperprolactinemia was defined as a serum prolactin level greater than 16.5 ng/mL or 18.9 ng/mL for men and women, respectively. The study was conducted from September 1997 to March 2002. Results: Of 80 patients with normal prolactin levels at baseline, 10 (12.5%) developed hyper-prolactinemia following fluoxetine treatment. Specifically, 2 (4.5%) of 44 men and 8 (22.2%) of 36 women with normal prolactin levels at baseline developed hyperprolactinemia following treatment with fluoxetine (p = .0174 for between-gender difference). In addition, there was a significant increase in mean +/- SD serum prolactin levels following treatment with fluoxetine in all patients with normal baseline prolactin levels (6.4 +/- 3.4 to 10.0 +/- 7.0 ng/mL, p = .002). There were no significant changes from baseline in testosterone levels in men following fluoxetine treatment (448.4 +/- 139.6 to 439.5 +/- 142.1 ng/dL, p > .05; normal above 245 ng/dL), while none of the 44 men developed low testosterone levels following fluoxetine treatment. Conclusion: 4.5% of men and 22.2% of women with MDD developed new onset hyperprolactinemia following fluoxetine treatment. C1 Harvard Univ, Dept Psychiat, Depress Clin & Res Program, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Neuroendocrine Unit, Boston, MA 02115 USA. RP Papakostas, GI (reprint author), Harvard Univ, Dept Psychiat, Depress Clin & Res Program, Massachusetts Gen Hosp,Sch Med, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NCRR NIH HHS [M01-RR-01066]; NIMH NIH HHS [K23 MH069629, 5R10-MH-56057-05] NR 40 TC 20 Z9 21 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2006 VL 67 IS 6 BP 952 EP 957 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 059WY UT WOS:000238764100012 PM 16848655 ER PT J AU Targum, SD AF Targum, SD TI Evaluating rater competency for CNS clinical trials SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID RATING-SCALE AB Clinical trials rely on ratings accuracy to document a beneficial drug effect. This study examined rater competency with central nervous system rating instruments relative to previous clinical experience and participation in specific rater training programs. One thousand two hundred forty-one raters scored videotaped interviews of the Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HAM-D), and Young Mania Rating Scale (YMRS) during rater training programs conducted at 9 different investigator meetings. Scoring deviations relative to established acceptable scores were used to evaluate individual rater competency. Rater competency was not achieved by clinical experience alone. Previous clinical experience with mood-disordered patients ranged from none at all (18%) to 40 years in 1 rater. However, raters attending their first-ever training session (n 485) were not differentiated on the basis of clinical experience on the HAM-A (P = 0.054), HAM-D (P = 0.06), or YMRS (P = 0.66). Alternatively, participation in repeated rater training sessions significantly improved rater competency on the HAM-A (P = 0.002), HAM-D (P < 0.001), and YMRS (P < 0.001). Furthermore, raters with clinical experience still improved with rater training. Using 5 years of clinical experience as a minimum cutoff (n = 795), raters who had participated in 5 or more training sessions significantly outperformed comparably experienced raters attending their first-ever training session on the HAM-A (P = 0.003), HAM-D (P < 0.001), and YMRS (P < 0.001). The findings show that rater training improves rater competency at all levels of clinical experience. Furthermore, more stringent criteria for rater eligibility and comprehensive rater training programs can improve ratings competency. C1 UBC PharmaStar, Wayne, PA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Targum, SD (reprint author), Oxford BioSci, 222 Berkeley St,Suite 1650, Boston, MA 02116 USA. EM sdtargum@yahoo.com NR 9 TC 18 Z9 18 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2006 VL 26 IS 3 BP 308 EP 310 DI 10.1097/01.jcp.0000219049.33008.b7 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 044FY UT WOS:000237659000012 PM 16702896 ER PT J AU Lipkovich, I Citrome, L Perlis, R Deberdt, W Houston, JP Ahl, J Hardy, T AF Lipkovich, I Citrome, L Perlis, R Deberdt, W Houston, JP Ahl, J Hardy, T TI Early predictors of substantial weight gain in bipolar patients treated with olanzapine SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID ACUTE MANIA; I DISORDER; SCHIZOPHRENIA; OBESITY; DIVALPROEX; ANTIPSYCHOTICS; HALOPERIDOL; PREVALENCE; THERAPY; PLACEBO AB To determine predictors of substantial weight gain (SWG) during treatment of bipolar disorder with olanzapine, data were pooled from 4 long-term randomized, multicenter studies in patients with bipolar mania or mixed mania (N = 948 at initiation of olanzapine). SWG was defined as gaining 5 kg or 7% of initial weight in 30 +/- 2 weeks. Logistic regression estimated odds ratios associated with early weight gain and baseline risk factors for predicting SWG. A classification system to identify patients at risk for SWG was constructed by recursive data partitioning. Baseline characteristics significantly associated with SWG included younger age, nonwhite ethnicity, lower body mass index (BMI), nonrapid cycling, and psychotic features. Weight gain of 2 or more kg in the first 3 weeks of therapy predicted SWG by 30 weeks (sensitivity 57%; specificity = 71%). A classification system with thresholds for early weight gain, baseline BMI, and ethnicity further improved SWG predictability (sensitivity = 79%; specificity = 70%). In conclusion, patients with bipolar disorder who gained 2 to 3 kg during the first 3 weeks of treatment with olanzapine, SWG was predicted after 30 weeks of treatment. Patients with less pronounced early weight gain might still be at risk for later SWG if they have close to nonnal BMI (<= 27 kg/m(2)) at treatment initiation. C1 Eli Lilly & Co, Lilly Res Labs, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. NYU, Sch Med, New York, NY USA. Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lipkovich, I (reprint author), Eli Lilly & Co, Lilly Res Labs, Lilly Corp Ctr, Drop Code 4133, Indianapolis, IN 46285 USA. EM lipkovichia@lilly.com RI Citrome, Leslie/G-6428-2012; OI Ahl, Jonna/0000-0002-5661-6053; Citrome, Leslie/0000-0002-6098-9266 NR 24 TC 49 Z9 49 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2006 VL 26 IS 3 BP 316 EP 320 DI 10.1097/01.jcp.0000219916.88810.1c PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 044FY UT WOS:000237659000014 PM 16702898 ER PT J AU Shapiro, HL Prince, JB Ireland, R Stein, MT AF Shapiro, HL Prince, JB Ireland, R Stein, MT TI A dominating imaginary friend, cruelty to animals, social withdrawal, and growth deficiency in a 7-year-old girl with parents with schizophrenia SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE social withdrawal; imaginary companion; schizophrenia ID CHILDHOOD-ONSET SCHIZOPHRENIA; AGGRESSIVE YOUTH TRAAY; HELSINKI HIGH-RISK; PSYCHOTIC DISORDER; TREATMENT RECOMMENDATIONS; CHILDREN; COMPANIONS; HALLUCINATIONS; ANTIPSYCHOTICS; SYMPTOMS AB Tessa is a 7-year-old girl with odd behaviors, worsening over the preceding year. She spends a significant amount of time alone in her room, talking to "Richard." Her father observed that Tessa is "in her own world." In school, she often glares at the teacher and refuses to work. She is alone at recess without any real friends. Her father reports that she eats little and only after he tastes the food. She is increasingly cruel to both real and toy animals. She tied a string around her cat's neck and swung it around, saying she wanted to punish it. She was heard to say to her stuffed cat, "Die, b....; die." Richard told her to do this and other "bad" things. Tessa has not had chronic health problems or developmental concerns. During the first 18 months of life, her height was between the 5th and 10th percentiles; it declined to below the 3rd percentile over the past 2 years. Weight has been consistently between the 3rd and 5th percentiles. Tessa's parents both have been diagnosed with schizophrenia. There are at least 7 first- and second-degree relatives with the same diagnosis. Both parents cared for Tessa for 4 years with a lot of support. Then, her father left the home, but he was in contact with her while managing his own illness. When the mother's illness and compliance worsened, Tessa was removed for neglect at 5 1/2 years old. Two foster homes preceded Dad's award of sole custody 13 months ago. Mother's weekly visitations are quite upsetting to Tessa. Tessa is a verbal, solemn, small, well-dressed girl with no physical abnormalities. She talks with advanced vocabulary and syntax, with normal prosody and good conversational skills. She says Richard is a bad boy who gets her into trouble at school. She equivocates when asked if he is real or imagined or if others can see him. She says that she misses her mother. C1 All Childrens Hosp, St Petersburg, FL USA. Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33612 USA. N Shore Med Ctr, Dept Child Psychiat, Salem, MA USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Shapiro, HL (reprint author), All Childrens Hosp, St Petersburg, FL USA. NR 38 TC 12 Z9 12 U1 3 U2 12 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 2006 VL 27 IS 3 BP 231 EP 236 DI 10.1097/00004703-200606000-00010 PG 6 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 056CK UT WOS:000238498500008 PM 16775522 ER PT J AU Bruce, BB Henry, ME Greer, DM AF Bruce, BB Henry, ME Greer, DM TI Ischemic stroke after electroconvulsive therapy SO JOURNAL OF ECT LA English DT Article DE ischemic; stroke; electroconvulsive therapy ID ECT AB Stroke is an exceptionally rare complication of electroconvulsive therapy since modem anesthesia and appropriate medical screening were instituted in the 1950s. Postictal focal neurological deficits mimicking stroke are common, but the advent of acute stroke therapies has made the differentiation of these from true cerebrovascular events critical. We present the first case report of ischemic stroke after electroconvulsive therapy with radiographic confirmation. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, Dept Neurol, ACC 835,55 Fruit St, Boston, MA 02114 USA. EM dgreer@partners.org OI Bruce, Beau/0000-0003-3003-2962 NR 7 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD JUN PY 2006 VL 22 IS 2 BP 150 EP 152 DI 10.1097/00124509-200606000-00015 PG 3 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 059GE UT WOS:000238720500014 PM 16801834 ER PT J AU Kalva, SP Wicky, S Waltman, AC Athanasoulis, CA AF Kalva, SP Wicky, S Waltman, AC Athanasoulis, CA TI TrapEase vena cava filter: Experience in 751 patients SO JOURNAL OF ENDOVASCULAR THERAPY 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 DE venous thromboembolism; inferior vena cava; IVC filters; pulmonary embolism; deep venous thrombosis; complications ID PRELIMINARY CLINICAL-EXPERIENCE; FEMORAL VEIN-THROMBOSIS; FOLLOW-UP; VENOUS THROMBOEMBOLISM; PULMONARY-EMBOLISM; GREENFIELD FILTER; PERMANENT; EFFICACY; COMPLICATIONS; INTERRUPTION AB Purpose: To evaluate the clinical safety and efficacy of the TrapEase vena Cava filter in a 4-year single-center experience. Methods: The clinical and imaging data of 751 patients (384 men; mean age 64 years, range 16-99) who had a TrapEase inferior vena Cava (IVC) filter placed between January 1, 2001, and December 31, 2004, were reviewed retrospectively. More than a third of patients (297, 39.5%) presented with pulmonary embolism (PE), 188 (25.0%) had deep vein thrombosis (DVT), 40 (5.3%) had both PE and DVT, and the rest (226, 30.1%) had other symptoms. Indications for filter placement were contraindication to anticoagulation (461, 61.4%), complication of anticoagulation (42, 5.6%), failure of anticoagulation (39, 5.2%), and prophylaxis (209, 27.8%). Filters were placed in the infrarenal (n=738) or suprarenal (n=13) position through a femoral (n=729) or jugular vein (n=22) approach. Follow-up computed tomographic (CT) scans of the chest and abdomen were evaluated for recurrent PE and filter-related complications, respectively. Results: Three (0.4%) patients developed groin hematoma. During a mean 295-day clinical follow-up (range 1-1677), 55 (7.5%) patients developed symptoms of PE, and 1 (0.1%) death was attributed to PE. Chest CT performed for various clinical indications in 219 patients at a mean 192 days (range 1-1346) showed PE in 15 (6.8%) patients; 10 were symptomatic and 5 asymptomatic, but there were no fatalities. Follow-up abdominal CT (n=270) at a mean 189 days (range 1-1415) showed fracture of filter components in 8 (3.0%), thrombus within the filter in 68 (25.2%), thrombus extending beyond the filter in 4 (1.5%), near total caval occlusion in 2 (0.7%), and no cases of migration. Conclusion: The TrapEase vena Cava filter is effective in the prevention of pulmonary embolism, with minimal complications. C1 Massachusetts Gen Hosp, Dept Radiol, Div Cardiovasc Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kalva, SP (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Cardiovasc Imaging & Intervent, GRB 290, Boston, MA 02114 USA. EM skalva@partners.org NR 25 TC 27 Z9 35 U1 0 U2 1 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 2006 VL 13 IS 3 BP 365 EP 372 DI 10.1583/05-1741.1 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 053VP UT WOS:000238334300013 PM 16784325 ER PT J AU Groeneveld, PW Sonnad, SS Lee, AK Asch, DA Shea, JE AF Groeneveld, PW Sonnad, SS Lee, AK Asch, DA Shea, JE TI Racial differences in attitudes toward innovative medical technology SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Academy-Health Annual Research Meeting CY JUN, 2005 CL Boston, MA SP Acad Hlth DE African Americans; technology; medical; attitude; diffusion of innovation; veterans ID CORONARY-REVASCULARIZATION; ADOPTION; DISPARITIES; CARE AB BACKGROUND: New medical technologies are used at different rates among whites and blacks. This variation may be partially explained by racial differences in patient innovativeness-the propensity of patients to adopt unfamiliar therapies. OBJECTIVE: To measure how innovativeness varies among patients and how it may influence patients' attitudes toward new medical technologies. DESIGN: Cross-sectional survey. PARTICIPANTS: Primary care patients (n=171-108 blacks, 63 whites) at an urban Veterans Affairs medical center. MEASUREMENTS: Respondents answered questions about their general innovativeness and innovativeness regarding medical technology, and they responded to a vignette describing either a hypothetical new prescription drug or implantable device. RESULTS: There were no significant racial differences in general innovativeness, but whites had higher medical technology innovativeness (P=.001). Whites were also more likely to accept the new prescription drug (P =.003), but did not differ from blacks in acceptance of the new implantable device. In multivaiiate analyses, lower medical technology innovativeness scores among blacks were significantly associated with less favorable reactions to both the prescription drug (P <.001) and the medical device (P <.001). In contrast, although whites with lower medical technology innovativeness were similarly less inclined to accept the new implantable device (P=.02), there was no significant association between medical technology innovativeriess and positive attitudes to the new prescription drug among whites. CONCLUSIONS: Blacks and whites have differing attitudes toward medical innovation. These differences are associated with significant racial differences in response to particular health care technologies. These findings suggest potentially remediable causes for racial differences in the utilization of innovative medical technologies. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. RP Groeneveld, PW (reprint author), 1229 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM peter.groenevetd@med.va.gov OI Asch, David/0000-0002-7970-286X NR 23 TC 21 Z9 21 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2006 VL 21 IS 6 BP 559 EP 563 DI 10.1111/j.1525-1497.2006.00453.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 051FU UT WOS:000238147800003 PM 16808736 ER PT J AU Levine, RB Haidet, P Kern, DE Beasley, BW Bensinger, L Brady, DW Gress, T Hughes, J Marwaha, A Nelson, J Wright, SM AF Levine, Rachel B. Haidet, Paul Kern, David E. Beasley, Brent W. Bensinger, Liso Brady, Donald W. Gress, Todd Hughes, Jennifer Marwaha, Ajay Nelson, Jennifer Wright, Scott M. TI Personal growth during internship - A qualitative analysis of interns' responses to key questions SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE graduate medical education; personal growth; qualitative research ID MEDICINE RESIDENCY PROGRAM; PATIENT-CARE; REFLECTION; PHYSICIANS; AWARENESS; STUDENTS; DOCTORS; STRESS AB BACKGROUND: During clinical training, house officers frequently encounter intense experiences that may affect their personal growth. The purpose of this study was to explore processes related to personal growth during internship. DESIGN. Prospective qualitative study conducted over the course of internship. PARTICIPANTS: Thirty-two postgraduate year (PGY)-1 residents from 9 U.S. internal medicine training programs. APPROACH: Every 8 weeks, interns responded by e-mail to an open-ended question related to personal growth. Content analysis methods were used to analyze the interns' writings to identify triggers, facilitators, and barriers related to personal growth. RESULTS: Triggers for personal growth included caring for critically ill or dying patients, receiving feedback, witnessing unprofessional behavior, experiencing personal problems, and dealing with the increased responsibility of internship. Facilitators of personal growth included supportive relationships, reflection, and commitment to core values. Fatigue, lack of personal time, and overwhelming work were barriers to personal growth. The balance between facilitators and barriers may dictate the extent to which personal growth occurs. CONCLUSIONS: Efforts to support personal growth during residency training include fostering supportive relationships, encouraging reflection, and recognizing interns' core values especially in association with powerful triggers. C1 Johns Hopkins Bayview Med Ctr, Div Gen Internal Med, Baltimore, MD 21224 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Missouri, Kansas City, MO 64110 USA. Mt Sinai Sch Med, New York, NY USA. Emory Univ, Atlanta, GA 30322 USA. Marshall Univ, Joan C Edwards Sch Med, Huntington, WV USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. York Hosp, York, PA USA. Highland Gen Hosp, Oakland, CA USA. RP Levine, RB (reprint author), Johns Hopkins Bayview Med Ctr, Div Gen Internal Med, 4940 Eastern Ave,Bldg B2N,Room 235, Baltimore, MD 21224 USA. EM rlevine@jhmi.edu NR 33 TC 17 Z9 17 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2006 VL 21 IS 6 BP 564 EP 569 DI 10.1111/j.1525-1497.2006.00383.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 051FU UT WOS:000238147800004 PM 16808737 ER PT J AU Bokhour, BG Berlowitz, DR Long, JA Kressin, NR AF Bokhour, BG Berlowitz, DR Long, JA Kressin, NR TI How do providers assess antihypertensive medication adherence in medical encounters? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hypertension; medication adherence; provider-patient communication ID DOCTOR-PATIENT COMMUNICATION; HIGH BLOOD-PRESSURE; DECISION-MAKING; HEALTH LITERACY; HYPERTENSION; PREVENTION; AMERICANS; ILLNESS; CARE AB BACKGROUND: Poor adherence to antihypertensives has been shown to be a significant factor in poor blood pressure (BP) control. Providers' communication with patients about their medication-taking behavior may be central to improving adherence. OBJECTIVE: The goal of this study was to characterize the ways in which providers ask patients about medication taking. DESIGN. Clinical encounters between primary care providers and hypertensive patients were audiotaped at 3 Department of Veterans' Affairs medical centers. PARTICIPANTS: Primary care providers (n=9) and African-American and Caucasian patients (n =38) who were diagnosed with hypertension (HTN). APPROACH: Transcribed audiotapes of clinical encounters were coded by 2 investigators using qualitative analysis based on sociolinguistic techniques to identify ways of asking about medication taking. Electronic medical records were reviewed after the visit to determine the BP measurement for the day of the taped encounter. RESULTS: Four different aspects of asking about medication were identified: structure, temporality, style and content. Open-ended questions generated the most discussion, while closed-ended declarative statements led to the least discussion. Collaborative style and use of lay language were also seen to facilitate discussions. In 39% of encounters, providers did not ask about medication taking. Among patients with uncontrolled HTN, providers did not ask about medications 33% of the time. CONCLUSION., Providers often do not ask about medication-taking behavior, and may not use the most effective communication strategies when they do. Focusing on the ways in which providers ask about patients' adherence to medications may improve BP control. C1 ENRM Vet Hosp 152, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Philadelphia Va Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Leonard Davis Inst Hlth Econ, Philadelphia, PA USA. RP Bokhour, BG (reprint author), ENRM Vet Hosp 152, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd, Bedford, MA 01730 USA. EM bokhour@bu.edu OI Bokhour, Barbara/0000-0001-8238-0745; Kressin, Nancy/0000-0003-2767-4286 NR 30 TC 39 Z9 40 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2006 VL 21 IS 6 BP 577 EP 583 DI 10.1111/j.1525-1497.2006.00397.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 051FU UT WOS:000238147800006 PM 16808739 ER PT J AU Mularski, RA White-Chu, F Overbay, D Miller, L Asch, SM Ganzini, L AF Mularski, RA White-Chu, F Overbay, D Miller, L Asch, SM Ganzini, L TI Measuring pain as the 5th vital sign does not improve quality of pain management SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE pain; quality of health care; outcome and process assessment (health care); pain measurement; quality indicators ID HEALTH-CARE-SYSTEM; CANCER PAIN; OF-CARE; VALIDATION; GUIDELINES; ADULTS AB BACKGROUND: To improve pain management, the Veterans Health Administration launched the "Pain as the 5th Vital Sign" initiative in 1999, requiring a pain intensity rating (0 to 10) at all clinical encounters. OBJECTIVE: To measure the initiative's impact on the quality of pain management. DESIGN: We retrospectively reviewed medical records at a single medical center to compare providers' pain management before and after implementing the initiative and performed a subgroup analysis of patients reporting substantial pain ( 4) during a postimplementation visit. PARTICIPANTS: Unique patient visits selected from all 15 primary care providers of a general medicine outpatient clinic. MEASUREMENTS: We used 7 process indicators of quality pain management, based on appropriately evaluating and treating pain, to assess 300 randomly selected visits before and 300 visits after implementing the pain initiative. RESULTS: The quality of pain care was unchanged between visits before and after the pain initiative (P >.05 for all comparisons): subjective provider assessment (49.3% before, 48.7% after), pain exam (26.3%, 26.0%), orders to assess pain (11.7%, 8.3%), new analgesic (8.7%, 11.0%), change in existing analgesics (6.7%, 4.3%), other pain treatment (11.7%, 13.7%), or follow-up plans (10.0%, 8.7%). Patients (n=79) who reported substantial pain often did not receive recommended care: 22% had no attention to pain documented in the medical record, 27% had no further assessment documented, and 52% received no new therapy for pain at that visit. CONCLUSIONS: Routinely measuring pain by the 5th vital sign did not increase the quality of pain management. Patients with substantial pain documented by the 5th vital sign often had inadequate pain management. C1 VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RAND Hlth, Los Angeles, CA USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Sch Nursing, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Mental Hlth Div, Portland, OR USA. RP Mularski, RA (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd,Mailcode 111G, Los Angeles, CA 90073 USA. EM Richard.Mularski@med.va.gov FU NINR NIH HHS [1P20NR0780] NR 29 TC 129 Z9 133 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2006 VL 21 IS 6 BP 607 EP 612 DI 10.1111/j.1525-1497.2006.00415.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 051FU UT WOS:000238147800011 PM 16808744 ER PT J AU Kharod, BV Johnson, PB Nesti, HA Rhee, DJ AF Kharod, BV Johnson, PB Nesti, HA Rhee, DJ TI Effect of written instructions on accuracy of self-reporting medication regimen in glaucoma patients SO JOURNAL OF GLAUCOMA LA English DT Article DE medication compliance; glaucoma; written instructions; self reporting; medication regimen AB Purpose: Our purpose was to evaluate the accuracy of self-reporting of the prescribed medication regimen in a glaucoma population, identify contributing factors, and assess the effect of written instructions. Methods and Materials: All patients at an urban resident glaucoma clinic were offered participation in this prospective, case-controlled study. Two trained interviewers administered a confidential questionnaire consisting of six questions regarding the name and dosage of ophthalmic medications, education level, ability to read, and age. A verbatim response for each question was recorded on the questionnaire. At the end of the visit, patients were given a written chart describing their ophthalmic medications, frequency, and dosage. At their next scheduled visit, the same questionnaire was repeated. The patients' responses from both visits were compared with the regimen they were prescribed and with each other. This information was used to determine the accuracy of reporting medications. Results: A total of 193 patients were enrolled in the study over a 10-month period; 164 patients completed both phases (85% completion rate). The study population consisted of 85 women and 79 men with a mean age of 68.40 +/- 11.6 years. Eighty-four patients had attained less than 12th grade education and 80 had completed high school. At the first visit, 66 patients (40%) showed less than 100% accuracy. Forty-nine of 84 (58%) patients who had not completed high school education showed less than 100% accuracy with a mean score of 65% (P = 0.001), whereas 17 of 80 (21%) of patients who had completed high school showed less than 100% accuracy with a mean score of 87% (P = 0.001). After written instruction, the accuracy of reporting improved by 23.36 +/- 30.8 percentile points in patients without completion of high school education and improved by 8.46 +/- 21.7 percentile points in patients who had completed high school (P < 0.001). The mean number of ophthalmic medications prescribed was 2.10 +/- 0.93 (range 1 to 4). Patients on one medication had 100% accuracy in reporting 82% of the time, whereas those with four medications had 100% accuracy 21% of the time. Gender, age, and race of the patient were not correlated with the accuracy of self-reporting (P > 0.05). Conclusion: The education level of the patient and the number of medications showed direct correlation with patients' ability to report medications accurately. Patients showed improvement in accuracy of reporting medications when given written instructions about their regimen, regardless of their level of education or number of medications. C1 Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. Wills Eye Hosp & Res Inst, William & Anna Goldberg Glaucoma Serv, Philadelphia, PA USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com FU NEI NIH HHS [EY 13997] NR 9 TC 21 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD JUN PY 2006 VL 15 IS 3 BP 244 EP 247 DI 10.1097/01.ijg.0000212213.18018.8f PG 4 WC Ophthalmology SC Ophthalmology GA 052OO UT WOS:000238243200011 PM 16778648 ER PT J AU Offner, H Subramanian, S Parker, SM Wang, CH Afentoulis, ME Lewis, A Vandenbark, AA Hurn, PD AF Offner, H Subramanian, S Parker, SM Wang, CH Afentoulis, ME Lewis, A Vandenbark, AA Hurn, PD TI Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MONOCYTE CHEMOATTRACTANT PROTEIN-1; MESSENGER-RNA EXPRESSION; MIDDLE CEREBRAL-ARTERY; RAT ISCHEMIC CORTEX; TRANSCRIPTION FACTOR; IMMUNE PATHOLOGY; GENE-EXPRESSION; AUTOIMMUNITY; INJURY AB Induction of stroke not only produces local ischemia and brain damage, but also has profound effects on peripheral immune responses. In the current study, we evaluated effects on spleen and blood cells 4 days after stroke induction. Surprisingly, there was a less inflammatory cytokine profile in the middle cerebral artery occlusion-affected right brain hemisphere at 96 h compared with earlier time points. Moreover, our results demonstrate that stroke leads to splenic atrophy characterized by a reduction in organ size, a drastic loss of splenocyte numbers, and induction of annexin V+ and TUNEL+ cells within the spleen that are in the late stages of apoptosis. The consequence of this process was to reduce T cell proliferation responses and secretion of inflammatory cytokines, resulting in a state of profound immunosuppression. These changes produced a drastic reduction in B cell numbers in spleen and blood, and a novel increase in CD4(+)FoxP3(+) regulatory T cells. Moreover, we detected a striking increase in the percentage of nonapoptotic CD11b(+) VLA-4-negative macrophages/monocytes in blood. Immunosuppression in response to brain injury may account for the reduction of inflammatory factors in the stroke-affected brain, but also potentially could curtail protective immune responses in the periphery. These findings provide new evidence to support the contention that damage to the brain caused by cerebral ischemia provides a powerful negative signal to the peripheral immune system that ultimately induces a drastic state of immunosuppression caused by cell death as well as an increased presence of CD4(+)FoxP3(+) regulatory T cells. C1 Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland Vet Affairs Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NCRR NIH HHS [RR00163]; NINDS NIH HHS [NS33668, NS49210, R01 NS076013]; NINR NIH HHS [NR03521] NR 35 TC 191 Z9 198 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 2006 VL 176 IS 11 BP 6523 EP 6531 PG 9 WC Immunology SC Immunology GA 045PN UT WOS:000237754200016 PM 16709809 ER PT J AU Touma, M Chang, HC Sasada, T Handley, M Clayton, LK Reinherz, EL AF Touma, M Chang, HC Sasada, T Handley, M Clayton, LK Reinherz, EL TI The TCR C beta FG loop regulates alpha beta T cell development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID POSITIVE SELECTION; ALLELIC EXCLUSION; ANTIGEN RECEPTOR; PRE-TCR; SIGNAL-TRANSDUCTION; FUNCTIONAL-ANALYSIS; CHAIN LACKING; ZETA-CHAIN; COMPLEX; MICE AB The TCRP chain constant domain contains an unusually elongated, solvent-exposed FG loop. This structural element forms one component of an alpha beta TCR cavity against which CD3 epsilon gamma may abut to facilitate Ag-specific signaling. Consistent with this notion, in the present study we show that N15 alpha beta TCR transfectants expressing a FG loop-deleted chain (beta Delta FG) stimulate less tyrosine protein phosphorylation than those bearing a wild-type beta-chain (beta wt) upon TCR cross-linking. Furthermore, coimmunoprecipitation studies suggest a weakened association between the CD3 epsilon gamma heterodimer and the beta-chain in TCR complexes containing the beta Delta FG variant. To further investigate the biologic role of the C beta FG loop in development, we competitively reconstituted the thymus of Ly5 congenic or RAG-2(-/-) mice using bone marrow cells from beta wt or beta Delta FG transgenic C57BL/6 (B6) mice. Both beta wt and beta Delta FG precursor cells generate thymocytes representative of all maturational stages. However, beta Delta FG-expressi'ng thymocytes dominate during subsequent development, resulting in an excess of beta Delta FG-expressing peripheral T cells with reduced proliferative and cytokine production abilities upon TCR stimulation. Collectively, our results show that the unique C beta FG loop appendage primarily controls alpha beta T cell development through selection processes. C1 Dana Farber Canc Inst, Lab Immunobiol, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Lab Immunobiol, Dept Med Oncol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [AI19807, AI45789] NR 51 TC 23 Z9 23 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 JUN 1 PY 2006 VL 176 IS 11 BP 6812 EP 6823 PG 12 WC Immunology SC Immunology GA 045PN UT WOS:000237754200048 PM 16709841 ER PT J AU Medoff, BD Wain, JC Seung, E Jackobek, R Means, TK Ginns, LC Farber, JM Luster, AD AF Medoff, BD Wain, JC Seung, E Jackobek, R Means, TK Ginns, LC Farber, JM Luster, AD TI CXCR3 and its Ligands in a murine model of obliterative bronchiolitis: Regulation and function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FACTOR-KAPPA-B; HEART-LUNG TRANSPLANTATION; ACUTE ALLOGRAFT-REJECTION; CHEMOKINE RECEPTOR CXCR3; GAMMA-INDUCIBLE PROTEIN; IFN-GAMMA; T-CELL; INTERFERON-GAMMA; REPERFUSION INJURY; MYD88-INDEPENDENT PATHWAY AB Lung transplantation remains the only effective therapy for patients with end-stage lung disease, but survival is limited by the development of obliterative bronchiolitis (OB). The chemokine receptor CXCR3 and two of its ligands, CXCL9 and CXCL10, have been identified as important mediators of OB. However, the relative contribution of CXCL9 and CXCL10 to the development of OB and the mechanism of regulation of these chemokines has not been well defined. In this study, we demonstrate that CXCL9 and CXCL10 are up-regulated in unique patterns following tracheal transplantation in mice. In these experiments, CXCL9 plant, while CXCL10 expression peaked at 1 day and then again 7 days posttransplant. expression peaked 7 days posttrans Expression of CXCL10 was also up-regulated in a novel murine model of lung ischemia, and in bronchoalveolar lavage fluid taken from human lungs 24 h after lung transplantation. In further analysis, we found that 3 h after transplantation CXCL10 is donor tissue derived and not dependent on IFN-gamma or STAT1, while 24 h after transplantation CXCL10 is from recipient tissue and regulated by IFN-gamma and STAT1. Expression of both CXCL9 and CXCL10 7 days posttransplant is regulated by IFN-gamma and STAT1. Finally, we demonstrate that deletion of CXCR3 in recipients reduces airway obliteration. However, deletion of either CXCL9 or obliteration. These data show that in this murine model of obliterative bronchiolitis, these che-mokines are differentially regulated following transplantation, and that deletion of either chemokine alone does not affect the development of airway obliteration. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Thorac Surg, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, CNY 8301,149 13th St, Charlestown, MA 02129 USA. EM luster.andrew@mgh.harvard.edu FU NHLBI NIH HHS [K08 HL072775]; NIAID NIH HHS [R01 AI050892] NR 64 TC 35 Z9 36 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2006 VL 176 IS 11 BP 7087 EP 7095 PG 9 WC Immunology SC Immunology GA 045PN UT WOS:000237754200078 PM 16709871 ER PT J AU d'Avila, A Thiagalingam, A Holmvang, G Houghtaling, C Ruskin, JN Reddy, VY AF d'Avila, Andre Thiagalingam, Aravinda Holmvang, Godtfred Houghtaling, Christopher Ruskin, Jeremy N. Reddy, Vivek Y. TI What is the most appropriate energy source for aortic cusp ablation? A comparison of standard RF, cooled-tip RF and cryothermal ablation SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE ablation; arrhythmia; catheterization; electrophysiology; pericardium; aorta; cryoablation; fibrillation ID RADIOFREQUENCY CATHETER ABLATION; VENTRICULAR OUTFLOW TRACT; ATRIAL-FIBRILLATION; CORONARY-ARTERY; TACHYCARDIA; SINUS; CRYOABLATION AB Background Certain tachycardias can be eliminated by catheter ablation from within the base of the aortic valve (AV) cusps but the high blood flow and proximity to the coronary arteries create unique challenges. Standard radiofrequency (RF) energy, cooled-tip RF energy or cryothermal energy were compared to determine the optimal ablation modality. Materials and methods Experiments were conducted using adult swine or goats (15 animals). Ablation lesions were placed using either: temperature-controlled RF (4 mm-tip catheter; 60 degrees C/60 s), cooled-tip RF (4 mm-tip catheter with internal saline circulation at 0.6 ml/s; 40 degrees C/60 s), or cryoablation (6 mm-tip spot cryocatheter; <-75 degrees C/4 min). Animals were sacrificed 1 h after the last application and lesions were subject to pathological analysis. Results Standard RF and cryoablation created similar depth lesions in the right coronary cusp (4.2 +/- 1.3 and 3.4 +/- 0.5 mm, respectively) but cryoablation was unable to create any visible lesions in the non-coronary cusp. Cooled tip ablation created larger ablation lesions in the right coronary cusp (5.25 +/- 0.5) and fully transmural left atrial ablation lesions after ablation in the noncoronary cusp. Acute damage to the cusps was not noted with any ablation modality. Disruption of elastic fibers in the aortic media was seen after standard and cooled tip radiofrequency ablation but not cryoablation. ConclusionCryoablation within the AV cusps created similar sized lesions to standard RF ablation without evidence of elastic fibre disruption and may therefore be an appropriate first line ablation modality. Cooled-tip ablation created larger ablation lesions and therefore may be required if cryoablation is ineffective. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MRI Unit, Boston, MA 02114 USA. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St GRB 109, Boston, MA 02114 USA. EM vreddy@partners.org RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 FU NHLBI NIH HHS [HL68064-02] NR 16 TC 18 Z9 18 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 2006 VL 16 IS 1 BP 31 EP 38 DI 10.1007/s10840-006-9006-8 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 105FD UT WOS:000242014700005 PM 17029021 ER PT J AU Fan, JH Guan, SX Cheng, CF Cho, M Fields, JW Chen, M Denning, MF Woodley, DT Li, W AF Fan, Jianhua Guan, Shengxi Cheng, Chieh-Fang Cho, Michele Fields, Joshua W. Chen, Mei Denning, Mitchell F. Woodley, David T. Li, Wei TI PKC delta clustering at the leading edge and mediating growth factor-enhanced, but not ECM-initiated, dermal fibroblast migration SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID PROTEIN-KINASE-C; HUMAN KERATINOCYTE MIGRATION; VASCULAR SMOOTH-MUSCLE; TYROSINE PHOSPHORYLATION; CELL MOTILITY; INDUCED-DIFFERENTIATION; INDUCED APOPTOSIS; GENE-EXPRESSION; ACTIVATION; RECEPTOR AB We have previously shown that the immobilized extracellular matrices (ECMs) initiate cell migration and soluble growth factors (GFs) further enhance ECM-initiated cell migration. GFs alone cannot initiate cell migration. To further investigate the specificity of the two signaling mechanisms, we focused on the protein kinase C (PKC) family genes in primary human dermal fibroblasts (DFs). We here show that platelet-derived growth factor-BB (PDGF-BB) strongly stimulates membrane translocation and leading edge clustering of protein kinase C delta(PKC delta). In contrast, attachment to collagen matrix alone does not cause the translocation. Although the kinase function of PKC delta is dispensable for initial membrane translocation, it is critical for its sustained presence at the cells's leading edge. Blockade of endogenous PKC delta signaling with dominant-negative kinase-defective PKC (PKC delta-KD) or PKC delta-small interfering RNA (siRNA) completely inhibited PDGF-BB-stimulated DF migration. In contrast, neither PKC delta-KD nor PKC delta-siRNA affected collagen-induced initiation of DF migration. Overexpression of a constitutively activated PKC delta(PKC delta-R144/145A) partially mimics the effect of PDGF-BB. However, PKC delta-KD, PKC delta-siRNA, or PKC delta-R144/145A does not affect PDGF-BB-stimulated activation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase1/2, or c-Jun N-terminal kinase. Instead, inhibition of PKC delta blocks PDGF-BB-stimulated activation of signal transducer and activator of transcription 3 (Stat3). This study unveiled the specificity of PKC delta in the control of DF migration. C1 Univ So Calif, Keck Sch Med, Dept Dermatol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Greater Los Angeles Vet Adm Hlth Syst, Los Angeles, CA USA. Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. RP Li, W (reprint author), Univ So Calif, Keck Sch Med, Dept Dermatol, Los Angeles, CA 90033 USA. EM dwoodley@usc.edu; wli@usc.edu FU NIAMS NIH HHS [AR46538, GM/AR67100-01] NR 65 TC 13 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 2006 VL 126 IS 6 BP 1233 EP 1243 DI 10.1038/sj.jid.5700149 PG 11 WC Dermatology SC Dermatology GA 062TZ UT WOS:000238968800012 PM 16543902 ER PT J AU Arbiser, JL Govindarajan, B Battle, TE Lynch, R Frank, DA Ushio-Fukai, M Perry, BN Stern, DF Bowden, GT Liu, AQ Klein, E Kolodziejski, PJ Eissa, NT Hossain, CF Nagle, DG AF Arbiser, Jack L. Govindarajan, Baskaran Battle, Traci E. Lynch, Rebecca Frank, David A. Ushio-Fukai, Masuko Perry, Betsy N. Stern, David F. Bowden, G. Tim Liu, Anquan Klein, Eva Kolodziejski, Pawel J. Eissa, N. Tony Hossain, Chowdhury F. Nagle, Dale G. TI Carbazole is a naturally occurring inhibitor of angiogenesis and inflammation isolated from antipsoriatic coal tar SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; NITRIC-OXIDE; IN-VIVO; PSORIATIC SKIN; T-CELLS; DOWN-REGULATION; MOUSE MODEL; KAPPA-B; STAT3 AB Coal tar is one of the oldest and an effective treatment for psoriasis. Coal tar has been directly applied to the skin, or used in combination with UV light as part of the Goeckerman treatment. The use of coal tar has caused long-term remissions in psoriasis, but has fallen out of favor because the treatment requires hospitalization and coal tar is poorly acceptable aesthetically to patients. Thus, determining the active antipsoriatic component of coal tar is of considerable therapeutic interest. We fractionated coal tar into its components, and tested them using the SVR angiogenesis inhibitor assay. Treatment of SVR endothelial cells with coal tar fractions resulted in the isolation of a single fraction with antiangiogenic activity. The active antiangiogenic compound in coal tar is carbazole. In addition to antiangiogenic activity, carbazole inhibited the production of inflammatory IL-15 by human mononuclear cells. IL-15 is elevated in psoriasis and is thought to contribute to psoriatic inflammation. Carbazole treatment also reduced activity of inducible nitric oxide synthase ( iNOS), which is proinflammatory and elevated in psoriasis. The effect of carbazole on upstream pathways in human psoriasis was determined, and carbazole was shown to inhibit signal transducer and activator of transcription (stat)3-mediated transcription, which has been shown to be relevant in human psoriasis. IL-15, iNOS, and stat3 activation require the activation of the small GTPase rac for optimal activity. Carbazole was found to inhibit rac activation as a mechanism for its inhibition of downstream inflammatory and angiogenic pathways. Given its antiangiogenic and anti-inflammatory activities, carbazole is likely a major component of the antipsoriatic activity of coal tar. Carbazole and derivatives may be useful in the therapy of human psoriasis. C1 Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. Emory Univ, Dept Cardiol, Sch Med, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Dept Pathol, New Haven, CT USA. Univ Arizona, Sch Med, Arizona Canc Ctr, Tucson, AZ USA. Karolinska Inst, Microbiol & Tumor Ctr, Stockholm, Sweden. Baylor Coll Med, Houston, TX 77030 USA. Univ Mississippi, Sch Pharm, Dept Pharmacognosy, Mississippi State, MS USA. RP Arbiser, JL (reprint author), Emory Univ, Sch Med, Dept Dermatol, WMB 5309, Atlanta, GA 30322 USA. EM jarbise@emory.edu FU NCI NIH HHS [R01 CA098787-02, R01 CA098787, R01 CA098787-01A2, R01CA45708]; NHLBI NIH HHS [R01 HL075421, R01HL069033]; NIAMS NIH HHS [R01 AR 050727, R01AR 47901, P30 AR 42687] NR 48 TC 29 Z9 29 U1 1 U2 4 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 2006 VL 126 IS 6 BP 1396 EP 1402 DI 10.1038/sj.jid.5700276 PG 7 WC Dermatology SC Dermatology GA 062TZ UT WOS:000238968800034 PM 16614726 ER PT J AU Sorensen, AG AF Sorensen, AG TI Future prospects for MRI in the clinic SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE fMRI; clinical; editorial; future; therapy development ID 7 TESLA; BRAIN AB Functional MRI (fMRI) has tremendous clinical potential that is as vet unrealized. There are tremendous unmet medical needs that fMRI could address with significant benefit to human health. However, both medical and technical barriers prevent this benefit from accruing today. Technical barriers may be the reflexive focus of the current practitioners of fMRI. a technically savvy group. However, the real challenge lies in the medical realm, and this will require multidisciplinary and interdisciplinary work since the technical aspects of fMRI are ahead of the medical aspects. This can be seen in a range of diseases from Alzheimer's disease to schizophrenia to ischemic stroke: in each case our ability to image changes with fMRI outstrips our ability to do anything useful for the patient with them. Diagnostic imaging will always be linked in the clinic to therapeutic choices, and therefore the most powerful approach to link fMRI more directly to the clinic will be to tie fMRI to therapy development and implementation. C1 Harvard Univ, MIT, Sch Med, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Boston, MA 02129 USA. Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Boston, MA 02129 USA. RP Sorensen, AG (reprint author), Harvard Univ, MIT, Sch Med, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Boston, MA 02129 USA. EM sorensen@nmr.mgh.harvard.edu NR 6 TC 8 Z9 8 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUN PY 2006 VL 23 IS 6 BP 941 EP 944 DI 10.1002/jmri.20589 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 050EN UT WOS:000238070400015 PM 16649201 ER PT J AU Niendorf, KB Goggins, W Yang, G Tsai, KY Shennan, M Bell, DW Sober, AJ Hogg, D Tsao, H AF Niendorf, KB Goggins, W Yang, G Tsai, KY Shennan, M Bell, DW Sober, AJ Hogg, D Tsao, H TI MELPREDICT: a logistic regression model to estimate CDKN2A carrier probability SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID GERMLINE MUTATIONS; PANCREATIC-CANCER; PRONE FAMILIES; MELANOMA; RISK; P16; PREDISPOSITION; SUSCEPTIBILITY; PREVALENCE; STATEMENT AB Background: Heritable alterations in CDKN2A account for a subset of familial melanoma cases although no robust method exists to identify those at risk of being a mutation carrier. Methods: We set out to construct a model for estimating CDKN2A mutation carrier probability using a cohort of 116 consecutive familial cutaneous melanoma patients evaluated at Massachusetts General Hospital Pigmented Lesion Center between April 2001 and September 2004. Germline CDKN2A and CDK4 status on the familial melanoma cases and clinical features associated with mutational status were then used to build a multiple logistic regression model to predict carrier probability and performance of model on external validation. Results: From the 116 kindreds prone to melanoma in the Boston area, 13 CDKN2A mutation carriers were identified and 12 were subsequently used in the modeling. Proband age at diagnosis, number of proband primaries, and number of additional family primaries were most closely associated with germline mutations. The estimated probability of the proband being a mutation carrier based on the logistic regression model (MELPREDICT) is given by e(L)/1+e(L) where L = 1.99+[0.926(no. of proband primaries)]+[0.74x(no.of additional family primaries)]-[2.11xIn((age))]. The mean estimated probabilities for subjects in the Boston dataset were 55.4% and 5.1% for the mutation carriers and non-carriers respectively. In a receiver operator characteristic analysis, the area under the curve was 0.881 (95% confidence interval 0.739 to 1.000) for the Boston model set (n = 116) and 0.803 (0.729 to 0.877) for an external Toronto hereditary melanoma cohort (n = 143). Conclusions: These results represent the first-iteration logistic regression model to approximate CDKN2A carrier probability. Validation of this model with an external dataset revealed relatively robust performance. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Risk Anal, Ctr Canc, Boston, MA 02114 USA. Chinese Univ Hong Kong, Ctr Biostat & Epidemiol, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org NR 24 TC 17 Z9 17 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUN PY 2006 VL 43 IS 6 BP 501 EP 506 DI 10.1136/jmg.2005.032441 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 048UZ UT WOS:000237973300006 PM 16169933 ER PT J AU Wambaugh, JL Duffy, JR McNeil, MR Robin, DA Rogers, MA AF Wambaugh, JL Duffy, JR McNeil, MR Robin, DA Rogers, MA TI Treatment guidelines for acquired apraxia of speech: A synthesis and evaluation of the evidence SO JOURNAL OF MEDICAL SPEECH-LANGUAGE PATHOLOGY LA English DT Article ID SOUND PRODUCTION TREATMENT; PERCEPTUAL CHARACTERISTICS; CONSONANT PRODUCTION; DYSARTHRIC SPEAKERS; APHASIA; THERAPY; OVERGENERALIZATION; VARIABILITY; CONSISTENCY; PATTERNS AB This report provides a summary and critical appraisal of the evidence utilized in the development of treatment guidelines for acquired apraxia of speech (AOS). This systematic review of the AOS treatment literature is a result of the efforts of the Academy of Neurologic Communication Disorders and Sciences (ANCDS) Writing Committee of Treatment Guidelines for AOS. Fifty-nine publications that met inclusion criteria were reviewed in terms of 33 variables pertaining to issues such as subject, treatment, and outcome descriptions, and scientific adequacy. Although the review revealed many weaknesses in the evidence base, findings indicated that patients with AOS can benefit from treatment. C1 VA Salt Lake City Healthcare Syst, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. Mayo Clin, Rochester, MN USA. Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. San Diego State Univ, San Diego, CA 92182 USA. Univ Washington, Seattle, WA 98195 USA. RP Wambaugh, JL (reprint author), 500 Foothill Blvd, Salt Lake City, UT 84148 USA. EM Julie.wambaugh@health.utah.edu RI Robin, Donald/F-2109-2010 NR 93 TC 59 Z9 60 U1 3 U2 21 PU DELMAR LEARNING PI CLIFTON PARK PA EXECUTIVE WOODS, 5 MAXWELL DR, CLIFTON PARK, NY 12065 USA SN 1065-1438 J9 J MED SPEECH-LANG PA JI J. Med. Speech-Lang. Pathol. PD JUN PY 2006 VL 14 IS 2 BP XV EP XXXIII PG 19 WC Audiology & Speech-Language Pathology; Clinical Neurology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology GA 047ME UT WOS:000237882600004 ER PT J AU Wambaugh, JL Duffy, JR McNeil, MR Robin, DA Rogers, MA AF Wambaugh, JL Duffy, JR McNeil, MR Robin, DA Rogers, MA TI Treatment guidelines for acquired apraxia of speech: Treatment descriptions and recommendations SO JOURNAL OF MEDICAL SPEECH-LANGUAGE PATHOLOGY LA English DT Article ID SOUND PRODUCTION TREATMENT; APHASIA; THERAPY; OVERGENERALIZATION; STIMULATION; ACCURACY; SPEAKER; ADULTS AB This article is the second of two reports from the Academy of Neurologic Communication Disorders and Sciences (ANCDS) Writing Committee of Treatment Guidelines for AOS. The first report provided a review and evaluation of the AOS treatment evidence (Wambaugh, Duffy, McNeil, Robin, & Rogers, 2006a). The current report is focused on the aspects of guidelines development that followed the review of the evidence. The major categories of AOS treatments are described in terms of treatment techniques, targets, outcomes, candidacy, and evidence quality. In addition, this report provides the committee's treatment recommendations and suggestions for future research. C1 VA Salt Lake City Healthcare Syst, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. Mayo Clin, Rochester, MN USA. Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. San Diego State Univ, San Diego, CA 92182 USA. Univ Washington, Seattle, WA 98195 USA. RP Wambaugh, JL (reprint author), 500 Foothill Blvd, Salt Lake City, UT 84148 USA. EM Julie.wambaugh@health.utah.edu RI Robin, Donald/F-2109-2010 NR 83 TC 22 Z9 23 U1 0 U2 18 PU DELMAR LEARNING PI CLIFTON PARK PA EXECUTIVE WOODS, 5 MAXWELL DR, CLIFTON PARK, NY 12065 USA SN 1065-1438 J9 J MED SPEECH-LANG PA JI J. Med. Speech-Lang. Pathol. PD JUN PY 2006 VL 14 IS 2 BP XXXV EP LXVII PG 33 WC Audiology & Speech-Language Pathology; Clinical Neurology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology GA 047ME UT WOS:000237882600005 ER PT J AU McCully, JD Rousou, AJ Levitsky, S AF McCully, J. D. Rousou, A. J. Levitsky, S. TI Differential age and gender response to ischemia: Efficacy of cardioprotection and the opening of mitoKATP channels SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 28th Annual International-Society-for-Heart-Research North American Section Meeting CY JUN 13-16, 2006 CL Toronto, CANADA SP Int Soc Heart Res, N Amer Sect C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2006 VL 40 IS 6 BP 887 EP 887 DI 10.1016/j.yjmcc.2006.03.350 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 053KR UT WOS:000238304500082 ER PT J AU Quinones, MP Jimenez, F Martinez, H Estrada, CA Willmon, O Dudley, M Kuziel, WA Melby, PC Reddick, RL Ahuja, SK Ahuja, SS AF Quinones, MP Jimenez, F Martinez, H Estrada, CA Willmon, O Dudley, M Kuziel, WA Melby, PC Reddick, RL Ahuja, SK Ahuja, SS TI CC chemokine receptor (CCR)-2 prevents arthritis development following infection by Mycobacterium avium SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; HEAT-SHOCK PROTEIN; BEIGE MOUSE MODEL; RHEUMATOID-ARTHRITIS; MOLECULAR MIMICRY; PONCETS-DISEASE; T-CELLS; NONTUBERCULOUS MYCOBACTERIA; INTRACELLULARE INFECTION; SEPTIC ARTHRITIS AB The host factors that influence autoimmune arthritides such as rheumatoid arthritis have not been fully elucidated. We previously found that genetic inactivation of CC chemokine receptor 2 (CCR2) in the arthritis-prone DBA/1j mouse strain significantly increases the susceptibility of this strain to autoimmune arthritis induced by immunization with collagen type II (CII) and complete Freund's adjuvant (CFA). Here, we show that following intradermal infection with Mycobacterium avium, a similar arthritis phenotype was detected in Ccr2-null mice in the DBA/1j, but not in the BALB/c background. The failure to develop arthritis in Ccr2-null BALB/c mice occurred in the face of high bacterial burdens and low interferon gamma (IFN gamma) production. By contrast, Ccr2-null DBA/1j mice had low bacterial burdens, produced normal amounts of IFN gamma, and had high titers of autoantibodies against CII. Thus, the Ccr2-null state in an arthritic-prone genetic background leads to increased arthritis susceptibility following infectious (M. avium) and noninfectious (CII/CFA) challenges. Because CCR2 serves as a negative regulator of murine arthritis, caution might need to be exercised while testing CCR2 blockers in human arthritis or other diseases. These findings also indicate that Ccr2-null DBA/1j mice might serve as a valuable model system to uncover the immunological determinants of arthritis and to test novel antiarthritic agents. C1 Univ Texas, Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. Prot Design Labs Inc, Fremont, CA 94555 USA. S Texas Vet Hlth Care Syst Audie L Murphy Div, San Antonio, TX USA. Vet Adm Ctr Res AIDS & HIV 1 Infect, San Antonio, TX USA. RP Ahuja, SS (reprint author), Univ Texas, Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr,MC 7870, San Antonio, TX 78229 USA. EM ahuja@uthscsa.edu FU NIAID NIH HHS [AI48644] NR 55 TC 8 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD JUN PY 2006 VL 84 IS 6 BP 503 EP 512 DI 10.1007/s00109-006-0039-3 PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 048RO UT WOS:000237964400007 PM 16520943 ER PT J AU Gonzalez, RG Greco, JB He, JL Lentz, MR O'Neil, S Pilkenton, SJ Ratai, EM Westmoreland, S AF Gonzalez, R. Gilberto Greco, Jane B. He, Julian Lentz, Margaret R. O'Neil, Shawn Pilkenton, Sarah J. Ratai, Eva M. Westmoreland, Susan TI New Insights into the Neuroimmunity of SIV Infection by Magnetic Resonance Spectroscopy SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Review DE MR spectroscopy; neuroAIDS; Simian immunodeficiency virus (SIV); CD8 T lymphocyte; Highly active antiretroviral therapy (HAART); N-acetylaspartate (NAA); AIDS; SIV encephalitis; Monocytes; CNS; Macrophages; HIV-associated dementia AB (1)H magnetic resonance spectroscopy (MRS) was employed to noninvasively monitor neuronal injury in eight rhesus macaques infected with simian immunodeficiency virus (SIV), whose immune system was compromised by CD8 T lymphocyte depletion and treated with highly active antiretroviral therapy ( HAART). SIV infection and CD8 depletion resulted in a rapid decline in cerebral N-acetylaspartate (NAA) levels, a sensitive marker of neuronal health. Within 3 months of SIV infection and CD8 depletion, four animals developed AIDS and severe SIV encephalitis. The other four macaques underwent daily doses of HAART beginning 4 weeks after infection/CD8 depletion. HAART involved drugs that do not penetrate the central nervous system (CNS) including 9-[2(R)-(phosphonomethoxy)propyl] adenine and a racemic mixture of D-L-enantiomers of 2',3'-dideoxy-5-fluoro-3'thiacytidine. HAART resulted in reversal of NAA/Cr decline after 4 weeks of therapy, and no virus or encephalitis was found in brain samples analyzed. These results indicate that the CNS injury in AIDS is entirely dependent on events involving the peripheral immune system mediated by trafficking of SIV-infected monocytes into the brain. The rapid decline in NAA/Cr with SIV infection/CD8 depletion and its rapid recovery with HAART suggest that: ( 1) infected monocyte turnover in the CNS is rapid, occurring in days to weeks; ( 2) there are endogenous mechanisms that reverse neuronal injury; and ( 3) a threshold level of infected monocytes/macrophages in the CNS is required to overcome the neuronal recovery processes. These observations explain the clinical success of antiretroviral therapy in reducing the incidence of HIV-associated dementia and minor cognitive/motor disorder and suggest novel targets for drug development. C1 [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. [Gonzalez, R. Gilberto; Greco, Jane B.; He, Julian; Lentz, Margaret R.; O'Neil, Shawn; Pilkenton, Sarah J.; Ratai, Eva M.; Westmoreland, Susan] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gonzalez, R. Gilberto; Greco, Jane B.; He, Julian; Lentz, Margaret R.; Pilkenton, Sarah J.; Ratai, Eva M.] Massachusetts Gen Hosp, Neuroradiol Div, Charlestown, MA 02129 USA. [Gonzalez, R. Gilberto; Greco, Jane B.; He, Julian; Lentz, Margaret R.; Pilkenton, Sarah J.; Ratai, Eva M.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [O'Neil, Shawn] New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Westmoreland, Susan] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA 02129 USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,55 Fruit St, Boston, MA 02114 USA. EM rggonzalez@partners.org FU NIH; National Center for Research Resources (NCRR) [RR13214, RR000150, RR00168]; National Institute of Allergy and Infectious Diseases [AI028691]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery Institute; National Institute of Neurological Diseases and Stroke [NS34626, NS0050041]; National Cell Culture Center with funds provided by NCRR [RR16001, RR14075] FX This work was supported in part by grants from the NIH, including National Center for Research Resources (NCRR) RR13214 (to R. G. Gonzalez) and RR000150 and RR00168 ( to New England Primate Research Center); National Institute of Allergy and Infectious Diseases AI028691 (to E. Ratai), P41RR14075 ( National Center for Research Resources grant), Mental Illness and Neuroscience Discovery Institute; National Institute of Neurological Diseases and Stroke NS34626 and NS0050041 ( to R. G. Gonzalez). The CD8 Tlymphocyte- depleting mAb used in this work was produced by the National Cell Culture Center with funds provided by NCRR grant RR16001. The Center for Functional Imaging Technologies at the Massachusetts General Hospital is supported by NCRR grant RR14075. NR 55 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD JUN PY 2006 VL 1 IS 2 BP 152 EP 159 DI 10.1007/s11481-006-9016-4 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA V04MV UT WOS:000207063400004 PM 18040781 ER PT J AU Jha, S Xu, KP Maruta, T Oshima, M Mosier, DR Atassi, MZ Hoch, W AF Jha, S Xu, KP Maruta, T Oshima, M Mosier, DR Atassi, MZ Hoch, W TI Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK) SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE antibodies; autoimmunity; muscle-specific kinase; myasthenia gravis; mouse model; agrin ID T-CELL RECOGNITION; ACETYLCHOLINE-RECEPTOR; NEUROMUSCULAR-JUNCTION; ANTI-TITIN; TYROSINE PHOSPHORYLATION; IMMUNE RESPONSIVENESS; SYNAPSE FORMATION; SKELETAL-MUSCLE; SERONEGATIVE MG; GENETIC-CONTROL AB Myasthenia gravis (MG) is mostly caused by anti-acetylcholine receptor (AChR) auto-antibodies (Abs). Such Abs are undetectable in 10-15% of MG patients, but many have anti-muscle-specific kinase (MuSK) Abs. We injected recombinant rat-MuSK extracellular domain in H-2(a), H-2(b), H-2(bm12) and H-2(d) mice. Certain strains exhibited exercise-induced fatigue, tremors, weight loss, and some died after 2-3 injections. Compound muscle action potentials showed decrement with low-frequency repetitive nerve stimulation. Miniature endplate potentials decreased, suggesting lower numbers of endplates functional AChRs. Myasthenic sera inhibited agrin-induced AChR aggregation in C2C12 myotubes. Conclusion: Anti-MuSK Abs induce MG, which might also result from blocking the agrin-signaling pathway. (c) 2006 Published by Elsevier B.V C1 Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA. Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. ME DeBakey Vet Affairs Med Ctr, Neurol & Med Res Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. RP Atassi, MZ (reprint author), Baylor Coll Med, Dept Biochem & Mol Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM matassi@bcm.edu NR 46 TC 63 Z9 66 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUN PY 2006 VL 175 IS 1-2 BP 107 EP 117 DI 10.1016/j.jneuroim.2006.03.016 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 056HA UT WOS:000238511600012 PM 16697051 ER PT J AU Weintraub, D Taraborelli, D Morales, KH Duda, JE Katz, IR Stern, MB AF Weintraub, Daniel Taraborelli, Donna Morales, Knashawn H. Duda, John E. Katz, Ira R. Stern, Matthew B. TI Escitalopram for major depression in Parkinson's disease: An open-label, flexible-dosage study SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID PLACEBO-CONTROLLED TRIAL; SYMPTOMATOLOGY IDS; PAROXETINE; CITALOPRAM; SERTRALINE; ANXIETY; NORTRIPTYLINE; COMORBIDITY; INVENTORY; DOPAMINE AB Depression and antidepressant use are common in Parkinson's disease, but the benefit of selective serotonin reuptake inhibitor (SSRI) treatment in this population has not been established. The authors treated 14 Parkinson's disease patients with major depression with escitalopram in an open-label study. Although treatment was well tolerated and correlated with a significant decrease in Inventory of Depressive Symptomatology score, response and remission rates were only 21% and 14%, respectively. However, half of the subjects met Clinical Global Impression-Improvement criteria for response. In Parkinson's disease, either SSRIs may have limited antidepressant effects, or the use of existing depression diagnostic and rating instruments may be problematic. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Weintraub, D (reprint author), 3535 Market St,Rm 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [K23 MH067894] NR 44 TC 27 Z9 27 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 2006 VL 18 IS 3 BP 377 EP 383 DI 10.1176/appi.neuropsych.18.3.377 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 081AC UT WOS:000240288600009 PM 16963587 ER PT J AU McMurtray, AM Clark, DG Flood, MK Perlman, S Mendez, MF AF McMurtray, Aaron M. Clark, David G. Flood, Mary K. Perlman, Susan Mendez, Mario F. TI Depressive and memory symptoms as presenting features of spinocerebellar ataxia SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID OLIVOPONTOCEREBELLAR ATROPHY; DEGENERATION AB The spinocerebellar ataxias (SCA) can be manifested in neuropsychiatric symptoms. Among 76 SCA patients presenting to a university ataxia center, depressive symptoms characterized SCA3. Memory symptoms occurred across all SCA groups with relative sparing of SCA6. These differences in neuropsychiatric symptoms suggest the subtype of SCA and the corresponding neuropathological involvement. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP McMurtray, AM (reprint author), Vet Affairs Greater Los Angeles Healthcare, 166AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM aaronmnm@hawaii.edu FU NINDS NIH HHS [R01-NS33123] NR 9 TC 16 Z9 18 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 2006 VL 18 IS 3 BP 420 EP 422 DI 10.1176/appi.neuropsych.18.3.420 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 081AC UT WOS:000240288600017 PM 16963595 ER PT J AU Panizzon, K Allen, S Wallis, RA AF Panizzon, Kimberly Allen, Suni Wallis, Roi Ann TI Modulation of the mitochondrial ATP-sensitive potassium channel by diazoxide provides protection against neuronal injury induced by trauma to cortical slices SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 24th Annual National-Neurotrauma-Society Symposium CY JUL 07-09, 2006 CL St Louis, MO SP Natl Neurotrauma Soc C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 2006 VL 23 IS 6 MA P151 BP 1025 EP 1025 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 056TW UT WOS:000238549000162 ER PT J AU Wallis, RA Panizzon, K AF Wallis, Roi Ann Panizzon, Kimberly TI Pravastatin provides protection against CA1 traumatic neuronal injury SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 24th Annual National-Neurotrauma-Society Symposium CY JUL 07-09, 2006 CL St Louis, MO SP Natl Neurotrauma Soc C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 2006 VL 23 IS 6 MA P193 BP 1036 EP 1036 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 056TW UT WOS:000238549000203 ER PT J AU Shankar, LK Hoffman, JM Bacharach, S Graham, MM Karp, J Lammertsma, AA Larson, S Mankoff, DA Siegel, BA den Abbeele, A Yap, J Sullivan, D AF Shankar, LK Hoffman, JM Bacharach, S Graham, MM Karp, J Lammertsma, AA Larson, S Mankoff, DA Siegel, BA den Abbeele, A Yap, J Sullivan, D TI Consensus recommendations for the use of F-18-FDG PET as an indicator of therapeutic response in patients in national cancer institute trials SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; STANDARDIZED UPTAKE VALUE; BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; FDG-PET; GRAPHICAL EVALUATION; FLOW-CYTOMETRY; BREAST-CANCER; SERUM GLUCOSE; LUNG-CANCER C1 NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA. Univ Utah, Sch Med, Huntsman Canc Inst, Div Nucl Med, Salt Lake City, UT USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Iowa, Dept Radiol, Div Nucl Med, Iowa City, IA 52242 USA. Univ Penn, Dept Radiol, Div Nucl Med, Philadelphia, PA 19104 USA. Vrije Univ Amsterdam, Dept Nucl Med & PET Res, NL-1081 HV Amsterdam, Netherlands. Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. Univ Washington, Div Nucl Med, Seattle, WA 98195 USA. Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Shankar, LK (reprint author), NCI, Canc Imaging Program, NIH, 6130 Execut Blvd,Room 6048, Bethesda, MD 20892 USA. EM shankarl@mail.nih.gov RI Mankoff, David/F-9576-2010 NR 32 TC 416 Z9 429 U1 2 U2 9 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUN PY 2006 VL 47 IS 6 BP 1059 EP 1066 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 050RE UT WOS:000238104800028 PM 16741317 ER PT J AU Goudreau, KA Hardy, J AF Goudreau, KA Hardy, J TI Succession planning and individual development SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article AB The authors present a framework for a succession planning and individual development initiative implemented in a Veterans Health Administration facility. Foundational strategic goals and a conceptual framework in the Veterans Affairs system provide the structure for the 3 facility-level succession planning and individual development programs. Outcomes of the programs are promising with 2 of 3 programs demonstrating clear succession planning outcomes and the other one showing positive preliminary results. C1 Portland VA Med Ctr, P3EDUC, Portland, OR 97239 USA. RP Goudreau, KA (reprint author), Portland VA Med Ctr, P3EDUC, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM kagoudreau@hotmail.com NR 10 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUN PY 2006 VL 36 IS 6 BP 313 EP 318 DI 10.1097/00005110-200606000-00007 PG 6 WC Nursing SC Nursing GA 054II UT WOS:000238369600006 PM 16766911 ER PT J AU Ponte, PR Gross, AH Galante, A Glazer, G AF Ponte, PR Gross, AH Galante, A Glazer, G TI Using an executive coach to increase leadership effectiveness SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article AB Senior executive nursing roles demand excellence and rigor in both the technical and interpersonal domains of leadership. Many nurse leaders have begun seeking innovative self-development programs and practices to assist them as they strive to improve their effectiveness as leaders in complex organizations. One practice that has gained in popularity is that of engaging a leadership "coach." To understand this relatively new trend in health-care leadership, the authors interviewed 4 coaches and 4 nurse leaders who had been coached. In this article, they present their overall findings about the effectiveness of coaching as a leadership development tool and offer recommendations for leaders who are interested in engaging a coach. C1 Dana Farber Canc Inst, Adult Ambulatory Serv, Boston, MA 02115 USA. Brigham & Womens Hosp, Oncol Nursing & Clin Serv, Boston, MA 02115 USA. Brigham & Womens Hosp, Hematol Oncol & Bone Marrow Transplant, Boston, MA 02115 USA. Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. RP Ponte, PR (reprint author), Dana Farber Canc Inst, Nursing & Patient Care Serv, 44 Binney St, Boston, MA 02115 USA. EM pat_reid_ponte@dfci.harvard.edu NR 14 TC 5 Z9 5 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUN PY 2006 VL 36 IS 6 BP 319 EP 324 PG 6 WC Nursing SC Nursing GA 054II UT WOS:000238369600007 PM 16766912 ER PT J AU Baeten, JM Wener, MH Bankson, DD Lavreys, L Richardson, BA Mandaliya, K Bwayo, JJ McClelland, RS AF Baeten, JM Wener, MH Bankson, DD Lavreys, L Richardson, BA Mandaliya, K Bwayo, JJ McClelland, RS TI HIV-1 infection alters the retinol-binding protein : transthyretin ratio even in the absence of the acute phase responsel SO JOURNAL OF NUTRITION LA English DT Article DE vitamin A status; retinol-binding protein; transthyretin; HIV; inflammation ID VITAMIN-A STATUS; SERUM RETINOL; MOLAR RATIO; DEFICIENCY; PLASMA; CHILDREN; WOMEN; RBP; TTR AB The ratio of retinol-binding protein (RBP) to transthyretin (TTR) has been proposed as an indirect method with which to assess vitamin A status in the context of inflammation. Few studies have been conducted among adults, and none examined the effect of HIV-1 infection. Our goal was to assess the RBP:TTR ratio among adults, including the effects of HIV-1 and the acute phase response. We used data from a cross-sectional study of 600 Kenyan women, of whom 400 had HIV-1. The effect of vitamin A supplementation among the HIV-1-infected participants was subsequently assessed in a randomized trial. Among HIV-1-uninfected women without an acute phase response, a RBP:TTR cut-off value of 0.25 had similar to 80% sensitivity and specificity to detect vitamin A deficiency (retinol < 0.70 mu mol/L). No RBP:TTR cut-off value demonstrated both high sensitivity and specificity among HIV-1 infected women without evidence of inflammation. HIV-1 infection and advanced HIV-1 disease were associated with higher RBP:TTR ratios. The effect of HIV-1 was independent of the acute phase response, which also increased the RBP:TTR ratio. Serum retinol increased with vitamin A supplementation among those with a low RBP:TTR ratio, although the effect was small and was not present among those with concurrent inflammation. Thus, the RBP:TTR ratio has modest ability to predict vitamin A deficiency among healthy adults, but HIV-1 infection alters the ratio, even in the absence of the acute phase response. Our results raise questions about the utility of this measurement given the high prevalence of HIV-1 infection in areas where vitamin A deficiency is common. C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Coast Prov Gen Hosp, Mombasa, Kenya. Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya. RP Baeten, JM (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM jbaeten@u.washington.edu FU FIC NIH HHS [D43-TW00007]; NIAID NIH HHS [AI43844, AI39996]; NIDDK NIH HHS [DK35816] NR 19 TC 5 Z9 5 U1 0 U2 1 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUN PY 2006 VL 136 IS 6 BP 1624 EP 1629 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 046SV UT WOS:000237832200030 PM 16702331 ER PT J AU Cohen, SP Verdolin, MH Chang, AS Kurihara, C Morlando, BJ Mao, JR AF Cohen, SP Verdolin, MH Chang, AS Kurihara, C Morlando, BJ Mao, JR TI The intravenous ketamine test predicts subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients SO JOURNAL OF PAIN LA English DT Article DE dextromethorphan; fibromyalgia; ketamine; N-methyl-D-aspartate receptor antagonist; intravenous infusion test ID ASPARTATE RECEPTOR ANTAGONISTS; PAINFUL DIABETIC NEUROPATHY; DOUBLE-BLIND; POSTOPERATIVE PAIN; TEMPORAL SUMMATION; POSTHERPETIC NEURALGIA; ANALGESIA; MULTICENTER; LIDOCAINE; PLACEBO AB Fibromyalgia (FM) is a challenging pain syndrome for which no reliable pharmacologic treatment exists. Recent clinical studies suggest that N-methyl-D-aspartate receptors might play a role in the pathogenesis of this disorder. To determine whether an intravenous (IV) ketamine test predicts the response to a therapeutic trial with an oral N-methyl-D-aspartate receptor antagonist, we performed a low-dose (0.1 mg/kg) IV ketamine infusion on 34 consecutive patients with FM, which was subsequently followed by an oral dextromethorphan (DX) treatment regimen. As per previous guidelines, the cutoff value for a positive response to the IV ketamine test was designated to be 67% pain relief, and a positive response to DX treatment was 50% pain reduction at 4- to 6-week follow-up visits. The degree of correlation between pain relief with ketamine and DX was highly significant (Pearson correlation coefficient, 0.66; P <.001). Ten patients responded positively to both ketamine and DX, 19 responded to neither drug, 3 had a positive response to ketamine but not DX, and 2 obtained good pain relief with DX but not ketamine. The sensitivity of the IV ketamine test was 83%, the specificity was 86%, the positive predictive value was 77%, and the negative predictive value was 91 %. An association was also found between the development of side effects to the two treatments. Perspective: The response to an IV ketamine infusion was found to predict the subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients, with an observed agreement of 83 %. Considering the refractory nature of fibromyalgia to conventional pain treatments, the lV ketamine test might enhance patient care by saving time and reducing unnecessary treatment trials. (C) 2006 by the American Pain Society. C1 Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Pain Management Div, Baltimore, MD 21205 USA. Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Clin Invest, Clin Studies Div, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Pain Treatment Ctr, Washington, DC 20307 USA. Naval Med Ctr San Diego, Pain Treatment Ctr, San Diego, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Pain Management Ctr, Boston, MA USA. RP Cohen, SP (reprint author), Johns Hopkins Sch Med, Dept Anesthesiol & Crit Care Med, Pain Management Div, 550 N Broadway,Suite 301, Baltimore, MD 21205 USA. EM scohen40@jhmi.edu NR 31 TC 22 Z9 22 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD JUN PY 2006 VL 7 IS 6 BP 391 EP 398 DI 10.1016/j.jpain.2005.12.010 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 053WZ UT WOS:000238338100002 PM 16750795 ER PT J AU Goy, ER Carlson, B Simopoulos, N Jackson, A Ganzini, L AF Goy, ER Carlson, B Simopoulos, N Jackson, A Ganzini, L TI Determinants of oregon hospice chaplains' views on physician-assisted suicide SO JOURNAL OF PALLIATIVE CARE LA English DT Article ID DIGNITY ACT; SOCIAL-WORKERS; ATTITUDES; EXPERIENCES; DEATH; CARE; PSYCHIATRISTS; NURSES AB Background: Although religiousness is a strong predictor of attitudes towards physician-assisted suicide (PAS), Oregon hospice chaplains express wide variation in their opposition to or support for legalized PAS. We explored factors associated with chaplains' views on PAS. Methods: A mailed survey to chaplains from 51 Oregon hospices. Results: Fifty of 77 eligible hospice chaplains (65%) returned surveys. Views on PAS were associated with views on suicide in general. Moral and theological beliefs were the most important influences on views on PAS. Chaplains who were opposed to PAS believed that God alone may take life, that life is an absolute good, and that suffering has a divine purpose. Those who supported PAS placed emphasis on the importance of self-determination and sanctity of life as defined by quality of life. Conclusions: Oregon hospice chaplains' diverse views towards PAS are closely related to their views on suicide in general, and their personal and theological beliefs. C1 Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Episcopal Sch, Portland, OR USA. Oregon Hospice Assoc, Portland, OR USA. RP Goy, ER (reprint author), Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU CENTER BIOETHICS CLIN RES INST MONTREAL PI MONTREAL PA 110 PINE AVE W, MONTREAL, QUEBEC H2W 1R7, CANADA SN 0825-8597 J9 J PALLIATIVE CARE JI J. Palliative Care PD SUM PY 2006 VL 22 IS 2 BP 83 EP 90 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 058PC UT WOS:000238675900004 PM 17265660 ER PT J AU Tarakeshwar, N Vanderwerker, LC Paulk, E Pearce, MJ Kasl, SV Prigerson, HG AF Tarakeshwar, N Vanderwerker, LC Paulk, E Pearce, MJ Kasl, SV Prigerson, HG TI Religious coping is associated with the quality of life of patients with advanced cancer SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID TERMINALLY-ILL; SPIRITUALITY; HEALTH; CARE; QUESTIONNAIRE; DIMENSIONS; DEPRESSION; PATTERNS; OUTCOMES; AMERICA AB Background: For patients confronting a life-threatening illness such as advanced cancer, religious coping can be an important factor influencing their quality of life QOL). Objective: The study's main purpose was to examine the association between religious coping and QOL among 170 patients with advanced cancer. Both positive religious coping (e.g., benevolent religious appraisals) and negative religious coping (e.g., anger at God) and multiple dimensions of QOL (physical, physical symptom, psychological, existential, and support) were studied. Design: Structured interviews were conducted with 170 patients recruited as part of an ongoing multi-institutional longitudinal evaluation of the prevalence of mental illness and patterns of mental health service utilization in advanced cancer patients and their primary informal caregivers. Measurements: Patients completed measures of QOL (McGill QOL questionnaire), religious coping (Brief Measure of Religious Coping [RCOPE] and Multidimensional Measure of Religion/Spirituality), self-efficacy (General Self-Efficacy Scale), and sociodemographic variables. Results: Linear regression analyses revealed that after controlling for sociodemographic variables, lifetime history of depression and self-efficacy, greater use of positive religious coping was associated with better overall QOL as well as higher scores on the existential and support QOL dimensions. Greater use of positive religious coping was also related to more physical symptoms. In contrast, greater use of negative religious coping was related to poorer overall QOL and lower scores on the existential and psychological QOL dimensions. Conclusions: Findings show that religious coping plays an important role for the QOL of patients and the types of religious coping strategies used are related to better or poorer QOL. C1 Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Palliat Care Serv, Dallas, TX USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Suite 440ASW,44 Binney St, Boston, MA 02115 USA. EM Holly_Prigerson@dfci.harvard.edu FU FIC NIH HHS [K01 TW007136, K01 TW007136-01]; NCI NIH HHS [R01 CA106370, CA106370, R01 CA106370-01]; NIA NIH HHS [P30 AG021342, P30AG21342]; NIMH NIH HHS [MH-56529, MH63892, R01 MH063892] NR 53 TC 129 Z9 130 U1 3 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2006 VL 9 IS 3 BP 646 EP 657 DI 10.1089/jpm.2006.9.646 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 052OK UT WOS:000238242800010 PM 16752970 ER PT J AU Lorenz, KA Shugarman, LR Lynn, J AF Lorenz, KA Shugarman, LR Lynn, J TI Health care policy issues in end-of-life care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID CONGESTIVE-HEART-FAILURE; OBSTRUCTIVE PULMONARY-DISEASE; TERMINAL CANCER-PATIENTS; HOME-BASED INTERVENTION; LAST 6 MONTHS; NATIONAL HOSPICE; MEDICARE EXPENDITURES; PAIN MANAGEMENT; DEPRESSIVE SYMPTOMS; REGIONAL-VARIATIONS C1 VA Greater Los Angeles Healthcare Syst, Vet Integrated Palliat Program, Div Gen Internal Med, Los Angeles, CA 90073 USA. Rand Hlth, Santa Monica, CA USA. Rand Hlth, Arlington, VA USA. RP Lorenz, KA (reprint author), VA Greater Los Angeles Healthcare Syst, Vet Integrated Palliat Program, Div Gen Internal Med, 11301 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. EM karl.lorenz@med.va.gov NR 141 TC 15 Z9 15 U1 4 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2006 VL 9 IS 3 BP 731 EP 748 DI 10.1089/jpm.2006.9.731 PG 18 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 052OK UT WOS:000238242800019 PM 16752979 ER PT J AU Block, SD AF Block, SD TI Psychological issues in end-of-life care SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review ID METASTATIC BREAST-CANCER; BORDERLINE PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; GROUP PSYCHOSOCIAL SUPPORT; CONGESTIVE-HEART-FAILURE; PLACEBO-CONTROLLED TRIAL; TERMINALLY-ILL PATIENTS; BRAIN-TUMOR PATIENTS; PALLIATIVE CARE AB This paper provides a systematic, evidence-based review of the psychological issues confronted by patients at the end of life, drawing on recent literature. The epidemiology, approach to clinical assessment, clinical presentation, and therapeutic options related to common psychological issues that arise in end-stage illness are described. The spectrum of normal and dysfunctional reactions are identified, and approaches to enhancing coping and quality of life are emphasized. The learner will be able to describe: (1) normal coping responses of patients at the end of life; (2) epidemiology of common psychiatric disorders at the end of life; (3) the approach to clinical assessment of psychological distress at the end of life; and (4) therapeutic approaches to common psychological problems at the end of life. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Psychosocial Oncol & Pallait Care, Dana Farber Canc Inst,Ctr Palliat Care, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Block, SD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Psychosocial Oncol & Pallait Care, Dana Farber Canc Inst,Ctr Palliat Care, 44 Binney St, Boston, MA 02115 USA. EM sblock@partners.org NR 173 TC 45 Z9 45 U1 4 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2006 VL 9 IS 3 BP 751 EP 772 DI 10.1089/jpm.2006.9.751 PG 22 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 052OK UT WOS:000238242800021 PM 16752981 ER PT J AU Wolfe, J AF Wolfe, J TI Withholding or withdrawing care in newborns SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Wolfe, J (reprint author), Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2006 VL 9 IS 3 BP 820 EP 820 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 052OK UT WOS:000238242800033 ER PT J AU Senkal, CE Ponnusamy, S Rossi, MJ Sundararaj, K Szulc, Z Bielawski, J Bielawska, A Meyer, M Cobanoglu, B Koybasi, S Sinha, D Day, TA Obeid, LM Hannun, YA Ogretmen, B AF Senkal, CE Ponnusamy, S Rossi, MJ Sundararaj, K Szulc, Z Bielawski, J Bielawska, A Meyer, M Cobanoglu, B Koybasi, S Sinha, D Day, TA Obeid, LM Hannun, YA Ogretmen, B TI Potent antitumor activity of a novel cationic pyridinium-ceramide alone or in combination with gemcitabine against human head and neck squamous cell carcinomas in vitro and in vivo SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TELOMERE LENGTH; BREAST-CANCER; PHASE-II; TUMOR; CHEMOTHERAPY; CISPLATIN; APOPTOSIS; MITOCHONDRIA; INHIBITION; DELIVERY AB In this study, a cationic water-soluble ceramide analog L-threo-C6-pyridinium-ceramide-bromide (L-t-C-6-Pyr-Cer), which exhibits high solubility and bioavailability, inhibited the growth of various human head and neck squamous cell carcinoma (HNSCC) cell lines at low IC50 concentrations, independent of their p53 status. Consistent with its design to target negatively charged intracellular compartments, L-t-C-6-Pyr-Cer accumulated mainly in mitochondria, and nuclei- enriched fractions upon treatment of human UM-SCC-22A cells [human squamous cell carcinoma (SCC) of the hypopharynx] at 1 to 6 h. In addition to its growth-inhibitory function as a single agent, the supra-additive interaction of L-t-C(6)Pyr-Cer with gemcitabine (GMZ), a chemotherapeutic agent used in HNSCC, was determined using isobologram studies. Then, the effects of this ceramide, alone or in combination with GMZ, on the growth of UM-SCC-22A xenografts in SCID mice was assessed following the determination of preclinical parameters, such as maximum tolerated dose, clearance from the blood, and bioaccumulation. Results demonstrated that treatment with L-t-C-6-Pyr-Cer in combination with GMZ significantly prevented the growth of HNSCC tumors in vivo. The therapeutic efficacy of L-t-C-6-Pyr-Cer/GMZ combination against HNSCC tumors was approximately 2.5-fold better than that of the combination of 5-fluorouracil/cisplatin. In addition, liquid chromatography/mass spectroscopy analysis showed that the levels of L-t-C-6-Pyr-Cer in HNSCC tumors were significantly higher than its levels in the liver and intestines; interestingly, the combination with GMZ increased the sustained accumulation of this ceramide by approximately 40%. Moreover, treatment with L-t-C-6-Pyr-Cer/GMZ combination resulted in a significant inhibition of telomerase activity and decrease in telomere length in vivo, which are among downstream targets of ceramide. C1 Med Univ S Carolina, Dept Biochem, Charleston, SC 29424 USA. Med Univ S Carolina, Dept Mol Biol, Charleston, SC 29424 USA. Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29424 USA. Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29424 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29424 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29424 USA. Med Univ S Carolina, Ralph H Johnson Vet Adm Hosp, Charleston, SC 29424 USA. RP Ogretmen, B (reprint author), Med Univ S Carolina, Dept Biochem, 173 Ashley Ave, Charleston, SC 29424 USA. EM ogretmen@musc.edu OI obeid, lina/0000-0002-0734-0847 NR 40 TC 53 Z9 54 U1 1 U2 5 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 2006 VL 317 IS 3 BP 1188 EP 1199 DI 10.1124/jpet.106.101949 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 044AE UT WOS:000237643600032 PM 16510697 ER PT J AU Fava, M Detke, MJ Balestrieri, M Wang, FJ Raskin, J Perahia, D AF Fava, M Detke, MJ Balestrieri, M Wang, FJ Raskin, J Perahia, D TI Management of depression relapse: Re-initiation of duloxetine treatment or dose increase SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE depression; relapse; duloxetine; long-term ID PRIMARY-CARE; DISORDER RELAPSE; ANTIDEPRESSANTS; SEROTONIN; THERAPY; VENLAFAXINE; FLUOXETINE; PREVENTION; STRATEGIES; REMISSION AB Continuation of antidepressant therapy after patients have responded to medication has been shown to greatly reduce but not eliminate relapse. We evaluated response to reinstating or increasing drug doses in patients who relapsed during a long-term, randomized, double-blind, continuation phase study of duloxetine treatment for major depressive disorder (MDD). Patients with HAMD(17) scores of > 18 and CGI-Severity scores of > 4 received duloxetine 60 mg QD for 12 weeks, responders then received 26 weeks of duloxetine 60 mg QD or placebo. The relapsing patients who started 12 weeks of rescue treatment received duloxetine 60 mg QD (if relapsing on placebo) or duloxetine 60 mg BID (if relapsing on duloxetine). In the continuation phase, 87 patients received duloxetine 60 mg QD (n = 58) or 60 mg BID (n = 29) as treatment for relapse. The percentage of patients who responded to treatment after relapse was 62% of those whose dose was increased from 60 mg QD to 60 mg BID, and 74% for those who switched from placebo to duloxetine 60 mg daily. By the end of the study, 32 patients taking duloxetine 60 mg QD were in remission (57%), compared with I I patients taking duloxetine 60 mg BID (38%). There was significant improvement in HAMD17 and CGI-Severity scores for both groups at endpoint vs. start of treatment for relapse. Significant improvements were seen for all visual analog scale parameters in the 60 mg QD group, but only Interference with Daily Activities and Back Pain parameters showed significant improvement for patients receiving 60 mg BID. Significant within-group improvement from baseline was seen for both groups in Symptom Questionnaire-Somatic Subscale total and pain subscales. Treatment-emergent adverse events were mild/moderate in severity; no clinically significant changes were noted in laboratory results or vital signs. Reinstatement of duloxetine 60 mg QD was effective for patients who relapsed after discontinuing drug. Patients relapsing on duloxetine 60 mg QD benefited from an increase to 60 mg BID. These duloxetine doses were well tolerated and effective, and appear appropriate for MDD patients requiring treatment of relapse. (c) 2005 Published by Elsevier Ltd. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Cambridge, MA 02140 USA. Lilly Res Labs, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46204 USA. McLean Hosp, Dept Psychiat, Belmont, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Udine, Dipartmento Patol & Med SC, Cattedra Psichiat, I-33100 Udine, Italy. Eli Lilly Canada, Toronto, ON, Canada. Lilly Res Ctr, Windlesham, Surrey, England. Gordon Hosp, London, England. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,ACC 812, Cambridge, MA 02140 USA. EM MFava@Partners.org NR 42 TC 11 Z9 11 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JUN PY 2006 VL 40 IS 4 BP 328 EP 336 DI 10.1016/j.jpsychires.2005.06.005 PG 9 WC Psychiatry SC Psychiatry GA 050TA UT WOS:000238110200007 PM 16678205 ER PT J AU Papakostas, GI Petersen, TJ Burns, AM Fava, M AF Papakostas, GI Petersen, TJ Burns, AM Fava, M TI Adjunctive atomoxetine for residual fatigue in major depressive disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE atomoxetine; adjunctive; fatigue; major depressive disorder ID MODAFINIL AUGMENTATION; DAYTIME SLEEPINESS; RATING-SCALE; FLUOXETINE; TERM AB Objective: To assess the effectiveness and safety of atomoxetine as an adjunctive medication for residual fatigue in a naturalistic treatment setting. Methods: A retrospective chart review was conducted to identify major depressive disorder (MDD) patients who had experienced significant symptom improvement (either partial response or remission) following treatment with conventional antidepressants but who were continuing to complain of fatigue. Fourteen such patients (42.2 +/- 13.4 years of age, five women, baseline HDRS 6.2 +/- 2.4) with a 17-item Hamilton Depression Rating Scale (HDRS 17) < 11 who received adjunctive atomoxetine for fatigue were included in the report. Antidepressants augmented were the selective serotonin reuptake inhibitors (SSRIs) (n = 11; 78.6%), mirtazapine (n = 2, 14.3%), and amitriptyline (n = 1, 7.1 %). Results: Twelve (85.7%) patients (nine remitters, three partial responders) received at least 4 weeks of atomoxetine treatment. The remaining two (partial responders) discontinued atomoxetine within 1-3 days due to increased anxiety. The brief fatigue inventory (BFI) and Clinical Global Impressions Scale (CGI) were administered when atomoxetine was first prescribed, and following 4-10 weeks of treatment (mean of 5.4 +/- 1.8 weeks). There was a significant decrease in BFI scores (41.9 +/- 14.9 versus 24.3 +/- 13.4, p = 0.0015), and HDRS-17 scores (6.2 +/- 2.4 versus 3.5 +/- 2.8, p = 0.0466), but not CGI-S scores (1.3 +/- 1.4-1.0 +/- 0.0, p = 0.08) following treatment with atomoxetine. 5/12 (41.6%) patients had a 50% or greater decrease in BFI scores. All 12 patients were remitters at follow-up. The mean atomoxetine dose was 42.8 +/- 10.6 mg. Side effects included insomnia (n = 6), increased anxiety (n = 3), nausea (n = 1) and dry mouth (n = 1). Conclusions: Although preliminary, these results suggest a possible augmentation role for atomoxetine when used in conjunction with conventional antidepressants for residual fatigue in MDD. Prospective as well as controlled studies are necessary to further explore the role of atomoxetine augmentation in MDD. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), 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 NR 21 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JUN PY 2006 VL 40 IS 4 BP 370 EP 373 DI 10.1016/j.jpsychires.2005.04.013 PG 4 WC Psychiatry SC Psychiatry GA 050TA UT WOS:000238110200012 PM 15978621 ER PT J AU Thompson, R Kane, V Cook, JM Greenstein, R Walker, P Woody, G AF Thompson, Richard Kane, Vincent Cook, Joan M. Greenstein, Robert Walker, Patricia Woody, George TI Suicidal ideation in veterans receiving treatment for opiate dependence SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE opiate; screening; suicide; veterans ID MEDICAL-CENTER; PRIMARY-CARE; LATE-LIFE; PATTERNS; RISK AB Persons with opiate use disorders, especially veterans, have a number of both chronic and acute indicators of risk for suicide, but are not typically screened for suicidal ideation on a routine basis, beyond initial evaluations. One hundred one veterans receiving treatment for opiate dependence at an urban VA medical center were screened for suicidal ideation. Over 24% reported some suicidal ideation. Current ideation was associated with severe chronic pain, ongoing problems with street drugs, firearm ownership, and with having recently enrolled in treatment. It was also associated with a variety of recent negative life events and mental health issues, especially depression, recurring troubling thoughts, hallucinations, loss of jobs, and conflicts with family members. Two veterans endorsing suicidal ideation required immediate hospitalization. The implications of these findings are discussed, and frequent screening for suicidal ideation among patients receiving treatment for opiate dependence is recommended. C1 Univ Illinois, Dept Psychiat, Juvenile Protect Assoc, Chicago, IL 60622 USA. Philadelphia VA Med Ctr, VISN 4 MIRECC, Philadelphia, PA USA. Philadelphia VA Med Ctr, Dept Behav Hlth, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Thompson, R (reprint author), Univ Illinois, Dept Psychiat, Juvenile Protect Assoc, 1333 N Kingbury,Suite 306, Chicago, IL 60622 USA. RI Thompson, Richard/G-5408-2011 OI Thompson, Richard/0000-0003-0127-513X NR 28 TC 5 Z9 5 U1 2 U2 2 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 2006 VL 38 IS 2 BP 149 EP 156 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 065XX UT WOS:000239194600005 PM 16903454 ER PT J AU Cadge, W Catlin, EA AF Cadge, W Catlin, EA TI Making sense of suffering and death: How health care providers' construct meanings in a neonatal intensive care unit SO JOURNAL OF RELIGION & HEALTH LA English DT Article DE neonatology; health care providers; religion and spirituality; suffering; death ID SPIRITUALITY; BURNOUT; PHYSICIANS; MEDICINE; NURSES; STRESS; SATISFACTION; ORGANIZATION; BELIEFS; HOSPICE AB Biomedical technology has progressed at a pace that has created a new set of patient care dilemmas. Health care providers in intensive care units where life-sustaining therapies are both initiated and withdrawn encounter clinical scenarios that raise new existential, theological, and moral questions. We hypothesized that there might be broad patterns in how such staff understand these questions and make sense and meaning from their work. Such meaning making might be the key to working with the critically ill and dying while helping to create and sustain a meaningful context for personal living. This article presents themes evident in an in depth analysis of open-text responses to a spiritual and religious questionnaire survey completed by staff in one neonatal intensive care unit. The data reveal the central roles of perceived infant suffering and death in these providers' work experience and details how they understand the ultimate meaning of the suffering and death. We investigate patterns in how different providers articulate their individual attributes and motivations for working in intensive care. We found a surprising range of religious, spiritual, existential, and other meaning-making systems that underpin how staffs understand their work and how, certain of them, even define their purpose in life as caring for critically ill infants and their families. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Bowdoin Coll, Brunswick, ME 04011 USA. RP Catlin, EA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ecatlin@partners.org NR 52 TC 7 Z9 7 U1 1 U2 16 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0022-4197 J9 J RELIG HEALTH JI J. Relig. Health PD SUM PY 2006 VL 45 IS 2 BP 248 EP 263 DI 10.1007/s10943-006-9012-2 PG 16 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA 060EF UT WOS:000238784500009 ER PT J AU Pineles, SL Street, AE Koenen, KC AF Pineles, SL Street, AE Koenen, KC TI The differential relationships of shame-proneness and guilt-proneness to psychological and somatization symptoms SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMA-RELATED GUILT; SELF-CONCEALMENT; ATTRIBUTIONAL STYLE; HEALTH IMPLICATIONS; DISCLOSURE; PSYCHOPATHOLOGY; PSYCHOTHERAPY; INVENTORY; BEHAVIOR AB Historically, much attention has been focused on the role of guilt in psychopathology. However, recent theorists have posited that the association between guilt and psychopathology may be better accounted for by shame or by the overlapping features of guilt and shame. The current investigation assessed the relationships of shame-proneness versus guilt-proneness to psychological symptoms, somatization symptoms, attributional style, and concealment (n = 156). The shared variance between shame-proneness and guilt-proneness and the unique component of shame-proneness were related to both psychological and somatization symptoms, whereas the unique component of guilt-proneness was not related to these measures. Further, increased shame-proneness was associated with making depressogenic attributions, whereas guilt-proneness was not. Concealment was found to mediate the relationship between shame-proneness and psychological symptoms. These findings provide further evidence that the association between guilt and symptoms is accounted for by shame. Future research into concealment and other mechanisms by which shame influences symptoms is needed. C1 Boston Univ, Womens Hlth Sci Div, VA Boston Healthcare Syst, Sch Med,Natl Ctr PTSD, Boston, MA 02130 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Pineles, SL (reprint author), Boston Univ, Womens Hlth Sci Div, VA Boston Healthcare Syst, Sch Med,Natl Ctr PTSD, 116B-3, Boston, MA 02130 USA. EM Suzanne.Pineles@va.gov NR 46 TC 28 Z9 28 U1 4 U2 16 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 2006 VL 25 IS 6 BP 688 EP 704 DI 10.1521/jscp.2006.25.6.688 PG 17 WC Psychology, Clinical; Psychology, Social SC Psychology GA 057UD UT WOS:000238619800006 ER PT J AU Katz, A Niemierko, A Gage, I Evans, S Shaffer, M Fleury, T Smith, FP Petrucci, PE Flax, R Drogula, C Magnant, C AF Katz, A Niemierko, A Gage, I Evans, S Shaffer, M Fleury, T Smith, FP Petrucci, PE Flax, R Drogula, C Magnant, C TI Can axillary dissection be avoided in patients with sentinel lymph node metastasis? SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE sentinel lymph node; breast cancer; axillary dissection ID BREAST-CANCER PATIENTS; CARCINOMA-IN-SITU; RANDOMIZED-TRIAL; POSTOPERATIVE RADIOTHERAPY; PROGNOSTIC-SIGNIFICANCE; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; INVOLVEMENT; BIOPSY; LYMPHADENECTOMY AB Background: Who should undergo a completion dissection following identification of a +sentinel lymph node (SLN) is controversial. Methods: The records of 1, 133 patients who underwent SLN mapping were reviewed. The association between patient, tumor, and treatment characteristics and the presence of +SLNs and +nonSLNs was analyzed using two-way tables of frequency counts and Pearson chi(2) test. Possible predictors of +SLNs and +nonSLNs were analyzed using simple and multiple logistic regression. Results: One thousand one hundred forty-eight SLN procedures were performed. 367 procedures (32%) yielded +SLNs. For patients with a +SLN, on multiple logistic regression analysis LVSI, increasing numbers of +SLNs, decreasing numbers of negative SLNs, and increasing size of the largest SLN metastasis were statistically significantly associated with increased likelihood of nonSLN involvement. No subgroup was identified that did not have a significant rate of nonSLN involvement on completion axillary dissection, except those who had a large number of negative SLNs (>= 3) and small size of the largest SLN metastasis (<10 mm). Conclusions: A definitive answer to the question of who needs a completion axillary dissection awaits the results of ongoing trials. In the interim, our data does not support eliminating dissection for any subgroup of patients with +SLNs. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Sibley Mem Hosp, Washington, DC USA. RP Katz, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Cox 301, Boston, MA 02114 USA. EM abkatz@partners.org FU NCI NIH HHS [CA21239, CA50628] NR 46 TC 20 Z9 21 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUN 1 PY 2006 VL 93 IS 7 BP 550 EP 558 DI 10.1002/jso.20514 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 047QT UT WOS:000237894500008 PM 16705723 ER PT J AU Daly, PA AF Daly, PA TI Asperger's syndrome in young children: A developmental guide for parents and professionals. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Daly, PA (reprint author), Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2006 VL 45 IS 6 BP 761 EP 763 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 046CE UT WOS:000237788200022 ER PT J AU Daly, PA AF Daly, PA TI Asperger's syndrome: Intervening in schools, clinics and communities. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Daly, PA (reprint author), Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2006 VL 45 IS 6 BP 761 EP 763 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 046CE UT WOS:000237788200021 ER PT J AU Friedlander, AH Mahler, ME Yagiela, JA AF Friedlander, AH Mahler, ME Yagiela, JA TI Restless legs syndrome - Manifestations, treatment and dental im'plications SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE neurological movement disorders; dentistry; restless legs syndrome ID LIMB MOVEMENT-DISORDER; HEART-DISEASE; BACTERIAL-ENDOCARDITIS; DOPAMINE AGONISTS; SYNDROME RLS; EPIDEMIOLOGY; POPULATION; MANAGEMENT; DIAGNOSIS; SYMPTOMS AB Background. The authors reviewed the clinical features, epidemiology, pathogenesis and risk factors, medical management, dental findings and dental management of patients with restless legs syndrome (RLS). Types of Studies Reviewed. The authors conducted a MEDLINE search for the years 2000 through 2004 using the key terms "restless legs syndrome," "epidemiology," "pathophysiology," "treatment" and "dentistry." They selected articles published in English in peer-reviewed journals for further review, and they gave preference to articles reporting randomized controlled trials. Conclusions. RLS is a neurological disorder that is characterized by unpleasant sensations in the legs that occur at rest, especially at bedtime. These symptoms cause an irresistible urge to get out of bed and move the legs to relieve the discomfort, thereby delaying sleep onset and resulting in fatigue and dysphoria the next day. Clinical Implications. The prevalence of dental disease may be extensive in patients with RLS because of diminished salivary flow resulting from the medications used to treat RLS. Patient education, saliva substitutes and anticaries agents are indicated. Special precautions must be taken when prescribing or administering sedative-hypnotic agents that are likely to have adverse reactions with the medications used to treat RLS. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 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), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM friedlander@med.va.gov NR 43 TC 1 Z9 1 U1 0 U2 4 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 2006 VL 137 IS 6 BP 755 EP 761 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 053TZ UT WOS:000238329600016 PM 16803804 ER PT J AU Simmons, SF Schnelle, JF AF Simmons, SF Schnelle, JF TI Feeding assistance needs of long-stay nursing home residents and staff time to provide care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE staffing requirements; nursing homes; feeding assistance ID REFLECT DIFFERENCES; MEAL INTAKE; QUALITY; INCONTINENCE AB OBJECTIVES: To describe the staff time requirements to provide feeding assistance to nursing home residents who require three different types of assistance to improve oral food and fluid intake (social stimulation, verbal cuing, or both; physical guidance; or full physical assistance) and to determine whether physically dependent residents require more staff time, as defined in the national Resource Utilization Group System (RUGS) used for reimbursement. DESIGN: Descriptive. SETTING: Six skilled nursing homes. MEASUREMENTS: Ninety-one long-stay residents with low oral intake who responded to improved feeding assistance. PARTICIPANTS: Research staff conducted direct observations of usual nursing home care for 2 consecutive days (total of six meals) to measure oral food and fluid consumption (total percentage eaten) and staff time spent providing assistance (minutes and seconds). Research staff then implemented a standardized graduated-assistance protocol on 2 separate days (total of six meals) that enhanced residents' oral food and fluid intake. RESULTS: Staff time to provide feeding assistance that improved food and fluid consumption was comparable across different levels of eating dependency. Across all levels, residents required an average of 35 to 40 minutes of staff time per meal; thus, residents who needed only supervision and verbal cuing required just as much time as those who were physically dependent on staff for eating. CONCLUSION: The current RUGS system used for reimbursement likely underestimates the staff time required to provide feeding assistance care that improves oral intake. C1 Univ Calif Los Angeles, Borun Ctr Gerontol Res, Sch Med, Dept Geriatr,Jewish Home Aging, Reseda, CA 91335 USA. Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. RP Simmons, SF (reprint author), Univ Calif Los Angeles, Borun Ctr Gerontol Res, Sch Med, Dept Geriatr,Jewish Home Aging, 7150 Tampa Ave, Reseda, CA 91335 USA. EM ssimmons@ucla.edu FU NIA NIH HHS [AG 01026-01A1, AG 10415] NR 25 TC 48 Z9 52 U1 2 U2 2 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 2006 VL 54 IS 6 BP 919 EP 924 DI 10.1111/j.1532-5415.2006.00812.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 049EX UT WOS:000237999800006 PM 16776786 ER PT J AU Rudolph, JL Jones, RN Grande, LJ Milberg, WP King, EG Lipsitz, LA Levkoff, SE Marcantonio, ER AF Rudolph, JL Jones, RN Grande, LJ Milberg, WP King, EG Lipsitz, LA Levkoff, SE Marcantonio, ER TI Impaired executive function is associated with delirium after coronary artery bypass graft surgery SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc DE aged; delirium; CABG surgery; executive function; cognitive impairment; factor analysis ID CONFUSION ASSESSMENT METHOD; INTENSIVE-CARE UNIT; HOSPITALIZED-PATIENTS; RISK-FACTORS AB OBJECTIVES: To determine the extent to which preoperative performance on tests of executive function and memory was associated with delirium after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective observational cohort study. SETTING: Two academic medical centers and one Department of Veterans Affairs medical center in Massachusetts. PARTICIPANTS: Eighty subjects without preoperative delirium undergoing CABG or CABG-valve surgery completed baseline neuropsychological assessments with validated measures of memory and executive function. MEASUREMENTS: Beginning on postoperative Day 2, a battery to diagnose delirium was administered daily. Confirmatory factor analysis (CFA) was used to define two cognitive domain composites (memory and executive function). The loading pattern of neuropsychological measures onto the latent cognitive domains was determined a priori. Poisson regression was used to model the association between neuropsychological performance and cognitive domain composite scores and risk of postoperative delirium. The association was expressed as the difference between impaired (0.5 standard deviations (SDs) below mean) and nonimpaired (0.5 SDs above mean) performers. RESULTS: Forty subjects (50%) developed delirium. Measures of memory function were not significantly related to delirium. Of the executive function measures, verbal fluency, category fluency, Hopkins Verbal Learning Test learning, and backward recounting of days and months were significantly related to delirium. Preoperative mental status was a strong predictor of postoperative delirium. After controlling for age, sex, education, medical comorbidity, mental status, and the other cognitive domain, CFA cognitive domain composites suggest that risk for delirium is specific for executive functioning impairment (relative risk (RR) = 2.77, 95% confidence interval (CI) = 1.12-6.87) but not for memory impairment (RR = 0.49, 95% CI = 0.19-1.25). CONCLUSION: Worse preoperative performance in executive function was independently associated with greater risk of developing delirium after CABG. C1 GRECC, Boston VA Healthcare Syst, Dept Vet Affairs Boston Healthcare Syst, Boston, MA 02130 USA. Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. Brigham & Womens Hosp, Div Aging, Boston, MA USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA USA. RP Rudolph, JL (reprint author), GRECC, Boston VA Healthcare Syst, Dept Vet Affairs Boston Healthcare Syst, 150 S Huntington Ave,JP-122, Boston, MA 02130 USA. EM jrudolph@partners.org RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X FU NIA NIH HHS [K12 AG000294, 5K12 AG 00294-18, 5P60 AG 08812-14, P60 AG008812, P60 AG008812-10, P60 AG008812-11A10002, P60 AG008812-120002, T32 AG023480, T32 AG023480-01] NR 30 TC 60 Z9 67 U1 3 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 2006 VL 54 IS 6 BP 937 EP 941 DI 10.1111/j.1532-5415.2006.00735.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 049EX UT WOS:000237999800009 PM 16776789 ER PT J AU Carnes, M Schuler, L Sarto, GE Lent, SJ Bakken, L AF Carnes, M Schuler, L Sarto, GE Lent, SJ Bakken, L TI Increasing sex and ethnic/racial diversity of researchers in aging: Some promising strategies at the postdoctoral level SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ACADEMIC MEDICINE; GENDER; WOMEN; CAREER; FACULTY; GLASS; PRODUCTIVITY; PROMOTION; PROGRAM; TENURE AB To increase recruitment of a diverse pool of women into research careers in aging, a postdoctoral training program was designed based on the premise that women would be attracted to a research training program that focused on older women's health; offered an individualized, competency-based career development plan; could commit multiple years of financial support; and provided career mentorship by senior women faculty and that ethnic/racial minority women would be attracted to a research training program that, in addition to these other aspects, focused on the study of health differences and disparities between populations of older women. All 15 trainees have been women, and since focusing on health disparities, recruitment of underrepresented minority trainees increased from 10% to 80%. Of the nine former trainees, five continue research-based academic careers in aging with demonstrable success in achieving academic benchmarks. Focusing on areas of research with personal relevance to applicants and individualizing the program can be used to recruit diverse postdoctoral fellows in aging research. Short-term career outcomes indicate that career persistence of trainees compares favorably with that in other National Institutes of Health (NIH) postdoctoral training programs. C1 Univ Wisconsin, Ctr Womens Hlth Res, Madison, WI 53715 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. Univ Wisconsin, Dept Ind & Syst Engn, Madison, WI 53706 USA. Univ Wisconsin, Women Sci & Engn Leadership Inst, Madison, WI USA. Univ Wisconsin, Sch Vet Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Obstet & Gynecol, Madison, WI 53706 USA. Univ Wisconsin, Ctr Study Cultural Divers Healthcare, Madison, WI USA. Univ Wisconsin, Sch Educ, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Carnes, M (reprint author), Univ Wisconsin, Ctr Womens Hlth Res, 700 Regent St,Suite 301, Madison, WI 53715 USA. EM mlcarnes@wisc.edu FU NHLBI NIH HHS [K30 HL 04100-03]; NIA NIH HHS [T32 AG 00265, K07 AG000744, K07 AG 00744, K12 AG019247, K12 AG 19247, T32 AG000265] NR 41 TC 3 Z9 3 U1 1 U2 6 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 2006 VL 54 IS 6 BP 980 EP 985 DI 10.1111/j.1532-5415.2006.00739.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 049EX UT WOS:000237999800016 PM 16776796 ER PT J AU Harmon, W Meyers, K Ingelfinger, J McDonald, R McIntosh, M Ho, M Spaneas, L Palmer, JA Hawk, M Geehan, C Tinckam, K Hancock, WW Sayegh, MH AF Harmon, W Meyers, K Ingelfinger, J McDonald, R McIntosh, M Ho, M Spaneas, L Palmer, JA Hawk, M Geehan, C Tinckam, K Hancock, WW Sayegh, MH TI Safety and efficacy of a calcineurin inhibitor avoidance regimen in pediatric renal transplantation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID KIDNEY-TRANSPLANTATION; MYCOPHENOLATE-MOFETIL; ALLOGRAFT DYSFUNCTION; HLA ANTIBODIES; BASILIXIMAB INDUCTION; CLINICAL-SIGNIFICANCE; BORDERLINE CHANGES; SIROLIMUS RESCUE; RANDOMIZED TRIAL; GRAFT-SURVIVAL AB Thirty-four children were entered into a pilot trial of calcineurin inhibitor avoidance after living-donor kidney transplantation, the CN-01 study. Patients were treated with anti-CD25 mAb, prednisone, mycophenolate mofetil, and sirolimus. Twenty patients were maintained on the protocol for up to 3 yr of follow-up. One enrolled patient did not receive the transplant because of a donor problem, eight terminated because of one or more rejection episodes, four terminated because of adverse events, and one was lost to follow-up. Two grafts were lost, one as a result of chronic rejection and the other as a result of posttransplantation lymphoproliferative disorder. There were no deaths. The 6- and 12-mo acute rejection rates were 21.8 and 31.5%, respectively. GFR were stable throughout the course of the study, with a slight downward trend by 6 mo after transplantation followed by a slight upward trend to a mean of 70 ml/min thereafter. Early surveillance graft biopsies frequently showed focal interstitial mononuclear cellular infiltrates without overt vasculitis or tubulitis, but these infiltrates disappeared without treatment. Anti-HLA class I and II antibodies were detected in three patients before transplantation, and all three had acute rejections, including the two patients who lost their grafts. De novo anti-HLA Ab production occurred in only one patient after transplantation. There were two episodes of Epstein Barr virus-related posttransplantation lymphoproliferative disorder, one of which developed after the patient had been terminated from the study. It is concluded that calcineurin inhibitor-free immunosuppression can be safe and effective in pediatric living-donor renal transplantation. However, further modifications that are designed to lessen early rejection rates and decrease complications should be tested before this approach is used routinely. C1 Childrens Hosp Boston, Transplantat Res Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp Reg Med Ctr, Seattle, WA USA. EMMES Corp, Bethesda, MD USA. RP Harmon, W (reprint author), Childrens Hosp Boston, Transplantat Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM william.harmon@childrens.harvard.edu OI Tinckam, Kathryn/0000-0002-6638-2887 FU NCRR NIH HHS [RR00240, M01 RR02172]; NIAID NIH HHS [P01 AI50157, R01 AI54720, U01 AI46135] NR 64 TC 29 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2006 VL 17 IS 6 BP 1735 EP 1745 DI 10.1681/ASN.2006010049 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 047PL UT WOS:000237891100026 PM 16687625 ER PT J AU Li, Y Lin, XH AF Li, Y Lin, XH TI Semiparametric normal transformation models for spatially correlated survival data SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE asymptotic normality; consistency; Cox model; cross ratio; dependence measure; likelihood; population-average interpretation; semiparametric estimating equation; spatial dependence; spatial survival data ID COMPOSITE LIKELIHOOD APPROACH; FAILURE TIME DATA; ASYMPTOTIC THEORY; FRAILTY MODEL; DISTRIBUTIONS; STATISTICS; EQUATIONS; BOOTSTRAP; INFERENCE; VARIABLES AB There is an emerging interest in modeling spatially correlated survival data in biomedical and epidemiologic studies. In this article we propose a new class of semiparametric normal transformation models for right-censored spatially correlated survival data. This class of models assumes that survival outcomes marginally follow a Cox proportional hazard model with unspecified baseline hazard, and their joint distribution is obtained by transforming survival outcomes to normal random variables, whose joint distribution is assumed to be multivariate normal with a spatial correlation structure. A key feature of the class of semiparametric normal transformation models is that it provides a rich class of spatial survival models where regression coefficients have population average interpretation and the spatial dependence of survival times is conveniently modeled using the transformed variables by flexible normal random fields. We study the relationship of the spatial correlation structure of the transformed normal variables and the dependence measures of the original survival times. Direct nonparametric maximum likelihood estimation in such models is practically prohibited due to the high-dimensional intractable integration of the likelihood function and the infinite-dimensional nuisance baseline hazard parameter. We hence develop a class of spatial semiparametric estimating equations, which conveniently estimate the population-level regression coefficients and the dependence parameters simultaneously. We study the asymptotic properties of the proposed estimators and show that they are consistent and asymptotically normal. The proposed method is illustrated with an analysis of data from the East Boston Asthma Study, and its performance is evaluated using simulations. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Li, Y (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM yili@jinuny.harvard.edu; xlin@hsph.harvard.edu NR 46 TC 20 Z9 20 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 2006 VL 101 IS 474 BP 591 EP 603 DI 10.1198/016214505000001186 PG 13 WC Statistics & Probability SC Mathematics GA 049RD UT WOS:000238033200016 ER PT J AU Dubey, S Stephenson, P Levy, DE Miller, JA Keller, SM Schiller, JH Johnson, DH Kolesar, JM AF Dubey, Sarita Stephenson, Patricia Levy, Donna E. Miller, Judith A. Keller, Steven M. Schiller, Joan H. Johnson, David H. Kolesar, Jill M. CA Eastern Cooperative Oncology Grp TI EGFR dinucleotide repeat polymorphism as a prognostic indicator in non-small cell lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Intron 1; simple sequence repeat; allele ID GROWTH-FACTOR RECEPTOR; POSTOPERATIVE ADJUVANT THERAPY; BREAST-CANCER; INTRON-1 POLYMORPHISM; RANDOMIZED-TRIAL; GENE; MUTATIONS; TRANSCRIPTION; MODULATION; EXPRESSION AB Background: The epidermal growth factor receptor (EGFR) has been implicated in tumor growth and progression. Intron I of the EGFR gene contains a polymorphic simple sequence repeat (SSR) of 14 to 21 CA dinucleotides, the length of which correlates inversely with the level of EGFR transcription. The authors hypothesized that a shorter length of tumor SSR would be associated with poorer survival in patients with non-small cell lung cancer (NSCLC). Methods: Patients enrolled in Eastern Cooperative Oncology Group E3590 (a randomized, prospective trial of adjuvant therapy following resection of stages II and IIIa NSCLC) were randomized to radiation or radiation plus chemotherapy. Genomic DNA extracted from resected tumors was amplified for EGFR intron 1 by polymerase chain reaction and sequenced in a 3730XL DNA analyzer. Results: One hundred fifty-seven primary tumors were sequenced, 106 (68%) of which were heterozygous for intron 1. The most common genotypes were allele lengths of 17/19 dinucleotides (17.8%), 17/18 (11.4%), and 19/19 (11.4%). Allele status (homozygous versus heterozygous) did not correlate with race, gender, weight, performance status, histology, stage, or survival. Shorter allele length (<= 8 versus >18 CA dinucleotide repeats) was associated with squamous cell histology (p = 0.03). Allele sum of greater than 35 was associated with improved overall survival (log-rank p = 0.03, hazard ratio = 0.66). Conclusion: This is the first study to characterize the EGFR intron I SSR polymorphism in NSCLC. Tumors were most commonly heterozygous for SSR length. Squamous histology was associated with a shorter SSR. Longer sequences are associated with improved survival. C1 Univ Calif San Francisco, San Francisco, CA 94115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Vanderbilt Univ, Nashville, TN USA. RP Dubey, S (reprint author), Univ Calif San Francisco, 1600 Divisadero St,Box 1770, San Francisco, CA 94115 USA. EM sdubey@medicine.ucsf.edu RI Johnson, David/A-7437-2009 NR 25 TC 32 Z9 33 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2006 VL 1 IS 5 BP 406 EP 412 DI 10.1097/01243894-200606000-00005 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 066MH UT WOS:000239233300005 PM 17409891 ER PT J AU Wakelee, HA Wang, W Schiller, JH Langer, CJ Sandler, AB Belani, CP Johnson, DH AF Wakelee, Heather A. Wang, Wei Schiller, Joan H. Langer, Corey J. Sandler, Alan B. Belani, Chandra P. Johnson, David H. CA Eastern Cooperative Oncology Grp TI Survival differences by sex for patients with advanced non-small cell lung cancer on Eastern Cooperative Oncology Group trial 1594 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article; Proceedings Paper CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN SP Int Assoc Study Lung Canc DE non-small cell lung cancer; gender; survival ID DNA-DAMAGE; CHEMOTHERAPY; RESECTION; SMOKING; STAGE; SUSCEPTIBILITY; EXPRESSION; CISPLATIN; ESTROGEN; THERAPY AB Introduction: Previous data suggest that women may live longer with advanced non-small cell lung cancer (NSCLC) than men. We evaluated whether sex affected survival in the Eastern Cooperative Oncology Group (ECOG) E1594 trial. E1594 randomized patients with advanced NSCLC to one of four platinum doublets and found that all four regimens had comparable efficacy. Patients and Methods: Patients in the E 1594 database were divided into male and female cohorts; response and survival were calculated separately for each cohort. Known prognostic factors and differences in toxicity profiles were compared between the two cohorts. Results: All 1157 eligible patients (431 women, 726 men) from E1594 were included in this analysis. There was no statistically significant difference in performance status, weight loss of >10%, stage, or incidence of brain metastases between women and men. Response rates were similar (19% for both; P = 0.15). The median survival time for women, however, was significantly longer at 9.2 months (95% CI, 8.1-10.4 months) versus only 7.3 months for men (95% CI, 6.8-8.0 months) (P = 0.004 log-rank test). Toxicity was generally greater in women than in men. Conclusions: Women in ECOG 1594 had a 1.9-month statistically significant improvement in median survival compared with men, despite similar response rates and greater toxicity and no difference in other known prognostic factors. These data strongly support the significance of sex as a separate prognostic factor in advanced NSCLC and emphasize the importance of sex as a stratification factor in future phase III NSCLC trials. C1 Stanford Univ, Ctr Clin Canc, Dept Med, Div Oncol, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Univ Texas SW, Dept Med, Div Hematol Oncol, Dallas, TX USA. Fox Chase Canc Ctr, Dept Med, Div Oncol, Philadelphia, PA 19111 USA. Vanderbilt Univ, Dept Med, Div Oncol, Nashville, TN USA. Univ Pittsburgh, Dept Med, Div Oncol, Pittsburgh, PA USA. RP Wakelee, HA (reprint author), Stanford Univ, Ctr Clin Canc, Dept Med, Div Oncol, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM hwakelee@stanford.edu RI Johnson, David/A-7437-2009 NR 31 TC 59 Z9 60 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2006 VL 1 IS 5 BP 441 EP 446 DI 10.1097/01243894-200606000-00011 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 066MH UT WOS:000239233300011 PM 17409897 ER PT J AU Temel, JS Pirl, WF Recklitis, CJ Cashavelly, B Lynch, TJ AF Temel, Jennifer S. Pirl, William F. Recklitis, Christopher J. Cashavelly, Barbara Lynch, Thomas J. TI Feasibility and validity of a one-item fatigue screen in a thoracic oncology clinic SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE fatigue; lung cancer; screening ID CANCER-RELATED FATIGUE; QUALITY-OF-LIFE; HIGH-DOSE CHEMOTHERAPY; PHYSICAL PERFORMANCE; COMMUNITY ONCOLOGY; AEROBIC EXERCISE; EPOETIN ALPHA; PREVALENCE; PATIENT; OUTCOMES AB Introduction: Fatigue is one of the most common symptoms in patients with advanced cancers. Despite its high prevalence, it is often unrecognized and undetected. This study assessed the feasibility and validity of a one-item fatigue scale (OIFS) in an outpatient oncology clinic. Methods: Over a 3-month trial period, all patients in a thoracic oncology clinic were screened for fatigue with a one-item, 0 to 10 scale. Over a second trial period, an additional sample of 100 clinic patients completed validated measures of fatigue, including the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) and Fatigue Symptom Inventory (FSI), in addition to the OIFS. Results: During the initial trial period, more than 95% of patients (574 of 600) had a documented OIFS score on their first clinic visit. Data from the second cohort of patients revealed that the OIFS had good test-retest reliability (r = 0.88) and was highly correlated with the FSI severity scale (0.87) and the FACIT-F (-0.75). Receiver operating characteristic analysis showed the OIFS had good discrimination compared with the FACIT-F (area under the curve = 0.87). Sensitivity and specificity of several OIFS cutoff scores were compared, and scores between 3 and 5 were found to be optimal. Conclusions: The use of a one-item scale to screen for fatigue is feasible in an ambulatory clinic setting. This scale had convergent validity with other measures of fatigue and was able to identify cases of fatigue that met criteria on the FACIT-F. These data support the recommendations in the National Comprehensive Cancer Network guidelines for cancer-related fatigue screening. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Temel, JS (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey Bldg,7th Floor, Boston, MA 02114 USA. EM jtemel@partners.org NR 40 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD JUN PY 2006 VL 1 IS 5 BP 454 EP 459 DI 10.1097/01243894-200606000-00013 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 066MH UT WOS:000239233300013 PM 17409899 ER PT J AU Bhattacharyya, T Vrahas, MS Morrison, SM Kim, E Wiklund, RA Smith, RM Rubash, HE AF Bhattacharyya, T Vrahas, MS Morrison, SM Kim, E Wiklund, RA Smith, RM Rubash, HE TI The value of the dedicated orthopaedic trauma operating room SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE patient flow; operating room efficiency; orthopaedic trauma; trauma operating room; medical errors ID COST AB Background: Trauma centers and orthopaedic surgeons have traditionally been faced with limited operating room (OR) availability for fracture surgery. Orthopaedic trauma cases are often waitlisted and done late at night. We investigated the feasibility of having an unbooked orthopaedic trauma OR to reduce nighttime cases and improve OR flow. Methods: A retrospective analysis was performed for two 1 year time periods before and after the introduction of an unbooked trauma OR. The unbooked trauma OR is kept open for urgent and semi-urgent cases from 7:45 AM to 5 Pm 6 days per week, and is under the control of Orthopaedics; no elective cases are scheduled in the unbooked trauma room. We collected OR time data on two common surgical cases (dynamic hip screw and closed femoral nailing) done before and after introduction of the unbooked orthopaedic trauma OR. We also reviewed data on waitlist cases, surgical time, anesthetic times, OR utilization, and surgical complications before and after the introduction of the unbooked trauma room. Results: The availability of the unbooked trauma OR significantly improved operating suite flow. The proportion of hip fractures done after 5 Pm was reduced by 72% (p < 0.01). The number of all orthopaedic waitlist cases started after 5 Pm was reduced by 6% (p < 0.021). The distinct shift toward performing add-on cases during daytime hours resulted in a 6% reduction in OR over-utilization. Closed femoral nailing done at night required significantly more OR time (261 minutes versus 219 minutes, p < 0.04). Hip fracture surgeries and femoral nailings done at night were noted to have a higher incidence of surgical complications (p < 0.04 and p < 0.036). Conclusion: The availability of an unbooked orthopaedic trauma room resulted in a measurable shift from performing "add-on" cases to daytime surgery and may reduce complications. We recommend that hospitals and orthopaedic trauma services commit resources toward having an open OR reserved for orthopaedic trauma. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bhattacharyya, T (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey 3900,55 Fruit St, Boston, MA 02114 USA. EM tbhattacharyya@partners.org NR 12 TC 56 Z9 57 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JUN PY 2006 VL 60 IS 6 BP 1336 EP 1340 DI 10.1097/01.ta.0000220428.91423.78 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 053TR UT WOS:000238328700039 PM 16766980 ER PT J AU Kaysen, D Simpson, T Dillworth, T Larimer, ME Gutner, C Resick, PA AF Kaysen, D Simpson, T Dillworth, T Larimer, ME Gutner, C Resick, PA TI Alcohol problems and posttraumatic stress disorder in female crime victims SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID GENDER-DIFFERENCES; RISK-FACTORS; DEPENDENCE; WOMEN; TRAUMA; ABUSE; PTSD; INDIVIDUALS; RAPE AB Comorbidity between alcohol use and posttraumatic stress disorder (PTSD) has been well documented. However there are few longitudinal studies with acute trauma samples. The present study examined symptoms of alcohol use disorders (AUDs) and PTSD longitudinally after assault. Female sexual (n = 69) and physical assault victims (n = 39) were assessed 2 to 4 weeks and 3 months post trauma. Women who had lifetime AUD had higher intrusive and avoidance symptoms than those who did not have AUD. Women who had any alcohol problems had higher PTSD symptoms. Participants who had alcohol problems had the same pattern of symptom recovery as those who did not have alcohol problems but remained more symptomatic over the 3 months. These findings suggest hat early intervention strategies for women who have previous histories of alcohol problems and seek medical attention early post trauma may be indicated. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Missouri, St Louis, MO 63121 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. VA Boston Healthcare Syst, Boston, MA USA. RP Kaysen, D (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. EM dkaysen@.u.washington.edu FU NIAAA NIH HHS [F32 AA014728, F32-AA014728]; NIMH NIH HHS [R01 MH046992, R01 MH046992-05, R01-MH6992] NR 21 TC 23 Z9 23 U1 4 U2 5 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 2006 VL 19 IS 3 BP 399 EP 403 DI 10.1002/jts.20122 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 060AO UT WOS:000238773800009 PM 16788998 ER PT J AU Hinton, DE Chhean, D Pich, V Pollack, MH Orr, SP Pitman, RK AF Hinton, DE Chhean, D Pich, V Pollack, MH Orr, SP Pitman, RK TI Assessment of posttraumatic stress disorder in Cambodian refugees using the clinician-administered PTSD scale: Psychometric properties and symptom severity SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID PANIC-ATTACKS; PREVALENCE AB Posttraumatic stress disorder (PTSD) symptoms were assessed by using the Clinician-Administered PTSD Scale (CAPS) in a consecutive sample of Cambodian refugees attending a psychiatric clinic in the United States. Psychometric properties of the translated CAPS and severity of PTSD-related symptoms were examined. The CAPS demonstrated adequate psychometric properties, including coefficient alpha (92) and item-total correlations (48-85). Of the sample 56% (101/179) met Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for current PTSD. Those patients who met criteria for current PTSD had significantly higher CAPS total scores (M = 65.3, SD = 18.1) than those who did not meet the criteria (M = 13.9, SD = 16.7). C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Vet Affairs Med Ctr, Manchester, NH USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 22 TC 22 Z9 25 U1 0 U2 5 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 2006 VL 19 IS 3 BP 405 EP 409 DI 10.1002/jts.20115 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 060AO UT WOS:000238773800010 PM 16788999 ER PT J AU Garzotto, M AF Garzotto, M TI Expression and cellular localization of follicle-stimulating hormone receptor in normal human prostate, benign prostatic hyperplasia and prostate cancer - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Urol & Renal Transplantat, Portland, OR 97201 USA. RP Garzotto, M (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Urol & Renal Transplantat, Portland, OR 97201 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2006 VL 175 IS 6 BP 2077 EP 2077 DI 10.1016/S0022-5347(06)00659-8 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 043FJ UT WOS:000237585100028 ER PT J AU Kerfoot, BP Masser, BA DeWolf, WC AF Kerfoot, BP Masser, BA DeWolf, WC TI The continued decline of formal urological education of medical students in the United States: Does it matter? SO JOURNAL OF UROLOGY LA English DT Article DE education, medical; students, medical; urology; clinical clerkship ID DISEASES; AMERICA; SCHOOLS; CAREER AB Purpose: Survey analyses of 50 years document a substantial decline in the formal urological education of United States medical students, resulting in repeated calls by urologists to reverse this trend. Has this trend continued during the last decade? If so, should we be concerned? We performed a national survey to provide an updated assessment of urological education at United States medical schools. Materials and Methods: All 321 applicants to the 2003 to 2004 United States urology residency match and 527 applicants to a Boston area emergency medicine residency program in 2003 to 2004 from accredited United States medical schools were invited to participate in the study. On a validated, anonymous online survey, these students were asked 1) did their school offer a required and/or elective clinical rotation in urology, and 2) if so, what was its duration and in which year was it usually completed. Results: Curricular data were obtained on 110 of 125 (88%) accredited United States medical schools. Of United States schools 17% (17.3% SE 1.2%, 19 of 110) have required clinical rotations in urology; these required rotations are I to 2 weeks in duration and, in 79% of cases, conducted in year 3 of medical school. Those medical schools that require a clinical rotation in urology do not have a greater percentage of their students entering the urology match (Mann-Whitney U test p = 0.540). Conclusions: Formal urological education of United States medical students has continued to erode during the last decade, but the impact of this trend on student learning and career choice is not clear. Further research is required to determine whether these changes are of concern for the quality of applicants to urological training and for the future of urological care in the United States. C1 VA Boston Healthcare Syst, Dept Surg, Jamaica Plain, MA 02130 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. RP Kerfoot, BP (reprint author), VA Boston Healthcare Syst, Dept Surg, 150 Syst Huntington Ave,151DIA, Jamaica Plain, MA 02130 USA. EM drskerfoot@msn.com NR 17 TC 19 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2006 VL 175 IS 6 BP 2243 EP 2247 DI 10.1016/S0022-5347(06)00314-4 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 043FJ UT WOS:000237585100070 PM 16697847 ER PT J AU Tong, SC Eskey, CJ Pomerantz, SR Hirsch, JA AF Tong, SC Eskey, CJ Pomerantz, SR Hirsch, JA TI "SKyphoplasty": A single institution's initial experience SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID VERTEBRAL COMPRESSION FRACTURES; PERCUTANEOUS POLYMETHYLMETHACRYLATE VERTEBROPLASTY; KYPHOPLASTY; OSTEOPOROSIS; OUTCOMES; PAIN AB PURPOSE: The treatment of painful compression fractures has been revolutionized by vertebroplasty and kyphoplasty, two recently developed techniques that continue to evolve. This article describes a new device for the performance of kyphoplasty that uses a polymer device rather than a balloon to create a void in the bone. MATERIALS AND METHODS: In nine consecutive patients, kyphoplasty was performed at 12 vertebral levels with osteoporotic compression with use of the new SKy bone expander polymer device. RESULTS: The device was successful in creating a void in the bone at all levels. The procedure was also effective in alleviating pain from compression fractures. There were no technical failures or complications. CONCLUSION: The SKy bone expander polymer device is effective and safe for the performance of kyphoplasty to alleviate pain from vertebral compression fractures. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Lowell Gen Hosp, Commonwealth Radiol Associates, Lowell, MA USA. Dartmouth Hitchcock Med Ctr, Dept Radiol, Lebanon, NH 03766 USA. RP Hirsch, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM jahirsch@partners.org NR 12 TC 8 Z9 15 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUN PY 2006 VL 17 IS 6 BP 1025 EP 1030 DI 10.1097/01.RVI.0000222660.02990.27 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 053VR UT WOS:000238334500012 PM 16778237 ER PT J AU Campbell, J Rosenthal, DI Raskin, KA Hornicek, FJ Michaelson, MD AF Campbell, J Rosenthal, DI Raskin, KA Hornicek, FJ Michaelson, MD TI Use of an arterial tourniquet to achieve complete radiofrequency ablation of a renal metastasis SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID BLOOD-FLOW; VASCULAR OCCLUSION; THERMAL ABLATION; TISSUE ABLATION; LESION SIZE; LIVER; BONE; TUMORS; PATHOPHYSIOLOGY; CARCINOMA AB Radiofrequency (RF) coagulation of skeletal metastases is usually performed for pain relief. However, patients with solitary skeletal metastasis may benefit from more aggressive attempts to achieve local control. The authors report a case in which an arterial tourniquet was used to enhance the effectiveness of RF treatment of a calcaneal renal cell metastasis, leading to long-lasting local control with preservation of ambulation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Rosenthal, DI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM rosenthal.daniel@mgh.harvard.edu OI Michaelson, Dror/0000-0001-9249-6338 NR 26 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUN PY 2006 VL 17 IS 6 BP 1051 EP 1055 DI 10.1097/01.RVI.0000220368.94471.2C PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 053VR UT WOS:000238334500016 PM 16778241 ER PT J AU Raghunathan, A Rapp, JH Littooy, F Santilli, S Krupski, WC Ward, HB Thottapurathu, L Moritz, T McFalls, EO Investigators, C AF Raghunathan, A Rapp, JH Littooy, F Santilli, S Krupski, WC Ward, HB Thottapurathu, L Moritz, T McFalls, EO Investigators, C TI Postoperative outcomes for patients undergoing elective revascularization for critical limb ischemia and intermittent claudication: A subanalysis of the Coronary Artery Revascularization Prophylaxis (CARP) trial SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 16-19, 2005 CL Chicago, IL SP Soc Vasc Surg ID PERIOPERATIVE MYOCARDIAL-INFARCTION; VASCULAR-SURGERY; INFRAINGUINAL OPERATIONS; CARDIAC MORBIDITY; DISEASE; MANAGEMENT; MORTALITY; PERIOD AB Objective: To determine the perioperative mortality, myocardial infarction rate, and long-term survival of patients with critical limb ischemia (CLI) compared with those with intermittent claudication (IC) within a cohort selected for significant coronary artery disease, a secondary analysis was conducted of a prospective, randomized, multicenter trial of Coronary Artery Revascularization Prophylaxis (CARP) before peripheral vascular surgery. This multicenter trial was sponsored by the Cooperative Studies Program of the Department of Veterans Affairs. Methods. Of the 510 patients enrolled in the CARP trial and randomized to coronary revascularization or no revascularization before elective vascular surgery, 143 had CLI and 164 had IC as an indication for lower limb revascularization; > 95% of each group were men. The presence of coronary artery disease was determined by cardiac catheterization. Eligible patients had at least one treatable coronary lesion of >= 70%. Those with significant left main disease, ejection fraction of < 20%, and aortic stenosis were excluded. Patients were randomized to coronary artery disease revascularization or no revascularization before vascular surgery and followed for mortality and morbidity perioperatively and for a median of 2.7 years postoperatively. Medical treatment of coronary artery disease was pursued aggressively. Results. Patients with IC had a longer time from randomization to vascular surgery (p =.001) and more abdominal operations (p <.001). Patients with CLI had more urgent operations (p =.006), reoperations (p <.001), and limb loss (p =.008) as well as longer hospital stays (p <.001). The IC group had more perioperative myocardial infarctions (CLI, 8.4%; IC, 17.1%; p =.024), although perioperative mortality was similar (CLI, 3.5%; IC, 1.8%; p =.360). In follow-up, the IC group also had numerically more myocardial infarctions (CLI, 16.8%; IC, 25%; p =.079), but mortality was not different (CLI, 21%; IC, 22%; p =.825). Coronary artery revascularization did not lower perioperative or long-term mortality in either group. Conclusions. Our data indicate that patients with significant coronary artery disease and either CLI or IC can undergo vascular surgery with low mortality and morbidity, and these results are not improved by coronary artery revascularization before vascular surgery. Furthermore, when selected for the presence of symptomatically stable, severe coronary artery disease, there is no difference in long-term survival between patients with CLI and IC. Finally, the better-than-predicted outcomes for these patients with advanced systemic atherosclerosis may be due to aggressive medical management with beta-blockers, statins, and acetylsalicylic acid. C1 San Francisco VA Med Ctr, Vasc Serv Serv, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Edward Hines Jr VA Med Ctr, Chicago, IL USA. Univ Minnesota, Minneapolis, MN USA. Denver VA Med Ctr, Denver, CO USA. RP Rapp, JH (reprint author), San Francisco DVA Med Ctr, Surg Serv 112G, 4150 Clement St, San Francisco, CA 94121 USA. EM rappj@surgery.ucsf.edu NR 21 TC 26 Z9 30 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2006 VL 43 IS 6 BP 1175 EP 1181 DI 10.1016/j.jvs.2005.12.069 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 049VW UT WOS:000238046700019 PM 16765234 ER PT J AU Perron, MJ Stremlau, M Sodroski, J AF Perron, MJ Stremlau, M Sodroski, J TI Two surface-exposed elements of the B30.2/SPRY domain as potency determinants of N-tropic murine leukemia virus restriction by human TRIM5 alpha SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS RESTRICTION; B30.2(SPRY) DOMAIN; OLD-WORLD; HIV-1; INFECTION; VARIANTS; PRIMATES; CELLS; REF1; LV1 AB Human TRIM5 alpha (TRIM5 alpha(hu)) potently restricts N-tropic (N-MLV), but not B-tropic, murine leukemia virus in a manner dependent upon residue 110 of the viral capsid. Rhesus monkey TRIM5 alpha (TRIM5(rh)) inhibits N-MLV only weakly. The study of human-monkey TRIM5 alpha chimerae revealed that both the v1 and Q variable regions of the B30.2/SPRY domain contain potency determinants for N-MLV restriction. These variable regions are predicted to be surface-exposed elements on one face of the B30.2 domain. Acidic residues in v3 complement basic residue 110 of the N-MLV capsid. The results support recognition of the retroviral capsid by the TRIM5 alpha B30.2 domain. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIAID NIH HHS [AI 063987, AI 60354, P30 AI060354, R01 AI063987] NR 19 TC 45 Z9 46 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2006 VL 80 IS 11 BP 5631 EP 5636 DI 10.1128/JVI.00219-06 PG 6 WC Virology SC Virology GA 045PG UT WOS:000237753400054 PM 16699044 ER PT J AU Brezniceanu, ML Wei, CC Zhang, SL Hsieh, TJ Guo, DF Hebert, MJ Ingelfinger, JR Filep, JG Chan, JSD AF Brezniceanu, M-L Wei, C-C Zhang, S-L Hsieh, T-J Guo, D-F Hebert, M-J Ingelfinger, J. R. Filep, J. G. Chan, J. S. D. TI Transforming growth factor-beta 1 stimulates angiotensinogen gene expression in kidney proximal tubular cells SO KIDNEY INTERNATIONAL LA English DT Article DE TGF-beta 1; renin-anglotensin system; reactive oxygen species kidney ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; HIGH GLUCOSE; DIABETIC-NEPHROPATHY; INDUCED APOPTOSIS; EPITHELIAL-CELLS; MESANGIAL CELLS; EXTRACELLULAR-MATRIX; MYOCYTE APOPTOSIS; RAT HEPATOCYTES AB The present study investigated whether transforming growth factor-beta 1 (TGF-beta 1) exerts an autocrine positive effect on angiotensinogen (ANG) gene expression in rat kidney proximal tubular cells, and delineates its underlying mechanism(s) of action. Rat immortalized renal proximal tubular cells (IRPTCs) and freshly isolated mouse renal proximal tubules were incubated in the absence or presence of active human TGF-beta 1. IRPTCs were also stably transfected with rat TGF-beta 1 or p53 tumor suppressor protein (p53) cDNA in sense (S) and antisense (AS) orientations. ANG mRNA and p53 protein expression were assessed by reverse transcription-polymerase chain reaction and Western blotting, respectively. Reactive oxygen species (ROS) generation was quantified by lucigenin assay. Active TGF-beta 1 evoked ROS generation and stimulated ANG mRNA and p53 protein expression, whereas a superoxide scavenger and inhibitors of nicotinamide adenine dinucleotide oxidase and p38 mitogen-activated protein kinase (p38 MAPK) abolished the TGF-beta 1 effect. Stable transfer of p53 cDNA (S) enhanced and p53 cDNA (AS) abolished the stimulatory effect of TGF-beta 1 on ANG mRNA expression in IRPTCs. Our results demonstrate that TGF-beta 1 stimulates ANG gene expression and its action is mediated, at least in part, via ROS generation, p38 MAPK activation, and p53 expression, suggesting that angiotensin II and TGF-beta 1 may form a positive feedback loop to enhance their respective gene expression, leading to renal injury. C1 CHUM, Hotel Dieu, Ctr Rech, Montreal, PQ H2W 1T8, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. Univ Montreal, Hop Maison Neuve Rosemont, Ctr Rech, Montreal, PQ, Canada. RP Chan, JSD (reprint author), CHUM, Hotel Dieu, Ctr Rech, Pavillon Masson,3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM John.chan@umontreal.co FU NHLBI NIH HHS [HL-48455] NR 55 TC 38 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 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2006 VL 69 IS 11 BP 1977 EP 1985 DI 10.1038/sj.ki.5000396 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 050TS UT WOS:000238112100016 PM 16598193 ER PT J AU Fox, CS Larson, MG Hwang, SJ Leip, EP Rifai, N Levy, D Benjamin, EJ Murabito, JM Meigs, JB Vasan, RS AF Fox, C. S. Larson, M. G. Hwang, S-J Leip, E. P. Rifai, N. Levy, D. Benjamin, E. J. Murabito, J. M. Meigs, J. B. Vasan, R. S. TI Cross-sectional relations of serum aldosterone and urine sodium excretion to urinary albumin excretion in a community-based sample SO KIDNEY INTERNATIONAL LA English DT Article DE urinary albumin excretion; aldosterone; urine sodium; Framingham Heart Study; epidemiology ID PRONE HYPERTENSIVE-RATS; NITRIC-OXIDE; BLOOD-PRESSURE; GLOMERULAR HYPERFILTRATION; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; NONDIABETIC INDIVIDUALS; VASCULAR INJURY; RENAL-DISEASE AB Experimental models suggest that increased aldosterone and sodium intake are associated with renovascular damage and resultant proteinuria. We hypothesized that serum aldosterone and urinary sodium would be associated with urinary albumin excretion, an indicator of kidney damage. We evaluated 2700 participants (53% women, mean age 58 years) from the Framingham Offspring Study who attended a routine examination between 1995 and 1998, who were free of heart failure and renal failure, and underwent testing for serum aldosterone, spot urinary sodium, and urinary albumin excretion (urine albumin/ creatinine ratio, UACR), the latter two indexed to urinary creatinine. Stepwise multivariable linear regression was used to evaluate the relations between UACR with urinary sodium index and serum aldosterone. In multivariable regression, log urinary sodium index was associated positively with log-UACR (P < 0.0001). UACR levels in the fourth and fifth quintiles of urinary sodium index were 24% (95% confidence interval (Cl) 3-49%), and twofold higher (95% Cl 72-150%), respectively, relative to the lowest quintile (P-value for trend across quintiles < 0.001). In multivariable models, log-transformed aldosterone was not related to log-UACR. The top quintile of serum aldosterone levels was associated with a 21% higher (95% 1-44%) UACR levels relative to the lowest quintile. Urinary albumin excretion was strongly and positively associated in a continuous fashion with urinary sodium excretion, whereas a weaker nonlinear positive relation with serum aldosterone was noted. Our cross-sectional observations raise the possibility that dietary salt intake may be associated with early renovascular damage. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, LeDucq Ctr Cardiovasc Res, Dept Med,Med Sch, Boston, MA 02115 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Larson, Martin/0000-0002-9631-1254; Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01HL67288, 2K24HL04334, N01-HC-25195] NR 58 TC 33 Z9 34 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2006 VL 69 IS 11 BP 2064 EP 2069 DI 10.1038/sj.ki.5000378 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 050TS UT WOS:000238112100027 PM 16572107 ER PT J AU Sharma, PP Friesen, T Waites, KB AF Sharma, PP Friesen, T Waites, KB TI Influenza testing in the diagnostic laboratory SO LABMEDICINE LA English DT Article ID A H5N1; PATIENT AB Laboratory professionals need to understand the prevalence of influenza in the community, clinical manifestations and test characteristics for the proper use of rapid diagnostic tests. Rapid diagnosis of influenza is essential for reducing ancillary tests, decreasing inappropriate antibiotic use and guiding appropriate antiviral therapy. Differences in rapid influenza tests stem mainly from which type of virus is identified and whether it can differentiate between influenza A and B viral antigens. After reading this article, the reader should be able to understand the significance of viral influenza from an epidemiologic perspective, appreciate when tests to determine a microbiological diagnosis of influenza are indicated and select optimum methods for laboratory detection for use in physician offices and hospitals. Microbiology exam 70601 questions and corresponding answer form are located after the CE Update secon on p 375. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Sharma, PP (reprint author), Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD JUN PY 2006 VL 37 IS 6 BP 366 EP 370 DI 10.1309/TFED6CLTYW4A6VO6 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 047FU UT WOS:000237866000016 ER PT J AU Kang, HW Torres, D Wald, L Weissleder, R Bogdanov, AA AF Kang, HW Torres, D Wald, L Weissleder, R Bogdanov, AA TI Targeted imaging of human endothelial-specific marker in a model of adoptive cell transfer SO LABORATORY INVESTIGATION LA English DT Article DE E-selectin; endothelium; adoptive transfer; superparamagnetic iron oxide nanoparticles; MRI ID SOLUBLE E-SELECTIN; BREAST-CANCER; ADHESION MOLECULE-1; BLOOD-VESSELS; IN-VITRO; EXPRESSION; ANGIOGENESIS; ACTIVATION; DIFFERENTIATION; MICROVESSELS AB Imaging of endothelial-specific markers is critically important in non-invasive detection of early signs of vascular pathologies (eg inflammation, atherosclerosis and angiogenesis). A model of adoptive human endothelial cell ( HUVEC) transfer was used to test-specific imaging probes for human vascular disease consisting of cross-linked iron oxide (CLIO) nanoparticles conjugated to anti-human E-selectin (CLIO-F(ab')(2)). To perform in vivo imaging of E-selectin expression in functional blood vessels, human vascular endothelium cells (HUVECs) were implanted in athymic mice in Matrigel solution, which served as a temporary neovascularization scaffold after the solidification. The formation of HUVEC-containing vessels was established by histology and microscopy. CLIO-F(ab')(2) probes were administered via an i.v. injection following the induction of E-selectin expression by IL-1 beta. High-resolution MR images were obtained before and after the administration of CLIO-F(ab')(2), which showed specific hypointensity only if treated with IL-1 beta. A three-times higher CLIO-induced MR signal decrease on T2* images was measured in HUVEC implants in response to IL-1 beta treatment. Image signal intensity did not change in control animals that: (1) harbored Matrigel alone, (2) in the absence of IL-1 beta treatment or (3) in animals injected with CLIO linked to the idiotype-matched control F(ab')(2). Experiments in an adoptive transfer model demonstrated that HUVEC-containing neovessels are perfused and that IL-1 beta inducible E-selectin expression in these vessels is detectable with non-invasive imaging by using targeted nanoparticles. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, Dept Radiol & Cell Biol, S2-804,55 Lake Ave N, Worcester, MA 01655 USA. EM Alexei.Bogdanov@umassmed.edu RI Wald, Lawrence/D-4151-2009 FU NCI NIH HHS [5R01 CA74424-01, 1P50CA86355-01] NR 26 TC 48 Z9 48 U1 0 U2 6 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 2006 VL 86 IS 6 BP 599 EP 609 DI 10.1038/labinvest.3700421 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 044WH UT WOS:000237703500007 PM 16607378 ER PT J AU Lin, MY Timmer, FCA Oriel, BS Zhou, GW Guinan, JJ Kujawa, SG Herrmann, BS Merchant, SN Rauch, SD AF Lin, MY Timmer, FCA Oriel, BS Zhou, GW Guinan, JJ Kujawa, SG Herrmann, BS Merchant, SN Rauch, SD TI Vestibular evoked myogenic potentials (VEMP) can detect asymptomatic saccular hydrops SO LARYNGOSCOPE LA English DT Article DE Meniere disease; VEMP; vestibular evoked myogenic potentials; saccule; hydrops ID UNILATERAL MENIERES-DISEASE; ENDOLYMPHATIC HYDROPS; MULTIVARIATE-STATISTICS; TEMPORAL BONE; FOLLOW AB Objective: The objective of this study was to explore the useful of vestibular evoked myogenic potential (VEMP) testing for detecting endolymphatic hydrops, especially in the second ear of patients with unilateral Meniere disease (MD). Methods: This study was performed at a tertiary care academic medical center. Part I consisted of postmortem temporal bone specimens from the temporal bone collection of the Massachusetts Eye & Ear Infirmary; part II consisted of consecutive consenting adult patients (n = 82) with unilateral MD by American Academy of Otolaryngology-Head and Neck Surgery criteria case histories. Outcome measures consisted of VEMP thresholds in patients and histologic saccular endolymphatic hydrops in postmortem temporal bones. Results: Saccular hydrops was observed in the asymptomatic ear in six of 17 (35%) of temporal bones from donors with unilateral MD. Clinic patients with unilateral MD showed elevated mean VEMP thresholds and altered VEMP tuning in their symptomatic ears and, to a lesser degree, in their asymptomatic ears. Specific VEMP frequency and tuning criteria were used to define a "Meniere-like" response. This "Meniere-like" response was seen in 27% of asymptomatic ears of our patients with unilateral MD. Conclusions: Bilateral involvement is seen in approximately one third of MD cases. Saccular hydrops appears to precede symptoms in bilateral MD. Changes in VEMP threshold and tuning appear to be sensitive to these structural changes in the saccule. If so, then VEMP may be useful as a detector of asymptomatic saccular hydrops and as a predictor of evolving bilateral MD. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Kaohsiung Vet Gen Hosp, Haohsiung, Taiwan. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 charles St, Boston, MA 02114 USA. EM steven_rauch@meei.harvard.edu FU NIDCD NIH HHS [U24 DC008559, R01 DC004425, R01 DC04425, U24 DC008559-01] NR 15 TC 76 Z9 82 U1 0 U2 4 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 2006 VL 116 IS 6 BP 987 EP 992 DI 10.1097/01.mlg.0000216815.75512.03 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 049QJ UT WOS:000238031200027 PM 16735912 ER PT J AU Solban, N Rizvi, I Hasan, T AF Solban, Nicolas Rizvi, Imran Hasan, Tayyaba TI Targeted photodynamic therapy SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE photodynamic therapy; targeted delivery; photosensitizer ID GROWTH-FACTOR RECEPTOR; INTERNALIZING MONOCLONAL-ANTIBODIES; 5-AMINOLEVULINIC ACID; CANCER-CELLS; PROTOPORPHYRIN-IX; IN-VIVO; SUBCELLULAR-LOCALIZATION; OVARIAN-CANCER; CHLORIN E(6); LOW-DENSITY AB Background and Objectives: Photodynamic therapy (PDT) is an emerging modality for the treatment of various neoplastic and non-neoplastic pathologies. Study Design/Materials and Methods: PDT usually occurs when reactive oxygen species (ROS) generated from light-activated chemicals (photosensitizer, PS) destroy the target. For non-dermatologic applications the PS are delivered systemically and accumulate, at different concentrations, in most organs. Results and Conclusion: Typically there is a modest enhanced accumulation of the PS in tumor tissues, providing a first level of selectivity. Additional selectivity is provided by the confined illumination of the target area with the appropriate wavelength of light. For the treatment of pathologies in complex anatomical sites, such as in the peritoneal cavity, where restricted illumination is difficult; improved targeting of the PS is necessary to prevent damage to the surrounding healthy tissue. This article will focus on targeted PDT. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM thasan@partners.org OI Rizvi, Imran/0000-0001-9673-4700 FU NCI NIH HHS [P01 CA84203]; NIAMS NIH HHS [R01 AR40352] NR 65 TC 84 Z9 95 U1 2 U2 20 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD JUN PY 2006 VL 38 IS 5 BP 522 EP 531 DI 10.1002/lsm.20345 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 060SQ UT WOS:000238822300024 PM 16671102 ER PT J AU Navas, TA Nguyen, AN Hideshima, T Reddy, M Ma, JY Haghnazari, E Henson, M Stebbins, EG Kerr, I O'Young, G Kapoun, AM Chakravarty, S Mavunkel, B Perumattam, J Luedtke, G Dugar, S Medicherla, S Protter, AA Schreiner, GF Anderson, KC Higgins, LS AF Navas, TA Nguyen, AN Hideshima, T Reddy, M Ma, JY Haghnazari, E Henson, M Stebbins, EG Kerr, I O'Young, G Kapoun, AM Chakravarty, S Mavunkel, B Perumattam, J Luedtke, G Dugar, S Medicherla, S Protter, AA Schreiner, GF Anderson, KC Higgins, LS TI Inhibition of p38 alpha MAPK enhances proteasome inhibitor-induced apoptosis of myeloma cells by modulating Hsp27, Bcl-X-L, Mcl-1 and p53 levels in vitro and inhibits tumor growth in vivo SO LEUKEMIA LA English DT Article DE p38 alpha; myeloma; bortezomib; MG132; Hsp27; Mcl-1 ID ACTIVATED PROTEIN-KINASE; MULTIPLE-MYELOMA; PLASMA-CELLS; P38 MAPK; UP-REGULATION; SURVIVAL; INVOLVEMENT; PS-341; PUMA; EXPRESSION AB Inhibition of p38 kinase blocks the production of tumor-promoting factors in the multiple myeloma ( MM) bone marrow microenvironment. Proteasome inhibitors MG132 and bortezo-mib have been shown to have direct cytotoxic effects on MM cells. We show that a selective inhibitor of p38 alpha, SCIO-469, enhances the ability of MG132 and bortezomib to induce the apoptosis of MM cells. Previously, we showed that p38 inhibition with SCIO-469 enhances MM cytotoxicity of bortezomib by inhibiting the transient expression and phosphorylation of Hsp27, a downstream target of p38. Here we show that continued treatment of MM cells with bortezomib leads to a SCIO-469-enhanced downregulation of Hsp27 and to increased MM apoptosis. Furthermore, we show that p38 inhibition enhances the bortezomib-induced MM apoptosis by upregulation of p53 and downregulation of Bcl-X-L and McI-1. In a mouse xenograft plasmacytoma model of MM, we found that inhibiting p38 augments the effects of bortezomib in decreasing MM tumor growth in vivo. Thus, in addition to its role in suppressing an activated MM microenvironment, co-treatment with a p38 inhibitor, such as SCIO-469, may enhance the cytotoxicity of bortezomib by modulating pro-apoptotic and anti-apoptotic factors in MM cells, suggesting great potential for co-therapy. C1 Scios Nova Inc, Discovery Biol, Fremont, CA 94555 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Higgins, LS (reprint author), Scios Nova Inc, Discovery Biol, 6500 Paseo Padre Pkwy, Fremont, CA 94555 USA. EM lhiggin3@scius.jnj.com NR 35 TC 55 Z9 57 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 2006 VL 20 IS 6 BP 1017 EP 1027 DI 10.1038/sj.leu.2404200 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 046IZ UT WOS:000237806500015 PM 16617327 ER PT J AU Ganjoo, KN An, CS Robertson, MJ Gordon, LI Sen, JA Weisenbach, J Li, SL Weller, EA Orazi, A Horning, SJ AF Ganjoo, Kristen N. An, Caroline S. Robertson, Michael J. Gordon, Leo I. Sen, Joy A. Weisenbach, Jill Li, Shuli Weller, Edie A. Orazi, Attilio Horning, Sandra J. TI Rituximab, Bevacizumab and CHOP (RA-CHOP) in untreated diffuse large B-cell lymphoma: Safety, biomarker and pharmacokinetic analysis SO LEUKEMIA & LYMPHOMA LA English DT Article DE non-Hodgkin's lymphoma; diffuse large B-cell lymphoma; rituximab; bevacizumab; anti-angiogenesis; vascular endothelial growth factor; micro-vessel density ID ENDOTHELIAL GROWTH-FACTOR; NON-HODGKINS-LYMPHOMA; HUMANIZED MONOCLONAL-ANTIBODY; STANDARD REGIMEN CHOP; MICROVESSEL DENSITY; MULTIPLE-MYELOMA; PROGNOSTIC-SIGNIFICANCE; VASCULAR-PERMEABILITY; ADVANCED CANCER; SOLID TUMORS AB Bevacizumab is a humanized monoclonal antibody directed against vascular endothelial growth factor (VEGF-A). Non-Hodgkin's lymphomapatients with high serum VEGF levels have an inferior survival compared to patients with low VEGF levels. Bevacizumab was administered through a central line at 15 mg kg(-1) IV on day 1 followed by rituximab (R) and CHOP on day 2 for cycle 1 and day 1 for cycles 2-8. Serum levels of bevacizumab and R were measured at specified time points to assess pharmacokinetics (PK). Plasma and urine samples were also analysed for VEGF. Tumor samples were stained for VEGF, CD31 and factor VIII by immunohistochemistry. Thirteen patients with newly-diagnosed DLBCL received a total of 88 cycles (range 2-8, median 7). Best response included five CR, six PR, one SD and one PD with an overall response rate of 85% and complete response rate of 38%. The 12-month PFS is 77% and a median follow-up of 16.9 months for the surviving patients. All tumor samples stained strongly positive for VEGF and there was a marginal association between baseline plasma VEGF and response (p=0.04). Patients with higher plasma VEGF levels were generally younger and had bulky disease. Micro-vessel density did not correlate with presenting disease characteristics, VEGF expression or response. The PK of bevacizumab and rituximab were not influenced by combined treatment. In this patient population, treatment with RA-CHOP did not result in any episodes of grade 3 or 4 proteinuria, heart failure or hemorrhage. The RA-CHOP combination was generally well tolerated and safe. C1 Stanford Univ, Dept Med Oncol, Stanford, CA 94305 USA. Indiana Univ, Dept Hematol Oncol, Bloomington, IN 47405 USA. Northwestern Univ, Dept Med Oncol, Evanston, IL 60208 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Ganjoo, KN (reprint author), 3801 Miranda Ave 111 Onc, Palo Alto, CA 94304 USA. EM kganjoo@stanford.edu OI Gordon, Leo/0000-0003-1666-7064 NR 37 TC 73 Z9 77 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 2006 VL 47 IS 6 BP 998 EP 1005 DI 10.1080/10428190600563821 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 063RJ UT WOS:000239037000007 PM 16840188 ER PT J AU Stone, ME AF Stone, ME TI Don't leave me this way or when I get back on my feet you'll be sorry. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU REED BUSINESS INFORMATION PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JUN 1 PY 2006 VL 131 IS 10 BP 142 EP 142 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 051ED UT WOS:000238142800198 ER PT J AU Paige, NM Nouvong, A AF Paige, NM Nouvong, A TI The top 10 things foot and ankle specialists wish every primary care physician knew SO MAYO CLINIC PROCEEDINGS LA English DT Review ID PLANTAR FASCIITIS; ONYCHOMYCOSIS; MANAGEMENT AB Foot and ankle problems are common complaints of patients presenting to primary care physicians. These problems range from minor disorders, such as ankle sprains, plantar fasciitis, bunions, and Ingrown toenails, to more serious conditions such as Charcot arthropathy and Achilles tendon rupture. Early recognition and treatment of foot and ankle problems are imperative to avoid associated morbidities. Primary care physicians can address many of these complaints successfully but should be cognizant of which patients should be referred to a foot and ankle specialist to prevent common short-term and long-term complications. This article provides evidence-based pearls to assist primary care physicians in providing optimal care for their patients with foot and ankle complaints. C1 VA Greater Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90073 USA. RP Paige, NM (reprint author), VA Greater Los Angeles, David Geffen Sch Med, Dept Med, 11301 Wilshire Blvd 111A, Los Angeles, CA 90073 USA. EM neil.paige@med.va.gov NR 27 TC 5 Z9 5 U1 0 U2 2 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 2006 VL 81 IS 6 BP 818 EP 822 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 048SM UT WOS:000237966800014 PM 16770982 ER PT J AU Seshamani, M Zhu, JS Volpp, KG AF Seshamani, M Zhu, JS Volpp, KG TI Did postoperative mortality increase after the implementation of the medicare balanced budget act? SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Meeting of the Academy-of-Health-Services-Research-and-Health-Policy CY JUN 06-08, 2004 CL San Diego, CA SP Acad Hlth Serv Res & Hlth Policy DE health care delivery; health care reform; hospital quality; hospital reimbursement ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; HOSPITAL CHARACTERISTICS; PATIENT CHARACTERISTICS; ADMINISTRATIVE DATA; SURGICAL-PROCEDURES; OUTCOMES; COST; RATES AB Background: The Balanced Budget Act (BBA) of 1997 was a cost-saving measure designed to reduce Medicare reimbursements by $116.4 billion from 1998 to 2002. Resulting financial strain could adversely affect the quality of patient care in hospitals. Objective: We sought to determine whether 30-day mortality rates for surgical patients who developed complications changed at different rates in hospitals under different levels of financial strain from the BBA. Methods: Pennsylvania hospital discharge data, financial data, and death certificate data from 1997 to 2001 were obtained. A retrospective multivariate analysis examined whether 30-day mortality rates from 8 postoperative complications varied based on degree of hospital financial strain. Results: The average magnitude of Medicare payment reduction on overall hospital net revenues was estimated at 1.8% for hospitals with low BBA impact and 3.5% for hospitals with high impact in 1998, worsening to 2.0% and 4.8%, respectively, by 2001. Mortality rates changed at similar rates for high- and low-impact hospitals from 1997 to 1999, but from 1997 to 2000 mortality rates increased more among patients in high-impact compared with low-impact hospitals (P < 0.05). From 2000 to 2001, mortality rates among impact groups converged. There were no statistically significant differences based on BBA impact in changes in nursing-staff or length of stay. Conclusions: The mortality of surgical patients who developed postoperative complications increased to a greater degree in the short term in hospitals affected more by BBA. Measuring the quality impact of reimbursement cuts is necessary to understand cost-quality tradeoffs that may accompany cost-saving reforms. C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. RP Volpp, KG (reprint author), 1232 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu NR 41 TC 19 Z9 19 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2006 VL 44 IS 6 BP 527 EP 533 DI 10.1097/01.mlr.0000215886.49343.c6 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 050FN UT WOS:000238073000006 PM 16708001 ER PT J AU Sloan, KL Montez-Rath, ME Spiro, A Christiansen, CL Loveland, S Shokeen, P Herz, L Eisen, S Breckenridge, JN Rosen, AK AF Sloan, KL Montez-Rath, ME Spiro, A Christiansen, CL Loveland, S Shokeen, P Herz, L Eisen, S Breckenridge, JN Rosen, AK TI Development and validation of a psychiatric case-mix system SO MEDICAL CARE LA English DT Article DE risk adjustment; case-mix; behavioral health care; mental health; substance use disorders; psychiatry; disease burden; veterans ID OF-VETERANS-AFFAIRS; BEHAVIORAL HEALTH-CARE; RISK-ADJUSTMENT MODELS; MENTAL-HEALTH; AMBULATORY-CARE; 12-MONTH PREVALENCE; MOOD DISORDERS; AVERAGE COST; ERA VETERANS; VA AB Background: Although difficulties in applying risk-adjustment measures to mental health populations are increasingly evident, a model designed specifically for patients with psychiatric disorders has never been developed. Objective: Our objective was to develop and validate a case-mix classification system, the "PsyCMS," for predicting concurrent and future mental health (MH) and substance abuse (SA) healthcare costs and utilization. Subjects: Subjects included 914,225 veterans who used Veterans Administration (VA) healthcare services during fiscal year 1999 (FY99) with any MH/SA diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes 290.00-312.99, 316.00-316.99). Methods: We derived diagnostic categories from ICD-CM codes using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition definitions, clinical input, and empiric analyses. Weighted least-squares regression models were developed for concurrent (FY99) and prospective (FY00) MH/SA costs and utilization. We compared the predictive ability of the PsyCMS with several case-mix systems, including adjusted clinical groups, diagnostic groups, and the chronic illness and disability payment system. Model performance was evaluated using R-squares and mean absolute prediction errors (MAPEs). Results: Patients with MH/SA diagnoses comprised 29.6% of individuals seen in the VA during FY99. The PsyCMS accounted for distinct proportion of the variance in concurrent and prospective MH/SA costs (R-2 = 0.11 and 0.06, respectively), outpatient MH/SA utilization (R-2 = 0.25 and 0.07), and inpatient MH/SA utilization (R-2 = 0.13 and 0.05). The PsyCMS performed better than other case-mix systems examined with slightly higher R-squares and lower MAPEs. Conclusions: The PsyCMS has clinically meaningful categories, demonstrates good predictive ability for modeling concurrent and prospective MH/SA costs and utilization, and thus represents a useful method for predicting mental health costs and utilization. C1 VA Puget Sound Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Bedford VAMC 152, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Bedford VA Med Ctr, Bedford, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. VA Palo Alto Healthcare Syst, Palo Alto, CA USA. RP Sloan, KL (reprint author), VA Puget Sound Sound Hlth Care Syst, 111-ATC,1660 S Columbian Way, Seattle, WA 98108 USA. EM Kevin.Sloan@med.va.gov NR 44 TC 13 Z9 13 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2006 VL 44 IS 6 BP 568 EP 580 DI 10.1097/01.mlr.0000215819.76050.a1 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 050FN UT WOS:000238073000011 PM 16708006 ER PT J AU Jiang, SB AF Jiang, SB TI Technical aspects of image-guided respiration-gated radiation therapy SO MEDICAL DOSIMETRY LA English DT Article DE IMRT; IGRT ID REAL-TIME TUMOR; INSPIRATION BREATH-HOLD; DYNAMIC MULTILEAF COLLIMATOR; INTERNAL FIDUCIAL MARKERS; FRACTION ORGAN MOTION; IMRT DOSE DELIVERY; X-RAY SYSTEMS; DEEP-INSPIRATION; TRACKING RADIOTHERAPY; LUNG-TUMORS AB In this review article, we discuss various technical aspects of image-guided respiration-gated radiation therapy. We first review some basic concepts related to respiratory gating, including gating window, duty cycle, residual motion, internal/external gating, amplitude/phase gating, etc. We then discuss 2 implementations of image-guided respiration-gated treatment, i.e., the Mitsubishi/Hokkaido technique for internal gating and the NIGH technique for external gating. Several existing problems related to respiratory gating, namely external gating mode (phase vs. amplitude), imaging dose for internal gating, gated treatment for lung cancer without implanted fiducial makers, as well as gated intensity-modulated radiation therapy issues, are also discussed along with potential solutions. (c) 2006 American Association of Medical Dosimetrists. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jiang, SB (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM jiang.steve@mgh.harvard.edu NR 83 TC 74 Z9 77 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0958-3947 J9 MED DOSIM JI Med. Dosim. PD SUM PY 2006 VL 31 IS 2 BP 141 EP 151 DI 10.1016/j.meddos.2005.12.005 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 046NJ UT WOS:000237818000006 PM 16690455 ER PT J AU Trofimov, A Sharp, G Bortfeld, T AF Trofimov, A. Sharp, G. Bortfeld, T. TI Variability of waveforms and probability distributions in external respiratory-surrogate marker data SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 1986 EP 1986 DI 10.1118/1.2240136 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688500060 ER PT J AU Parodi, K Bortfeld, T Craft, D Mostagir, M Knopf, A AF Parodi, K. Bortfeld, T. Craft, D. Mostagir, M. Knopf, A. TI A novel filtering approach for local PET verification of proton radiotherapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Univ Heidelberg, Heidelberg, Germany. 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 2006 VL 33 IS 6 BP 1993 EP 1994 DI 10.1118/1.2240226 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688500089 ER PT J AU Wolfgang, J Mui, K Chu, A Sharp, G Chen, G AF Wolfgang, J. Mui, K. Chu, A. Sharp, G. Chen, G. TI Analysis of residual geometric artifacts from 4DCT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Boston Univ, Sch Med, Boston, MA 02118 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 2006 VL 33 IS 6 BP 2001 EP 2001 DI 10.1118/1.2240261 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688500122 ER PT J AU Liu, B AF Liu, B. TI Comparison of image quality in contact and magnification modes in digital mammography SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2014 EP 2014 DI 10.1118/1.2240754 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688500174 ER PT J AU Boldea, V Sharp, G Jiang, S Choi, N Ginestet, C Carrie, C Sarrut, D AF Boldea, V. Sharp, G. Jiang, S. Choi, N. Ginestet, C. Carrie, C. Sarrut, D. TI Implementation and evaluation of automatic contour propagation in 4DCT of lung SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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, Lyon, France. RI Sarrut, David/F-4849-2010; carrie, christian/K-5488-2014 OI Sarrut, David/0000-0002-4854-4141; carrie, christian/0000-0002-0766-2547 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 2006 VL 33 IS 6 BP 2019 EP 2020 DI 10.1118/1.2240779 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688500199 ER PT J AU Xu, Q Hamilton, R Jiang, S AF Xu, Q. Hamilton, R. Jiang, S. TI An optical flow based motion tracking method using fluoroscopic video SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Univ Arizona, Tucson, AZ USA. Massachusetts Gen Hosp, Boston, MA 02114 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 2006 VL 33 IS 6 BP 2025 EP 2025 DI 10.1118/1.2240803 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688500223 ER PT J AU Wu, Z Sharp, G Rietzel, E AF Wu, Z. Sharp, G. Rietzel, E. TI Evaluation of segmenting anatomical sub-regions for deformable registration of patient lung 4DCT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Gesell Schwerionenforsch mbH, D-6100 Darmstadt, Germany. 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 2006 VL 33 IS 6 BP 2034 EP 2034 DI 10.1118/1.2240837 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688500257 ER PT J AU Wolfsberger, L Tishler, R Allen, A James, S Killoran, J Court, L AF Wolfsberger, L. Tishler, R. Allen, A. James, S. Killoran, J. Court, L. TI Importance of daily portal imaging for head and neck IMRT treatments SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. NR 0 TC 3 Z9 3 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 2006 VL 33 IS 6 BP 2039 EP 2039 DI 10.1118/1.2240858 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688500278 ER PT J AU Sharp, G Jeung, A Tang, X Mostatavi, H Chen, G Jiang, S AF Sharp, G. Jeung, A. Tang, X. Mostatavi, H. Chen, G. Jiang, S. TI Respiratory gating with gantry mounted fluoroscopic imaging SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Varian Med Syst, Palo Alto, CA 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 2006 VL 33 IS 6 BP 2047 EP 2048 DI 10.1118/1.2240895 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501013 ER PT J AU Bert, C Rietzel, E Haberer, T Chen, G Kraft, G AF Bert, C. Rietzel, E. Haberer, T. Chen, G. Kraft, G. TI Treatment of moving targets with scanned ion beams: A comparison of different strategies SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Gesell Schwerionenforsch mbH, Darmstadt, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Heidelberg Ionenstrahl Therapie Ctr, Heidelberg, Germany. RI Bert, Christoph/C-2585-2013 OI Bert, Christoph/0000-0002-8539-6600 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 2006 VL 33 IS 6 BP 2049 EP 2049 DI 10.1118/1.2240902 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501020 ER PT J AU Gierga, DP Turcotte, JC Sharp, GC Ribold, M Franke, A Jiang, SB Chen, GTY AF Gierga, D. P. Turcotte, J. C. Sharp, G. C. Ribold, M. Franke, A. Jiang, S. B. Chen, G. T. Y. TI Uncertainties in target volume surrogates in image guided external beam partial breast irradiation SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Milan, Politecn, Milan, Italy. 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 2006 VL 33 IS 6 BP 2050 EP 2050 DI 10.1118/1.2240904 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501022 ER PT J AU Unkelbach, J Craft, D Halabi, T Bortfeld, T Oelfke, U AF Unkelbach, J. Craft, D. Halabi, T. Bortfeld, T. Oelfke, U. TI A mixed integer formulation for direct aperture optimization of IMRT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 German Canc Res Ctr, D-6900 Heidelberg, Germany. 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 2006 VL 33 IS 6 BP 2055 EP 2055 DI 10.1118/1.2240926 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501044 ER PT J AU Chan, TCY Bortfeld, T Tsitsiklis, JN AF Chan, T. C. Y. Bortfeld, T. Tsitsiklis, J. N. TI A robust approach to IMRT optimization SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 2006 VL 33 IS 6 BP 2061 EP 2061 DI 10.1118/1.2240982 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501070 ER PT J AU Hacker, F Rosca, F Friesen, S Zygmanski, P Ramakrishna, N AF Hacker, F. Rosca, F. Friesen, S. Zygmanski, P. Ramakrishna, N. TI Accuracy assessment of a non-invasive image guided system for intra-cranial linac based stereotactic radiosurgery SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 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 2006 VL 33 IS 6 BP 2066 EP 2066 DI 10.1118/1.2241001 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501089 ER PT J AU Court, L Tishler, R AF Court, L. Tishler, R. TI An experimental evaluation of the impact of setup uncertainty on dose near the surface for IMRT plans where the skin is considered a sensitive structure and is excluded from the PTV SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2069 EP 2069 DI 10.1118/1.2241013 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501101 ER PT J AU Wolfsberger, L Allen, A Tishler, R Court, L AF Wolfsberger, L. Allen, A. Tishler, R. Court, L. TI Conformal vs. IMRT concomitant boosts for IMRT based head and neck treatment SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2083 EP 2083 DI 10.1118/1.2241073 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501161 ER PT J AU Biggs, P AF Biggs, P. TI Determination of the effective chamber position of 2D ion chamber array using an HDR afterloading device SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2085 EP 2085 DI 10.1118/1.2241081 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501169 ER PT J AU Halabi, T Craft, D Bortfeld, T AF Halabi, T. Craft, D. Bortfeld, T. TI Dose-volume histogram objectives in multi-criteria IMRT optimization SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2089 EP 2089 DI 10.1118/1.2241101 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501189 ER PT J AU Mauceri, T Folkert, M Munro, J Chen AF Mauceri, T. Folkert, M. Munro, J. Chen TI Dosimetric characteristics of a titanium clad 90Y plaque for irradiation of sarcomas of the spine SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2090 EP 2090 DI 10.1118/1.2241103 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501191 ER PT J AU Seco, J Gierga, D Sharp, G Turcotte, J AF Seco, J. Gierga, D. Sharp, G. Turcotte, J. TI Effects of intra-fraction motion on IMRT treatment with segments of few monitor units SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2095 EP 2096 DI 10.1118/1.2241127 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501215 ER PT J AU Czerminska, M Zygmanski, P Court, L AF Czerminska, M. Zygmanski, P. Court, L. TI Evaluation of commercial QA software for independent IMRT dose calculations SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Dana Farber Brigham & Womens Canc Ctr, Boston, MA 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 2006 VL 33 IS 6 BP 2099 EP 2099 DI 10.1118/1.2241142 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501230 ER PT J AU Jaradat, AK Biggs, P AF Jaradat, A. K. Biggs, P. TI Measurement of neutron background in electron beams from a dedicated IORT linear accelerator and a conventional linear accelerator SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Univ Massachusetts, Lowell, MA 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 2006 VL 33 IS 6 BP 2120 EP 2120 DI 10.1118/1.2241241 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501320 ER PT J AU Zacharatou-Jarlskog, C Lee, C Jiang, H Bolch, W Xu, X Paganetti, H AF Zacharatou-Jarlskog, C. Lee, C. Jiang, H. Bolch, W. Xu, X. Paganetti, H. TI Monte Carlo simulations using whole-body pediatric and adult phantoms as virtual patients to assess secondary organ doses in proton radiation therapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Florida, Gainesville, FL USA. Rensselaer Polytech Inst, Troy, NY USA. NR 0 TC 4 Z9 4 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 2006 VL 33 IS 6 BP 2123 EP 2123 DI 10.1118/1.2241255 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501334 ER PT J AU Ahmad, M Song, H Lund, M Niemierko, A Moran, M Weidhaas, J Higgins, S Chen, Z Deng, J Nath, R AF Ahmad, M. Song, H. Lund, M. Niemierko, A. Moran, M. Weidhaas, J. Higgins, S. Chen, Z. Deng, J. Nath, R. TI Planning study of intensity-modulated and 3D conformal radiotherapy of whole pelvis including inguinal lymphatics: Radiobiological considerations for designing new fractionation schemes SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Yale New Haven Med Ctr, New Haven, CT 06504 USA. Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT 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 2006 VL 33 IS 6 BP 2129 EP 2129 DI 10.1118/1.2241281 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501359 ER PT J AU Court, L Tishler, R AF Court, L. Tishler, R. TI Planning strategies to reduce unnecessary skin dose in head and neck IMRT, including experimental verification SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2129 EP 2129 DI 10.1118/1.2241280 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501358 ER PT J AU Ionascu, D Jiang, SB Nishioka, S Lonberg, F Shirato, H Berbeco, RI AF Ionascu, D. Jiang, S. B. Nishioka, S. Lonberg, F. Shirato, H. Berbeco, R. I. TI Internal-external correlation investigations of respiratory, induced motion of lung tumors SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sapporo Med Coll, Sapporo, Hokkaido 060, Japan. Univ Massachusetts, Lowell, MA USA. Hokkaido Univ, Sapporo, Hokkaido, Japan. RI Shirato, Hiroki/A-7068-2010 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 2006 VL 33 IS 6 BP 2161 EP 2161 DI 10.1118/1.2241418 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501487 ER PT J AU Berbeco, RI Nishioka, S Shirato, H Jiang, SB AF Berbeco, R. I. Nishioka, S. Shirato, H. Jiang, S. B. TI Residual motion of lung tumors in end-of-inhale respiratory gating SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NTT Hosp, Sapporo, Hokkaido, Japan. 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 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 2006 VL 33 IS 6 BP 2162 EP 2163 DI 10.1118/1.2241423 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501492 ER PT J AU Cui, Y Dy, J Sharp, G Alexander, B Jiang, S AF Cui, Y. Dy, J. Sharp, G. Alexander, B. Jiang, S. TI Fluoroscopic tracking of lung tumor mass without implanted fiducial markers SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Northeastern Univ, Boston, MA 02115 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 2006 VL 33 IS 6 BP 2162 EP 2162 DI 10.1118/1.2241422 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501491 ER PT J AU Bortfeld, T Trofitnov, A Chan, T Martin, B Paganetti, H Jiang, S AF Bortfeld, T. Trofitnov, A. Chan, T. Martin, B. Paganetti, H. Jiang, S. TI Inverse planning optimization with organ motion probability SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2164 EP 2164 DI 10.1118/1.2241426 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688501495 ER PT J AU Jiang, S AF Jiang, S. TI 4D scanning SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 2006 VL 33 IS 6 BP 2181 EP 2181 DI 10.1118/1.2241491 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502046 ER PT J AU Lee, E Cha, K Bortfeld, T Deasy, J AF Lee, E. Cha, K. Bortfeld, T. Deasy, J. TI 4D-image-guided treatment planning optimization for management of organ motion in radiotherapy planning SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Georgia Inst Technol, Atlanta, GA 30332 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, St Louis, MO 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 2006 VL 33 IS 6 BP 2190 EP 2191 DI 10.1118/1.2241527 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502081 ER PT J AU Craft, D Bortfeld, T Halabi, T AF Craft, D. Bortfeld, T. Halabi, T. TI Multi-objective IMRT planning: A new algorithm, with clinical examples SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2192 EP 2192 DI 10.1118/1.2241531 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502085 ER PT J AU Bortfeld, T AF Bortfeld, T. TI Intro: Particles and intensity modulation SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2203 EP 2203 DI 10.1118/1.2241579 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502130 ER PT J AU Parodi, K Paganetti, H Shih, H Michaud, S Bortfeld, T AF Parodi, K. Paganetti, H. Shih, H. Michaud, S. Bortfeld, T. TI Dose-guided particle therapy with PET imaging SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 2 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 2006 VL 33 IS 6 BP 2203 EP 2204 DI 10.1118/1.2241582 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502133 ER PT J AU Suzuki, K Yoshida, H Nappi, J Armato, S Dachman, A AF Suzuki, K. Yoshida, H. Nappi, J. Armato, S. Dachman, A. TI Massive training artificial neural network (MTANN) to reduce false positives due to rectal tubes in computer-aided polyp detection SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Univ Chicago, Chicago, IL 60637 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 2006 VL 33 IS 6 BP 2208 EP 2208 DI 10.1118/1.2241602 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502152 ER PT J AU Chin, D Jahnke, L Cormack, R Tishler, R Court, L AF Chin, D. Jahnke, L. Cormack, R. Tishler, R. Court, L. TI Dynamic IMRT treatments of sinus region tumors: Comparison of Monte Carlo calculations with treatment planning system calculations and ion chamber measurements SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2220 EP 2220 DI 10.1118/1.2241649 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502197 ER PT J AU Kanoulas, E Aslam, J Sharp, G Berbeco, R Nishioka, S Shirato, H Jiang, S AF Kanoulas, E. Aslam, J. Sharp, G. Berbeco, R. Nishioka, S. Shirato, H. Jiang, S. TI Derivation of the tumor position from external respiratory surrogates with periodical updating of external/internal correlation SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Northeastern Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NTT Hosp, Dept Radiol, Sapporo, Hokkaido, Japan. Hokkaido Univ, Sch Med, Sapporo, Hokkaido 060, Japan. 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 2006 VL 33 IS 6 BP 2232 EP 2233 DI 10.1118/1.2241694 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502240 ER PT J AU Wu, H Sharp, G Shmukler, E Shirato, H Jiang, S AF Wu, H. Sharp, G. Shmukler, E. Shirato, H. Jiang, S. TI Statistical analysis of respiratory motion and knowledge discovery SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Indiana Univ Purdue Univ, Indianapolis, IN 46202 USA. Hokkaido Univ, Sapporo, Hokkaido, 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 2006 VL 33 IS 6 BP 2233 EP 2233 DI 10.1118/1.2241697 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502243 ER PT J AU Folkert, M Dedual, N Chen, G AF Folkert, M. Dedual, N. Chen, G. TI A biological lung phantom for IGRT studies SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northeastern Univ, 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 2006 VL 33 IS 6 BP 2234 EP 2234 DI 10.1118/1.2241699 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502245 ER PT J AU Folkert, M Mauceri, T Munro, J Chen, G AF Folkert, M. Mauceri, T. Munro, J. Chen, G. TI Influence of air gap on dosimetric characteristics of uniform and composite clinical 90Y plaques for dural irradiation SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2237 EP 2237 DI 10.1118/1.2241727 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502257 ER PT J AU Suit, H AF Suit, H. TI Radiation induced cancers in treated patients SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2238 EP 2238 DI 10.1118/1.2241734 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502262 ER PT J AU Xu, XG Paganetti, H AF Xu, X. G. Paganetti, H. TI Patient modeling and organ dose calculations using Monte Carlo methods SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Rensselaer Polytech Inst, Troy, NY 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 2006 VL 33 IS 6 BP 2239 EP 2239 DI 10.1118/1.2241737 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502265 ER PT J AU Cui, Y Dy, J Sharp, G Alexander, B Jiang, S AF Cui, Y. Dy, J. Sharp, G. Alexander, B. Jiang, S. TI Correlation score based respiratory gating for lung cancer radiotherapy without implanted fiducial markers SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Northeastern Univ, Boston, MA 02115 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 2006 VL 33 IS 6 BP 2244 EP 2244 DI 10.1118/1.2241759 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502285 ER PT J AU Tang, X Sharp, G Jiang, S AF Tang, X. Sharp, G. Jiang, S. TI Patient setup based on lung tumor mass for gated radiotherapy SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 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 2006 VL 33 IS 6 BP 2244 EP 2244 DI 10.1118/1.2241760 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502286 ER PT J AU Jiang, S AF Jiang, S. TI Radiographic & fluoroscopic guidance of respiratory sites SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 2006 VL 33 IS 6 BP 2245 EP 2245 DI 10.1118/1.2241765 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502290 ER PT J AU Chen, GTY Gierga, DP AF Chen, G. T. Y. Gierga, D. P. TI 3D surface imaging for PBI patient setup SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 2006 VL 33 IS 6 BP 2246 EP 2246 DI 10.1118/1.2241769 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502293 ER PT J AU Aljarrah, K Pope, C Jiang, SB AF Aljarrah, K. Pope, C. Jiang, S. B. TI Verification of the lung dose calculation of a commercial IMRT planning system using a realistic lung phantom SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Jordan Univ Sci & Technol, Irbid, Jordan. 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 2006 VL 33 IS 6 BP 2247 EP 2247 DI 10.1118/1.2241774 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502298 ER PT J AU Schofield, D Tishler, R Court, L AF Schofield, D. Tishler, R. Court, L. TI Differential smoothing IMRT planning for head and neck cancer patients with mediastinal involvement SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2257 EP 2257 DI 10.1118/1.2241815 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502337 ER PT J AU Paganetti, H Parodi, K Adams, J Kooy, H AF Paganetti, H. Parodi, K. Adams, J. Kooy, H. TI Clinical use of Monte Carlo in proton therapy: Pencil-beam algorithm vs Monte Carlo for proton therapy of skull-base and para-spinal tumors SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2286 EP 2286 DI 10.1118/1.2241929 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502446 ER PT J AU Schofield, D Court, L Allen, A Hacker, F Czerminska, M AF Schofield, D. Court, L. Allen, A. Hacker, F. Czerminska, M. TI Experimental evaluation of the accuracy of contralateral lung dose calculations for IMRT plans SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL 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 2006 VL 33 IS 6 BP 2286 EP 2287 DI 10.1118/1.2241930 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502447 ER PT J AU Chin, D Friedland, B Treister, N Cormack, R Tishler, R Court, L AF Chin, D. Friedland, B. Treister, N. Cormack, R. Tishler, R. Court, L. TI The effect of dental restorations and fixed prosthodontics on radiation therapy dose distribution: A Monte Carlo study SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 30-AUG 03, 2006 CL Orlando, FL SP Amer Assoc Physicists Med C1 Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 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 2006 VL 33 IS 6 BP 2294 EP 2294 DI 10.1118/1.2241961 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 058TW UT WOS:000238688502476 ER PT J AU Xiao, GP He, JX Rahme, LG AF Xiao, GP He, JX Rahme, LG TI Mutation analysis of the Pseudomonas aeruginosa mvfR and pqsABCDE gene promoters demonstrates complex quorum-sensing circuitry SO MICROBIOLOGY-SGM LA English DT Article ID TO-CELL COMMUNICATION; CAENORHABDITIS-ELEGANS; VIRULENCE FACTORS; SPECIFICITY; IDENTIFICATION; PATHOGENICITY; PATHOGENESIS; INFECTION; SYSTEMS; MODEL AB The LysR-type transcriptional regulator MvfR (PqsR) (multiple virulence factor regulator) plays a critical role in Pseudomonas aeruginosa pathogenicity via the transcriptional regulation of multiple quorum-sensing (QS)-regulated virulence factors. LasR activates full mvfR transcription, and MvfR subsequently activates pqsA-E expression. This study identifies and characterizes the key cis-regulatory elements through which mvfR and pqsA-E transcription is regulated in the highly virulent P. aeruginosa strain PA14. Deletion and site-directed mutagenesis indicate that: (1) LasR activates mvfR transcription by binding to a las/rhl box, CTAACAAAAGACATAG, centred at -513 by upstream of the MvfR translational start site; and (2) RhIR represses pqsA transcription by binding to a las/rhl box, CTGTGAGATTTGGGAG, centred at -311 by upstream of the pqsA transcriptional initiation site. Furthermore, it is shown that MvfR activates pqsA-E transcription by binding to a LysR box, TTCGGACTCCGAA, centred at -45 by relative to the pqsA transcriptional initiation site, demonstrating that this LysR box has a critical role in the physical interaction between the MvfR protein and the pqsA promoter. These results provide new insights into the regulatory relationships between LasR and mvfR, and between MvfR/RhIR and the pqs operon, and elucidate further the complex regulation of the P. aeruginosa QS circuitry. C1 Harvard Univ, Sch Med, Dept Surg Microbiol & Mol Genet, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02114 USA. Shriners Burns Inst, Boston, MA 02114 USA. RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Surg Microbiol & Mol Genet, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02114 USA. EM rahme@molbio.mgh.harvard.edu NR 29 TC 72 Z9 73 U1 1 U2 10 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 2006 VL 152 BP 1679 EP 1686 DI 10.1099/mic.0.28605-0 PN 6 PG 8 WC Microbiology SC Microbiology GA 056ZL UT WOS:000238563800011 PM 16735731 ER PT J AU Musch, G Venegas, JG AF Musch, G. Venegas, J. G. TI Positron emission tomography imaging of regional lung function SO MINERVA ANESTESIOLOGICA LA English DT Article; Proceedings Paper CT Symposium on Extension Anesthesia Resuscitation and Intensive Therapy CY MAY 10-12, 2006 CL Milan, ITALY DE positron, emission tomography; nitrogen isotopes; pulmonary gas exchange; respiratory distress syndrome, adult; asthma ID RESPIRATORY-DISTRESS-SYNDROME; PULMONARY BLOOD-FLOW; INHALED NITRIC-OXIDE; V/Q RATIOS; PET; VENTILATION; PERFUSION; INJURY; QUANTIFICATION; HUMANS AB Regional pulmonary perfusion and ventilation can be assessed by imaging, with positron emission tomography (PET), the pulmonary kinetics of [N-13]nitrogen (N-13(2)). Because of its low solubility in blood and tissues, N-13(2) infused intravenously in saline solution evolves into the alveolar airspace at first pass, where it accumulates in proportion to regional perfusion during a short apnea. In contrast, infused N-13(2) is not retained in non-aerated regions, which do not exchange gas. Robust estimates of regional perfusion and shunt are obtained by modeling the pulmonary kinetics of N-13(2) infused as a bolus during a short apnea. Regional ventilation is measured by modeling the washout of N-13(2) after breathing is resumed. Regional gas content and dead space ventilation can he measured with inhalation of N-13(2). Application of this novel functional imaging technique can further the understanding of the pathophysiology of a variety of pulmonary processes. This review briefly describes the methodological aspects of PET imaging of regional perfusion and ventilation and then focuses on insights in the pathophysiology of acute lung injury and asthma that have been gained by imaging the pulmonary kinetics of N-13(2) with PET. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Musch, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, CLN 309,55 Fruit St, Boston, MA 02114 USA. EM gmusch@partners.org FU NHLBI NIH HHS [HL-68011, HL-076464] NR 25 TC 10 Z9 10 U1 0 U2 1 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0375-9393 J9 MINERVA ANESTESIOL JI Minerva Anestesiol. PD JUN PY 2006 VL 72 IS 6 BP 363 EP 367 PG 5 WC Anesthesiology; Critical Care Medicine SC Anesthesiology; General & Internal Medicine GA 103WT UT WOS:000241918600004 PM 16682902 ER PT J AU Aikawa, E AF Aikawa, E. TI Cardiac valve remodelling - Implications for tissue engineering and molecular imaging SO MINERVA BIOTECNOLOGICA LA English DT Article DE cardiac valves, surgery; heart valves; heart ID BIOLOGICAL 3-DIMENSIONAL MATRIX; HEART-VALVES; ENDOTHELIAL-CELLS; INTERSTITIAL-CELLS; SMOOTH-MUSCLE; ADHESION MOLECULES; MITRAL-VALVE; IN-VITRO; TRANSCRIPTION FACTOR; PULMONARY AUTOGRAFT AB Approximately 275 000 patients annually receive a heart valve replacement worldwide. Although survival and quality of life are enhanced for many patients, prosthesis-associated complications and failure are frequent and have considerable impact on patient outcome. A fundamental problem of existing mechanical and biological prostheses is their failure to repair, remodel, and grow. Inability to grow with the patient is especially relevant to the pediatric population, which presently requires multiple reoperations; to place larger devices to accommodate their growth. Therefore, an off-the-shelf heart valve with the durability of mechanical prostheses, the biocompatibility of native valves, and the potential to grow is required. in this review, we focus primarily on the heart valve physiology and provide a summary of some of the aspects of valve regeneration, tissue engineering, and molecular imaging. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Aikawa, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St,Room 5420, Boston, MA 02129 USA. EM eaikawa@partners.org NR 69 TC 0 Z9 0 U1 0 U2 3 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 1120-4826 J9 MINERVA BIOTECNOL JI Minerva Biotechnol. PD JUN PY 2006 VL 18 IS 2 BP 65 EP 75 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 064BJ UT WOS:000239063900001 ER PT J AU Ishida-Takahashi, R Rosario, F Gong, YS Kopp, K Stancheva, Z Chen, XH Feener, EP Myers, MG AF Ishida-Takahashi, R Rosario, F Gong, YS Kopp, K Stancheva, Z Chen, XH Feener, EP Myers, MG TI Phosphorylation of Jak2 on Ser(523) inhibits Jak2-dependent leptin receptor signaling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-HORMONE RECEPTOR; TYROSINE KINASE TYK2; PROTEIN-KINASE; FEEDBACK INHIBITION; CATALYTIC ACTIVITY; ACTIVATION; DOMAIN; PATHWAYS; AUTOPHOSPHORYLATION; TRANSDUCTION AB The leptin receptor, LRb, and other cytokine receptors are devoid of intrinsic enzymatic activity and rely upon the activity of constitutively associated Jak family tyrosine kinases to mediate intracellular signaling. In order to clarify mechanisms by which Jak2, the cognate LRb-associated Jak kinase, is regulated and mediates downstream signaling, we employed tandem mass spectroscopic analysis to identify phosphorylation sites on Jak2. We identified Ser(523) as the first-described site of Jak2 serine phosphorylation and demonstrated that this site is phosphorylated on Jak2 from intact cells and mouse spleen. Ser(523) was highly phosphorylated in HEK293 cells independently of LRb-Jak2 activation, suggesting a potential role for the phosphorylation of Ser(523) in the regulation of LRb by other pathways. Indeed, mutation of Ser(523) sensitized and prolonged signaling by Jak2 following activation by the intracellular domain of LRb. The effect of Ser(523) on Jak2 function was independent of Tyr(570)-mediated inhibition. Thus, the phosphorylation of Jak2 on Ser(523) inhibits Jak2 activity and represents a novel mechanism for the regulation of Jak2-dependent cytokine signaling. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. RP Myers, MG (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM mgmyers@umich.edu FU NIDDK NIH HHS [P60 DK020572, R01 DK057768, P60 DK20572, R01 DK056731, DK36836, DK56731, P30 DK036836, R37 DK056731] NR 36 TC 38 Z9 39 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 2006 VL 26 IS 11 BP 4063 EP 4073 DI 10.1128/MCB.01589-05 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 046CU UT WOS:000237789800007 PM 16705160 ER PT J AU Deramaudt, TB Takaoka, M Upadhyay, R Bowser, MJ Porter, J Lee, A Rhoades, B Johnstone, CN Weissleder, R Hingorani, SR Mahmood, U Rustgi, AK AF Deramaudt, TB Takaoka, M Upadhyay, R Bowser, MJ Porter, J Lee, A Rhoades, B Johnstone, CN Weissleder, R Hingorani, SR Mahmood, U Rustgi, AK TI N-cadherin and keratinocyte growth factor receptor mediate the functional interplay between Ki-RAS(G12V) and p53(V143A) in promoting pancreatic cell migration, invasion, and tissue architecture disruption SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FGF-RECEPTOR; ESOPHAGEAL KERATINOCYTES; EPITHELIAL-CELLS; PLASMA-MEMBRANE; TRANSGENIC MICE; DUCTAL CELLS; P120 CATENIN; MOUSE MODEL; IN-VITRO; CANCER AB The genetic basis of pancreatic ductal adenocarcinoma, which constitutes the most common type of pancreatic malignancy, involves the sequential activation of oncogenes and inactivation of tumor suppressor genes. Among the pivotal genetic alterations are Ki-RAS oncogene activation and p53 tumor suppressor gene inactivation. We explain that the combination of these genetic events facilitates pancreatic carcinogenesis as revealed in novel three-dimensional cell (spheroid cyst) culture and in vivo subcutaneous and orthotopic xenotransplantation models. N-cadherin, a member of the classic cadherins important in the regulation of cell-cell adhesion, is induced in the presence of Ki-RAS mutation but subsequently downregulated with the acquisition of p53 mutation as revealed by gene microarrays and corroborated by reverse transcription-PCR and Western blotting. N-cadherin modulates the capacity of pancreatic ductal cells to migrate and invade, in part via complex formation with keratinocyte growth factor receptor and neural cell adhesion molecule and in part via interaction with p120-catenin. However, modulation of these complexes by Ki-RAS and p53 leads to enhanced cell migration and invasion. This preferentially induces the downstream effector AKT over mitogen-activated protein kinase to execute changes in cellular behavior. Thus, we are able to define molecules that in part are directly affected by Ki-RAS and p53 during pancreatic ductal carcinogenesis, and this provides a platform for potential new molecularly based therapeutic interventions. C1 Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Family Canc Res Inst, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Rustgi, AK (reprint author), Univ Penn, Div Gastroenterol, 415 Curie Blvd, Philadelphia, PA 19104 USA. EM anil2@mail.med.upenn.edu FU NCI NIH HHS [CA105008, R24 CA092782, U54 CA105008, R24-CA92782]; NIBIB NIH HHS [R01 EB001872, R01-EB001872]; NIDDK NIH HHS [P30 DK050306, P30 DK50306] NR 60 TC 26 Z9 27 U1 0 U2 3 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 2006 VL 26 IS 11 BP 4185 EP 4200 DI 10.1128/MCB.01055-05 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 046CU UT WOS:000237789800017 PM 16705170 ER PT J AU Gwack, Y Sharma, S Nardone, J Tanasa, B Iuga, A Srikanth, S Okamura, H Bolton, D Feske, S Hogan, PG Rao, AJ AF Gwack, Y Sharma, S Nardone, J Tanasa, B Iuga, A Srikanth, S Okamura, H Bolton, D Feske, S Hogan, PG Rao, AJ TI A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT SO NATURE LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; TO-EMBRYO TRANSITION; PROTEIN-KINASES; DUAL-SPECIFICITY; ACTIVATION-LOOP; CA2+ SENSOR; CALCIUM; CELLS; STORE; GSK-3 AB Precise regulation of the NFAT ( nuclear factor of activated T cells) family of transcription factors (NFAT1 - 4) is essential for vertebrate development and function(1). In resting cells, NFAT proteins are heavily phosphorylated and reside in the cytoplasm; in cells exposed to stimuli that raise intracellular free Ca2+ levels, they are dephosphorylated by the calmodulin-dependent phosphatase calcineurin and translocate to the nucleus(1). NFAT dephosphorylation by calcineurin is countered by distinct NFAT kinases, among them casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3)(1-5). Here we have used a genome-wide RNA interference ( RNAi) screen in Drosophila(6,7) to identify additional regulators of the signalling pathway leading from Ca2+- calcineurin to NFAT. This screen was successful because the pathways regulating NFAT subcellular localization (Ca2+ influx, Ca2+ - calmodulin calcineurin signalling and NFAT kinases) are conserved across species(8,9), even though Ca2+-regulated NFAT proteins are not themselves represented in invertebrates. Using the screen, we have identified DYRKs (dual-specificity tyrosine-phosphorylation regulated kinases) as novel regulators of NFAT. DYRK1A and DYRK2 counter calcineurin-mediated dephosphorylation of NFAT1 by directly phosphorylating the conserved serine-proline repeat 3 (SP-3) motif of the NFAT regulatory domain, thus priming further phosphorylation of the SP-2 and serine-rich region 1 (SRR1) motifs by GSK3 and CK1, respectively. Thus, genetic screening in Drosophila can be successfully applied to cross evolutionary boundaries and identify new regulators of a transcription factor that is expressed only in vertebrates. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rao, AJ (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu OI Feske, Stefan/0000-0001-5431-8178 NR 30 TC 228 Z9 241 U1 3 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 1 PY 2006 VL 441 IS 7093 BP 646 EP 650 DI 10.1038/nature04631 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048AU UT WOS:000237920800050 PM 16511445 ER PT J AU Love, JC Ronan, JL Grotenbreg, GM van der Veen, AG Ploegh, HL AF Love, JC Ronan, JL Grotenbreg, GM van der Veen, AG Ploegh, HL TI A microengraving method for rapid selection of single cells producing antigen-specific antibodies SO NATURE BIOTECHNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; ESCHERICHIA-COLI; ARRAYS; COMPATIBILITY; HYBRIDOMAS; MICROWELLS; CLONING AB Monoclonal antibodies that recognize specific antigens of interest are used as therapeutic agents and as tools for biomedical research(1). Discovering a single monoclonal antibody requires retrieval of an individual hybridoma from polyclonal mixtures of cells producing antibodies with a variety of specificities. The time required to isolate hybridomas by a limiting serial-dilution, however, has restricted the diversity and breadth of available antibodies. Here we present a soft lithographic method based on intaglio printing to generate microarrays comprising the secreted products of single cells. These engraved arrays enable a rapid (< 12 h) and high-throughput (> 100,000 individual cells) system for identification, recovery and clonal expansion of cells producing antigen-specific antibodies. This method can be adapted, in principle, to detect any secreted product in a multiplexed manner. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. RP Love, JC (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM love@cbrinstitute.org; ploegh@wi.mit.edu NR 25 TC 185 Z9 192 U1 8 U2 52 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 2006 VL 24 IS 6 BP 703 EP 707 DI 10.1038/nbt1210 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 051UQ UT WOS:000238187300033 PM 16699501 ER PT J AU Carroll, DK Carroll, JS Leong, CO Cheng, F Brown, M Mills, AA Brugge, JS Ellisen, LW AF Carroll, DK Carroll, JS Leong, CO Cheng, F Brown, M Mills, AA Brugge, JS Ellisen, LW TI p63 regulates an adhesion programme and cell survival in epithelial cells SO NATURE CELL BIOLOGY LA English DT Article ID STEM-CELLS; P53 HOMOLOG; EPIDERMAL MORPHOGENESIS; EXPRESSION; APOPTOSIS; DELTA-NP63-ALPHA; INTEGRIN; MATRIX; NICHE; SKIN AB p63 is critical for epithelial development yet little is known about the transcriptional programmes it regulates. By characterising transcriptional changes and cellular effects following modulation of p63 expression, we have defined a vital role for p63 in cellular adhesion. Knockdown of p63 expression caused downregulation of cell adhesion-associated genes, cell detachment and anoikis in mammary epithelial cells and keratinocytes. Conversely, overexpression of the TAp63 gamma or Delta Np63 alpha isoforms of p63 upregulated cell adhesion molecules, increased cellular adhesion and conferred resistance to anoikis. Apoptosis induced by loss of p63 was rescued by signalling downstream of beta 4 integrin. Our results implicate p63 as a key regulator of cellular adhesion and survival in basal cells of the mammary gland and other stratified epithelial tissues. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NYU, Courant Inst Math Sci, Bioinformat Grp, New York, NY 10003 USA. NYU, Dept Biol, New York, NY 10003 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM joan_brugge@hms.harvard.edu OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA080111]; NIAMS NIH HHS [AR47898]; NIDCR NIH HHS [DE15945-01, R01 DE015945] NR 42 TC 249 Z9 252 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUN PY 2006 VL 8 IS 6 BP 551 EP 561 DI 10.1038/ncb1420 PG 11 WC Cell Biology SC Cell Biology GA 049PR UT WOS:000238029000007 PM 16715076 ER PT J AU Seminara, SB AF Seminara, SB TI Mechanisms of Disease: the first kiss - a crucial role for kisspeptin-1 and its receptor, G-protein-coupled receptor 54, in puberty and reproduction SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Review DE G-protein-coupled receptor 54; genetics; idiopathic hypogonadotropic hypogonadism; kisspeptin; metastin ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; PROTEIN-COUPLED RECEPTOR; PITUITARY-GONADAL AXIS; PROSTATE-CANCER; HYPOTHALAMIC AMENORRHEA; MESSENGER-RNA; OPEN-LABEL; GPR54; PEPTIDE AB Although the hypothalamic secretion of gonadotropin-releasing hormone (GnRH) is the defining hormonal event of puberty, the physiologic mechanisms that drive secretion of GnRH at the time of sexual maturation have been difficult to identify. After puberty is initiated, the factors that modulate the frequency and amplitude of GnRH secretion in rapidly changing sex-steroid environments (i.e. the female menstrual cycle) also remain unknown. The discovery that, in both humans and mouse models, loss-of-function mutations in the gene that encodes G-protein-coupled receptor 54 result in phenotypes of hypogonadotropic hypogonadism with an absence of pubertal development has unearthed a novel pathway regulating GnRH secretion. Ligands for G-protein-coupled receptor 54 (KiSS-1R), including metastin (derived from the parent compound, kisspeptin-1) and metastin's C-terminal peptide fragments, have been shown to be powerful stimulants for GnRH release in vivo via their stimulation of G-protein-coupled receptor 54. This article reviews the discovery of the GPR54 gene, places it into the appropriate biological context, and explores the data from in vitro and in vivo studies that point to this ligand-receptor system as a major driver of GnRH secretion. C1 Harvard Univ, Sch Med, Boston, MA USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 505,Fruit St, Boston, MA 02114 USA. EM sseminara@partners.org FU NICHD NIH HHS [U54 HD028138, R01 HD043341] NR 48 TC 26 Z9 28 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD JUN PY 2006 VL 2 IS 6 BP 328 EP 334 DI 10.1038/ncpendmet0139 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 048RX UT WOS:000237965300010 PM 16932310 ER PT J AU Sadri-Vakili, G Cha, JHJ AF Sadri-Vakili, G Cha, JHJ TI Mechanisms of disease: histone modifications in Huntington's disease SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Review DE chromatin; histone deacetylase inhibitors; histories; Huntington's disease; transcription ID SUBEROYLANILIDE HYDROXAMIC ACID; ORAL SODIUM PHENYLBUTYRATE; GENE-EXPRESSION CHANGES; DEACETYLASE INHIBITORS; MOUSE MODEL; MUTANT HUNTINGTIN; TRANSGENIC MICE; TRANSCRIPTIONAL DYSREGULATION; EXPANDED POLYGLUTAMINE; TRINUCLEOTIDE REPEATS AB Huntington's disease (HD) is an autosomal neurodegenerative disorder caused by a polyglutamine repeat expansion within the huntingtin protein. HD is characterized by problems with movement, cognition and behavioral functioning, and there is currently no effective treatment. Although multiple patholgic mechanisms have been proposed, the exact mechanism by which mutant huntingtin causes neural dysfunction is not known. Recent studies demonstrating altered messenger RNA expression point to transcriptional dysregulation as a central mechanism. The control os eukaryotic gene expression depends on modification of histone proteins associated with specific genes, with histone acetylation playing a crucial role. Studies in numerous HD models have shown that mutant huntingtin alters acetyltransferase activity, and indicate aberrant activity of this enzyme might be an underlying mechanism of transcriptional dysregulation is HD. Furthermore, recent studies have shown a therapeutic role for histone deacetylase inhibitors in a number of HD models. In this review, we summarize the current state of knowledge regarding the status of histones in HD. In addition, we discuss how these histone modifications not only lead to pathogenesis, but might also provide a novel therapeutic strategy for treating this devastating disease. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St,CNY 114-2001, Charlestown, MA 02129 USA. EM cha@helix.mgh.harvard.edu FU NINDS NIH HHS [NS045242, NS038106] NR 73 TC 64 Z9 65 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD JUN PY 2006 VL 2 IS 6 BP 330 EP 338 DI 10.1038/ncpneuro0199 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 043TI UT WOS:000237624100012 PM 16932577 ER PT J AU Arking, DE Pfeufer, A Post, W Kao, WHL Newton-Cheh, C Ikeda, M West, K Kashuk, C Akyol, M Perz, S Jalilzadeh, S Illig, T Gieger, C Guo, CY Larson, MG Wichmann, HE Marban, E O'Donnell, CJ Hirschhorn, JN Kaab, S Spooner, PM Meitinger, T Chakravarti, A AF Arking, DE Pfeufer, A Post, W Kao, WHL Newton-Cheh, C Ikeda, M West, K Kashuk, C Akyol, M Perz, S Jalilzadeh, S Illig, T Gieger, C Guo, CY Larson, MG Wichmann, HE Marban, E O'Donnell, CJ Hirschhorn, JN Kaab, S Spooner, PM Meitinger, T Chakravarti, A TI A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization SO NATURE GENETICS LA English DT Article ID NITRIC-OXIDE SYNTHASE; CORONARY-HEART-DISEASE; FACTOR-H POLYMORPHISM; ALL-CAUSE MORTALITY; QT-INTERVAL; MACULAR DEGENERATION; CARDIOVASCULAR MORTALITY; QUANTITATIVE TRAIT; ELDERLY-MEN; K+ CHANNEL AB Extremes of the electrocardiographic QT interval, a measure of cardiac repolarization, are associated with increased cardiovascular mortality. We identified a common genetic variant influencing this quantitative trait through a genome-wide association study on 200 subjects at the extremes of a population-based QT interval distribution of 3,966 subjects from the KORA cohort in Germany, with follow-up screening of selected markers in the remainder of the cohort. We validated statistically significant findings in two independent samples of 2,646 subjects from Germany and 1,805 subjects from the US Framingham Heart Study. This genome-wide study identified NOS1AP ( CAPON), a regulator of neuronal nitric oxide synthase, as a new target that modulates cardiac repolarization. Approximately 60% of subjects of European ancestry carry at least one minor allele of the NOS1AP genetic variant, which explains up to 1.5% of QT interval variation. C1 Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Tech Univ Munich, Inst Human Genet, D-81675 Munich, Germany. GSF, Natl Res Ctr Environm & Hlth, Inst Human Genet, D-85764 Neuherberg, Germany. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. GSF, Natl Res Ctr Environm & Hlth, Inst Epidemiol, D-85764 Neuherberg, Germany. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Univ Munich, Inst Informat Management Biometry & Epidemiol, D-81377 Munich, Germany. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Program Genom, Boston, MA 02115 USA. Univ Munich, Dept Med 1, D-81377 Munich, Germany. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Chakravarti, A (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. EM aravinda@jhmi.edu RI Kaab, Stefan/H-3915-2012; Pfeufer, Arne/B-6634-2013; Meitinger, Thomas/O-1318-2015; AKYOL, Mahmut/C-2490-2016; OI Gieger, Christian/0000-0001-6986-9554; Larson, Martin/0000-0002-9631-1254 FU NHLBI NIH HHS [N01-HC-25195, 5U01HL066582, K23HL080025] NR 45 TC 330 Z9 340 U1 0 U2 10 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 2006 VL 38 IS 6 BP 644 EP 651 DI 10.1038/ng1790 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 048NW UT WOS:000237954800017 PM 16648850 ER PT J AU Pe'er, I de Bakker, PIW Maller, J Yelensky, R Altshuler, D Daly, MJ AF Pe'er, I de Bakker, PIW Maller, J Yelensky, R Altshuler, D Daly, MJ TI Evaluating and improving power in whole-genome association studies using fixed marker sets SO NATURE GENETICS LA English DT Article ID LINKAGE-DISEQUILIBRIUM; WIDE ASSOCIATION; COMPLEX TRAITS; TAGGING SNPS; DISEASE; POLYMORPHISM; MODELS; FUTURE; GENES; TESTS AB Emerging technologies make it possible for the first time to genotype hundreds of thousands of SNPs simultaneously, enabling whole-genome association studies. Using empirical genotype data from the International HapMap Project, we evaluate the extent to which the sets of SNPs contained on three whole-genome genotyping arrays capture common SNPs across the genome, and we find that the majority of common SNPs are well captured by these products either directly or through linkage disequilibrium. We explore analytical strategies that use HapMap data to improve power of association studies conducted with these fixed sets of markers and show that limited inclusion of specific haplotype tests in association analysis can increase the fraction of common variants captured by 25-100%. Finally, we introduce a Bayesian approach to association analysis by weighting the likelihood of each statistical test to reflect the number of putative causal alleles to which it is correlated. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM altshul@broad.mit.edu; mjdaly@chgr.mgh.harvard.edu RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009; OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Maller, Julian/0000-0002-1565-9559 NR 30 TC 203 Z9 206 U1 0 U2 5 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 2006 VL 38 IS 6 BP 663 EP 667 DI 10.1038/ng1816 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 048NW UT WOS:000237954800020 PM 16715096 ER PT J AU Sayer, JA Otto, EA O'Toole, JF Nurnberg, G Kennedy, MA Becker, C Hennies, HC Helou, J Attanasio, M Fausett, BV Utsch, B Khanna, H Liu, Y Drummond, I Kawakami, I Kusakabe, T Tsuda, M Ma, L Lee, H Larson, RG Allen, SJ Wilkinson, CJ Nigg, EA Shou, CC Lillo, C Williams, DS Hoppe, B Kemper, MJ Neuhaus, T Parisi, MA Glass, IA Petry, M Kispert, A Gloy, J Ganner, A Walz, G Zhu, XL Goldman, D Nurnberg, P Swaroop, A Leroux, MR Hildebrandt, F AF Sayer, JA Otto, EA O'Toole, JF Nurnberg, G Kennedy, MA Becker, C Hennies, HC Helou, J Attanasio, M Fausett, BV Utsch, B Khanna, H Liu, Y Drummond, I Kawakami, I Kusakabe, T Tsuda, M Ma, L Lee, H Larson, RG Allen, SJ Wilkinson, CJ Nigg, EA Shou, CC Lillo, C Williams, DS Hoppe, B Kemper, MJ Neuhaus, T Parisi, MA Glass, IA Petry, M Kispert, A Gloy, J Ganner, A Walz, G Zhu, XL Goldman, D Nurnberg, P Swaroop, A Leroux, MR Hildebrandt, F TI The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4 SO NATURE GENETICS LA English DT Article ID PRIMARY CILIA; RETINITIS-PIGMENTOSA; DOMAIN PROTEIN; NEPHRONOPHTHISIS; GENE; INVERSIN; MUTATIONS; INTERACTS; ENCODES; DISEASE AB The molecular basis of nephronophthisis(1), the most frequent genetic cause of renal failure in children and young adults, and its association with retinal degeneration and cerebellar vermis aplasia in Joubert syndrome(2) are poorly understood. Using positional cloning, we here identify mutations in the gene CEP290 as causing nephronophthisis. It encodes a protein with several domains also present in CENPF, a protein involved in chromosome segregation. CEP290 ( also known as NPHP6) interacts with and modulates the activity of ATF4, a transcription factor implicated in cAMP-dependent renal cyst formation. NPHP6 is found at centrosomes and in the nucleus of renal epithelial cells in a cell cycle-dependent manner and in connecting cilia of photoreceptors. Abrogation of its function in zebrafish recapitulates the renal, retinal and cerebellar phenotypes of Joubert syndrome. Our findings help establish the link between centrosome function, tissue architecture and transcriptional control in the pathogenesis of cystic kidney disease, retinal degeneration, and central nervous system development. C1 Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. Univ Newcastle Upon Tyne, Sch Clin Med Sci, Inst Human Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. Univ Cologne, Cologne Ctr Genom, D-5000 Cologne, Germany. RZPD Deutsch Ressourcectr Genomforsch, Berlin, Germany. Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. Univ Michigan, Inst Biol Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Ophthalmol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. Max Planck Inst Biochem, Dept Cell Biol, D-82152 Martinsried, Germany. Peking Univ, Sch Oncol, Beijing Inst Canc Res, Dept Biochem & Mol Biol, Beijing 100036, Peoples R China. Univ Calif San Diego, Sch Med, Dept Pharmacol & Neurosci, La Jolla, CA 92093 USA. Univ Cologne, Dept Pediat, D-5000 Cologne 41, Germany. Univ Zurich, Dept Pediat, CH-8006 Zurich, Switzerland. Univ Washington, Dept Pediat, Seattle, WA 98105 USA. Hannover Med Sch, Inst Mol Biol, D-30625 Hannover, Germany. Univ Cologne, Inst Genet, D-5000 Cologne 41, Germany. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Hildebrandt, F (reprint author), Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. EM fhilde@umich.edu RI Lillo, Concepcion/A-6321-2009; Kusakabe, Takehiro/H-7178-2012; OI Utsch, Boris/0000-0003-4623-581X; nigg, erich/0000-0003-4835-5719; Lillo, Concepcion/0000-0001-5814-9826; Kusakabe, Takehiro/0000-0002-8325-3665; Wilkinson, Christopher/0000-0002-7448-0938; Otto, Edgar/0000-0002-2387-9973; Sayer, John/0000-0003-1881-3782; Swaroop, Anand/0000-0002-1975-1141 FU NEI NIH HHS [EY07003, EY07961, EY13408, R01 EY007042, R01 EY007042-20]; NIDDK NIH HHS [DK064614, DK1068306, DK1069274, DK53093] NR 30 TC 305 Z9 315 U1 3 U2 20 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 2006 VL 38 IS 6 BP 674 EP 681 DI 10.1038/ng1786 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 048NW UT WOS:000237954800022 PM 16682973 ER PT J AU Purton, LE Scadden, DT AF Purton, LE Scadden, DT TI Osteoclasts eat stem cells out of house and home SO NATURE MEDICINE LA English DT Editorial Material ID HEMATOPOIETIC STEM; BONE-MARROW; MOBILIZATION; NICHE; LOCALIZATION; ENGRAFTMENT; MIGRATION; SIGNALS; MICE C1 Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Harvard Univ, Stem Cell Inst, Boston, MA 02114 USA. RP Purton, LE (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM scadden.david@mgh.harvard.edu NR 15 TC 14 Z9 14 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 2006 VL 12 IS 6 BP 610 EP 611 DI 10.1038/nm0606-610 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 051GI UT WOS:000238149200015 PM 16761001 ER PT J AU Venkatesha, S Toporsian, M Lam, C Hanai, J Mammoto, T Kim, YM Bdolah, Y Lim, KH Yuan, HT Libermann, TA Stillman, IE Roberts, D D'Amore, PA Epstein, FH Sellke, FW Romero, R Sukhatme, VP Letarte, M Karumanchi, SA AF Venkatesha, S Toporsian, M Lam, C Hanai, J Mammoto, T Kim, YM Bdolah, Y Lim, KH Yuan, HT Libermann, TA Stillman, IE Roberts, D D'Amore, PA Epstein, FH Sellke, FW Romero, R Sukhatme, VP Letarte, M Karumanchi, SA TI Soluble endoglin contributes to the pathogenesis of preeclampsia SO NATURE MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; HEREDITARY HEMORRHAGIC TELANGIECTASIA; PREGNANCY-INDUCED HYPERTENSION; ELEVATED LIVER-ENZYMES; BETA BINDING-PROTEIN; HUMAN CYTOTROPHOBLASTS; ENDOVASCULAR INVASION; CELLS; PLASMA AB Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Maternal endothelial dysfunction mediated by excess placenta-derived soluble VEGF receptor 1 ( sVEGFR1 or sFlt1) is emerging as a prominent component in disease pathogenesis. We report a novel placenta-derived soluble TGF-beta coreceptor, endoglin ( sEng), which is elevated in the sera of preeclamptic individuals, correlates with disease severity and falls after delivery. sEng inhibits formation of capillary tubes in vitro and induces vascular permeability and hypertension in vivo. Its effects in pregnant rats are amplified by coadministration of sFlt1, leading to severe preeclampsia including the HELLP ( hemolysis, elevated liver enzymes, low platelets) syndrome and restriction of fetal growth. sEng impairs binding of TGF-beta 1 to its receptors and downstream signaling including effects on activation of eNOS and vasodilation, suggesting that sEng leads to dysregulated TGF-beta signaling in the vasculature. Our results suggest that sEng may act in concert with sFlt1 to induce severe preeclampsia. C1 Beth Israel Deaconess Med Ctr, Dept Med, Ctr Vasc Biol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Ctr Vasc Biol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Ctr Vasc Biol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Ctr Vasc Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Hosp Sick Children, Canc Res Program, Toronto, ON M5G 1X8, Canada. Univ Toronto, Heart & Stroke Fdn, Richard Lewar Ctr Excellence, Toronto, ON M5G 1X8, Canada. NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Detroit, MI 48201 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA 02114 USA. RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Ctr Vasc Biol, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179; Toporsian, Mourad/0000-0002-8430-2094 FU NHLBI NIH HHS [HL079594]; NIDDK NIH HHS [DK064255] NR 51 TC 821 Z9 859 U1 7 U2 43 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 2006 VL 12 IS 6 BP 642 EP 649 DI 10.1038/nm1429 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 051GI UT WOS:000238149200025 PM 16751767 ER PT J AU Siegel, JM AF Siegel, JM TI The stuff dreams are made of: anatomical substrates of REM sleep SO NATURE NEUROSCIENCE LA English DT Editorial Material ID PARADOXICAL SLEEP; NEURONS; MEDULLA; NARCOLEPSY C1 Univ Calif Los Angeles, Sch Med, Ctr Sleep Res,Dept Psychiat, Vet Affairs Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, North Hills, CA 91343 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Sch Med, Ctr Sleep Res,Dept Psychiat, Vet Affairs Greater Los Angeles Healthcare Syst, 16111 Plummer St,151A3, North Hills, CA 91343 USA. EM jsiegel@ucla.edu NR 15 TC 29 Z9 32 U1 0 U2 4 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 2006 VL 9 IS 6 BP 721 EP 722 DI 10.1038/nn0606-721 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 047RA UT WOS:000237895200006 PM 16732200 ER PT J AU Mizuguchi, R Kriks, S Cordes, R Gossler, A Ma, QF Goulding, M AF Mizuguchi, R Kriks, S Cordes, R Gossler, A Ma, QF Goulding, M TI Ascl1 and Gsh1/2 control inhibitory and excitatory cell fate in spinal sensory interneurons SO NATURE NEUROSCIENCE LA English DT Article ID NEURONAL DIFFERENTIATION; CORD; SPECIFICATION; GENE; LBX1; NEUROGENESIS; EXPRESSION; PATHWAY; MASH1; PRESENILIN-1 AB Sensory information from the periphery is integrated and transduced by excitatory and inhibitory interneurons in the dorsal spinal cord. Recent studies have identified a number of postmitotic factors that control the generation of these sensory interneurons. We show that Gsh1/2 and Ascl1 (Mash1), which are expressed in sensory interneuron progenitors, control the choice between excitatory and inhibitory cell fates in the developing mouse spinal cord. During the early phase of neurogenesis, Gsh1/2 and Ascl1 coordinately regulate the expression of Tlx3, which is a critical postmitotic determinant for dorsal glutamatergic sensory interneurons. However, at later developmental times, Ascl1 controls the expression of Ptf1a in dIL(A) progenitors to promote inhibitory neuron differentiation while at the same time upregulating Notch signaling to ensure the proper generation of dIL(B) excitatory neurons. We propose that this switch in Ascl1 function enables the cogeneration of inhibitory and excitatory sensory interneurons from a common pool of dorsal progenitors. C1 Scripps Res Inst, Mol Neurobiol Lab, La Jolla, CA 92037 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Hannover Med Sch, Inst Mol Biol, Hannover, Germany. RP Goulding, M (reprint author), Scripps Res Inst, Mol Neurobiol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM goulding@salk.edu NR 38 TC 100 Z9 101 U1 1 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 2006 VL 9 IS 6 BP 770 EP 778 DI 10.1038/nn1706 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 047RA UT WOS:000237895200017 PM 16715081 ER PT J AU Ogino, S Brahmandam, M Kawasaki, T Kirkner, GJ Loda, M Fuchs, CS AF Ogino, Shuji Brahmandam, Mohan Kawasaki, Takako Kirkner, Gregory J. Loda, Massimo Fuchs, Charles S. TI Combined analysis of COX-2 and p53 expressions reveals synergistic inverse correlations with microsatellite instability and CpG island methylator phenotype in colorectal cancer SO NEOPLASIA LA English DT Article DE colon cancer; cyclooxygenase-2; DNA methylation; MethyLight; TP53 ID DNA METHYLATION; CYCLOOXYGENASE-2 EXPRESSION; COLON-CANCER; TUMORS; MUTATION; GROWTH; HYPERMETHYLATION; INHIBITION; SURVIVAL; CELLS AB Cyclooxygenase-2 (COX-2) overexpression and mutations of p53 (a known COX-2 regulator) are inversely associated with microsatellite instability-high (MSI-H) and CpG island methylator phenotype ( CIMP), characterized by extensive promotermethylation, is associated with MSI-H. However, no studies have comprehensively examined interrelations between COX-2, p53, MSI, and CIMP. Using MethyLight, we measured DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16/INK4A), CRABP1, MLH1, and NEUROG1] in relatively unbiased samples of 751 colorectal cancer cases obtained from two large prospective cohorts; 115 (15%) tumors were CIMP-high (>= 4 of 5 methylated promoters), 251 (33%) were CIMP-low ( 1 to 3 methylated promoters), and the remaining 385 (51%) were CIMP-0 ( no methylated promoters). CIMP-high tumors were much less frequent in COX-2+/p53+ tumors (4.6%) than in COX-2(+)/p53(-) tumors (19%; P <.0001), COX-2(-)/p53(+) tumors (17%; P =.04), andCOX-2(-)/p53(-) tumors (28%; P <.0001). In addition, COX-2(+)/p53(+) tumors were significantly less common in MSI-H CIMP-high tumors (9.7%) than in non-MSI-H CIMP-low/CIMP-0 tumors (44-47%; P <.0001). In conclusion, COX-2 and p53 alterations were synergistically inversely correlated with both MSI-H and CIMP-high. Our data suggest that a combined analysis of COX-2 and p53 may be more useful for the molecular classification of colorectal cancer than either COX-2 or p53 analysis alone. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA087969, P01 CA55075-13, P01 CA87969-03, P01 CA055075] NR 48 TC 62 Z9 63 U1 0 U2 3 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JUN PY 2006 VL 8 IS 6 BP 458 EP 464 DI 10.1593/neo.06247 PG 7 WC Oncology SC Oncology GA 067DY UT WOS:000239283100004 PM 16820091 ER PT J AU Browne, SE Yang, LC DiMauro, JP Fuller, SW Licata, SC Beal, MF AF Browne, SE Yang, LC DiMauro, JP Fuller, SW Licata, SC Beal, MF TI Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal cord pathology in the G93A SOD1 mouse model of ALS SO NEUROBIOLOGY OF DISEASE LA English DT Article DE amyotrophic lateral sclerosis; ATP; brain; cerebral glucose metabolism; corticospinal tract; creatine; 2-deoxyglucose; motor neuron; motor neuron disease; spinal cord ID AMYOTROPHIC-LATERAL-SCLEROSIS; MITOCHONDRIAL ELECTRON-TRANSPORT; CU/ZN SUPEROXIDE-DISMUTASE; TRANSGENIC MOUSE; CREATINE-KINASE; MUTANT SOD1; FUNCTIONAL-ORGANIZATION; GLUCOSE-UTILIZATION; MOTONEURON DISEASE; ENERGY-METABOLISM AB Multiple cell death pathways are implicated in the etiology of amyotrophic lateral sclerosis (ALS), but the cause of the characteristic motor neuron degeneration remains unknown. To determine whether CNS metabolic defects are critical for ALS pathogenesis, we examined the temporal evolution of energetic defects in the G93A SOD1 mouse model of familial ALS. [C-14 1-2-deoxyglucose in vivo autoradiography in G93A mice showed that glucose utilization is impaired in components of the corticospinal and bulbospinal motor tracts prior to either pathologic or bioenergetic changes in the spinal cord. This was accompanied by significant depletions in cortical ATP content in presymptomatic mice, which was partially ameliorated by creatine administration. Findings suggest that bioenergetic defects are involved in the initial stages of mSOD1-induced toxicity in G93A mice and imply that the selective dysfunction and degeneration of spinal cord motor neurons in this model may be secondary to dysfunction within cerebral motor pathways. (c) 2006 Elsevier Inc. All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02111 USA. RP Browne, SE (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, 525 E 68th St,A-502, New York, NY 10021 USA. EM sub2001@med.cornell.edu NR 63 TC 69 Z9 71 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN PY 2006 VL 22 IS 3 BP 599 EP 610 DI 10.1016/j.nbd.2006.01.001 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 055PL UT WOS:000238462600015 PM 16616851 ER PT J AU Napadow, V Kettner, N Ryan, A Kwong, KK Audette, J Hui, KKS AF Napadow, V Kettner, N Ryan, A Kwong, KK Audette, J Hui, KKS TI Somatosensory cortical plasticity in carpal tunnel syndrome - A cross-sectional fMRI evaluation SO NEUROIMAGE LA English DT Article DE soniatotopy; nerve entrapment; neuropathy; hebbian plasticity; disinhibition ID REGIONAL PAIN SYNDROME; ADULT OWL MONKEYS; TACTILE STIMULATION; MOTOR CORTEX; SOMATOTOPIC ORGANIZATION; ELECTRICAL-STIMULATION; COORDINATE SYSTEM; NERVE COMPRESSION; DIGIT AMPUTATION; CEREBRAL-CORTEX AB Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve characterized by paresthesias and pain in the first, second, and third digits. We hypothesize that aberrant afferent input in CTS will lead to cortical plasticity. Functional MRI (fMRI) and neurophysiological testing were performed on CTS patients and healthy adults. Median nerve innervated digit 2 (D2), and digit 3 (D3) and ulnar nerve innervated digit 5 (D5) were stimulated during fMRI. Surface-based and ROI-based analyses consistently demonstrated more extensive and stronger contralateral sensorimotor cortical representations of D2 and D3 for CTS patients as compared to healthy adults (P < 0.05). Differences were less profound for D5. Moreover, D3 fMRI activation in both the contralateral SI and motor cortex correlated positively with the D3 sensory conduction latency. Analysis of somatotopy suggested that contralateral SI representations for D2 and D3 were less separated for CTS patients (3.8 +/- 1.0 mm) than for healthy adults (7.5 +/- 1.2 mm). Furthermore, the D3/D2 separation distance correlated negatively with D2 sensory conduction latency-the greater the latency, the closer the D2/D3 cortical representations (r = 0.79, P < 0.05). Coupled with a greater extent of SI representation for these CTS affected digits, the closer cortical representations can be interpreted as a blurred somatotopic arrangement for CTS affected digits. These findings provide further evidence that CTS is not manifest in the periphery alone. Our results are consistent with Hebbian plasticity mechanisms, as our cohort of CTS patients had predominant paresthesias, which produce more temporally coherent afferent signaling from affected digits. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. Spaulding Rehabil Hosp, Boston, MA USA. RP Napadow, V (reprint author), 149 13th St Rm 2301, Charlestown, MA 02119 USA. EM vitaly@nmr.mgh.harvard.edu FU NCCIH NIH HHS [K01-AT002166-01, P01-AT002048-02, R21-AT001361-01] NR 67 TC 53 Z9 54 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2006 VL 31 IS 2 BP 520 EP 530 DI 10.1016/j.neuroimaging.2005.12.017 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 052KH UT WOS:000238232100007 PM 16460960 ER PT J AU Britton, JC Taylor, SF Sudheimer, KD Liberzon, I AF Britton, JC Taylor, SF Sudheimer, KD Liberzon, I TI Facial expressions and complex IAPS pictures: Common and differential networks SO NEUROIMAGE LA English DT Article ID MEDIAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; HUMAN AMYGDALA; NEURAL ACTIVATION; EMOTIONAL RESPONSES; POSITIVE EMOTIONS; NEGATIVE AFFECT; NEUTRAL FACES; BUILD THEORY; FMRI AB Neuroimaging studies investigating emotion have commonly used two different visual stimulus formats, facial expressions of emotion or emotionally evocative scenes. However, it remains an important unanswered question whether or not these different stimulus formats entail the same processes. Facial expressions of emotion may elicit more emotion recognition/perception, and evocative pictures may elicit more direct experience of emotion. In spite of these differences, common areas of activation have been reported across different studies, but little work has investigated activations in response to the two stimulus formats in the same subjects. In this fMRI study, we compared BOLD activation patterns to facial expression of emotions and to complex emotional pictures from the International Affective Picture System (IAPS) to determine if these stimuli would activate similar or distinct brain regions. Healthy volunteers passively viewed blocks of expressive faces and IAPS pictures balanced for specific emotion (happy, sad, anger, fear, neutral), interleaved with blocks of fixation. Eye movement, reaction times, and off-line subjective ratings including discrete emotion, valence, and arousal were also recorded. Both faces and IAPS pictures activated similar structures, including the amygdala, posterior hippocampus, ventromedial prefrontal cortex, and visual cortex. In addition, expressive faces uniquely activated the superior temporal gyros, insula, and anterior cingulate more than IAPS pictures, despite the faces being less arousing. For the most part, these regions were activated in response to all specific emotions; however, some regions responded only to a subset. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Michigan, Dept Neurosci, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Vet Adm Med Ctr, Psychiat Serv, Ann Arbor, MI 48105 USA. RP Britton, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149 13th St, Charlestown, MA 02129 USA. EM jbritton@nmr.mgh.harvard.edu RI Taylor, Stephan/A-1211-2007; Britton, Jennifer/J-4501-2013; OI Liberzon, Israel/0000-0002-4990-556X FU NIMH NIH HHS [F31MH069003] NR 89 TC 218 Z9 226 U1 11 U2 52 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 JUN PY 2006 VL 31 IS 2 BP 906 EP 919 DI 10.1016/j.neuroimage.2005.12.050 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 052KH UT WOS:000238232100044 PM 16488159 ER PT J AU Anderson, CM Maas, LC Frederick, BD Bendor, JT Spencer, TJ Livni, E Lukas, SE Fischman, AJ Madras, BK Renshaw, PF Kaufman, MJ AF Anderson, CM Maas, LC Frederick, BD Bendor, JT Spencer, TJ Livni, E Lukas, SE Fischman, AJ Madras, BK Renshaw, PF Kaufman, MJ TI Cerebellar vermis involvement in cocaine-related behaviors SO NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 67th Annual Scientific Meeting of the College-on-Problems-of-Drug-Dependence CY 2005 CL Quebec City, CANADA SP Coll Problems Drug Dependence DE cocaine; stimulants; cerebellum; vermis; dopamine transporter; craving ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; TRANSPORTER-IMMUNOREACTIVE AXONS; STRIATAL DOPAMINE TRANSPORTER; VENTRAL TEGMENTAL AREA; BRAIN ACTIVATION; PREFRONTAL CORTEX; WORKING-MEMORY; NOREPINEPHRINE TRANSPORTER; PARKINSONS-DISEASE AB Although the cerebellum is increasingly being viewed as a brain area involved in cognition, it typically is excluded from circuitry considered to mediate stimulant-associated behaviors since it is low in dopamine. Yet, the primate cerebellar vermis (lobules II-III and VIII-IX) has been reported to contain axonal dopamine transporter immunoreactivity (DAT-IR). We hypothesized that DAT-IR-containing vermis areas would be activated in cocaine abusers by cocaine-related cues and, in healthy humans, would accumulate DAT-selective ligands. We used BOLD fMRI to determine whether cocaine-related cues activated DAT-IR-enriched vermis regions in cocaine abusers and positron emission tomography imaging of healthy humans to determine whether the DAT-selective ligand [C-11] altropane accumulated in those vermis regions. Cocaine-related cues selectively induced BOLD activation in lobules II-III and VIII-IX in cocaine users, and, at early time points after ligand administration, we found appreciable [C-11] altropane accumulation in lobules VIII-IX, possibly indicating DAT presence in this region. These data suggest that parts of cerebellar vermis mediate cocaine's persisting and acute effects. In light of prior findings illustrating vermis connections to midbrain dopamine cell body regions, established roles for the vermis as a locus of sensorimotor integration and motor planning, and findings of increased vermis activation in substance abusers during reward-related and other cognitive tasks, we propose that the vermis be considered one of the structures involved in cocaine- and other incentive-related behaviors. C1 Harvard Univ, Brain Imaging Ctr, McLean Hosp, Sch Med, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Div Neurochem, Dept Psychiat,New England Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat,Behav Psychopharmacol Res Lab, Belmont, MA 02178 USA. RP Kaufman, MJ (reprint author), Harvard Univ, Brain Imaging Ctr, McLean Hosp, Sch Med, 115 Mill St, Belmont, MA 02478 USA. EM kaufman@mclean.harvard.edu RI Frederick, Blaise/G-6098-2012; OI Frederick, Blaise/0000-0001-5832-5279; Bendor, Jacob/0000-0003-1455-4891 FU NCRR NIH HHS [RR000168]; NIDA NIH HHS [DA00343, DA006303, DA009448, DA014178, DA014674, DA015116, DA015305, DA016222, DA017324, DA03994, DA14013, DA16746]; NIMH NIH HHS [MH31862]; NINDS NIH HHS [NS31862] NR 76 TC 50 Z9 51 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2006 VL 31 IS 6 BP 1318 EP 1326 DI 10.1038/sj.npp.1300937 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 047SS UT WOS:000237899600020 PM 16237382 ER PT J AU Stein, PD Fowler, SE Goodman, LR Gottschalk, A Hales, CA Hull, RD Leeper, KV Popovich, J Quinn, DA Sos, TA Sostman, HD Tapson, VF Wakefield, TW Weg, JG Woodard, PK AF Stein, PD Fowler, SE Goodman, LR Gottschalk, A Hales, CA Hull, RD Leeper, KV Popovich, J Quinn, DA Sos, TA Sostman, HD Tapson, VF Wakefield, TW Weg, JG Woodard, PK CA PIOPED II Investigators TI Multidetector computed tomography for acute pulmonary embolism SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ROW SPIRAL CT; D-DIMER; LUNG-SCAN; THROMBOEMBOLIC DISEASE; VENOUS THROMBOSIS; CLINICAL-MODEL; HELICAL CT; ANGIOGRAPHY; DIAGNOSIS; VENOGRAPHY AB Background: The accuracy of multidetector computed tomographic angiography (CTA) for the diagnosis of acute pulmonary embolism has not been determined conclusively. Methods: The Prospective Investigation of Pulmonary Embolism Diagnosis II trial was a prospective, multicenter investigation of the accuracy of multidetector CTA alone and combined with venous-phase imaging (CTA-CTV) for the diagnosis of acute pulmonary embolism. We used a composite reference test to confirm or rule out the diagnosis of pulmonary embolism. Results: Among 824 patients with a reference diagnosis and a completed CT study, CTA was inconclusive in 51 because of poor image quality. Excluding such inconclusive studies, the sensitivity of CTA was 83 percent and the specificity was 96 percent. Positive predictive values were 96 percent with a concordantly high or low probability on clinical assessment, 92 percent with an intermediate probability on clinical assessment, and nondiagnostic if clinical probability was discordant. CTA-CTV was inconclusive in 87 of 824 patients because the image quality of either CTA or CTV was poor. The sensitivity of CTA-CTV for pulmonary embolism was 90 percent, and specificity was 95 percent. CTA-CTV was also nondiagnostic with a discordant clinical probability. Conclusions: In patients with suspected pulmonary embolism, multidetector CTA-CTV has a higher diagnostic sensitivity than does CTA alone, with similar specificity. The predictive value of either CTA or CTA-CTV is high with a concordant clinical assessment, but additional testing is necessary when the clinical probability is inconsistent with the imaging results. C1 St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI 48341 USA. Wayne State Univ, Dept Med, Detroit, MI 48202 USA. George Washington Univ, Dept Epidemiol & Biostat, Ctr Biostat, Rockville, MD USA. Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. Michigan State Univ, Dept Radiol, E Lansing, MI 48824 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calgary, Dept Med, Calgary, AB, Canada. Emory Univ, Dept Med, Atlanta, GA 30322 USA. Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. Weill Cornell Med Coll, Dept Radiol, New York, NY USA. Weill Cornell Med Coll, Houston, TX USA. Methodist Hosp, Houston, TX 77030 USA. Duke Univ, Dept Med, Durham, NC USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Washington Univ, Dept Radiol, St Louis, MO 63130 USA. RP Stein, PD (reprint author), St Joseph Mercy Oakland Hosp, Dept Res, 44405 Woodward Ave, Pontiac, MI 48341 USA. EM steinp@trinity-health.org FU NHLBI NIH HHS [HL63940, HL063932, HL63899, HL63928, HL63931, HL63941, HL63942, HL63981, HL63982, HL67453] NR 40 TC 710 Z9 769 U1 4 U2 13 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 JUN 1 PY 2006 VL 354 IS 22 BP 2317 EP U7 DI 10.1056/NEJMoa052367 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 047ZZ UT WOS:000237918500004 PM 16738268 ER PT J AU Jacobson, BC Somers, SC Fuchs, CS Kelly, CP Camargo, CA AF Jacobson, BC Somers, SC Fuchs, CS Kelly, CP Camargo, CA TI Body-mass index and symptoms of gastroesophageal reflux in women SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RISK-FACTORS; EROSIVE ESOPHAGITIS; UNITED-STATES; DISEASE; POPULATION; OBESITY; PREVALENCE; ADENOCARCINOMA; QUESTIONNAIRE; HEARTBURN AB Background: Overweight and obese persons are at increased risk for gastroesophageal reflux disease. An association between body-mass index (BMI) -- the weight in kilograms divided by the square of the height in meters -- and symptoms of gastroesophageal reflux disease in persons of normal weight has not been demonstrated. Methods: In 2000, we used a supplemental questionnaire to determine the frequency, severity, and duration of symptoms of gastroesophageal reflux disease among randomly selected participants in the Nurses' Health Study. After categorizing women according to BMI as measured in 1998, we used logistic-regression models to study the association between BMI and symptoms of gastroesophageal reflux disease. Results: Of 10,545 women who completed the questionnaire (response rate, 86 percent), 2310 (22 percent) reported having symptoms at least once a week, and 3419 (55 percent of those who had any symptoms) described their symptoms as moderate in severity. We observed a dose-dependent relationship between increasing BMI and frequent reflux symptoms (multivariate P for trend <0.001). As compared with women who had a BMI of 20.0 to 22.4, the multivariate odds ratios for frequent symptoms were 0.67 (95 percent confidence interval, 0.48 to 0.93) for a BMI of less than 20.0, 1.38 (95 percent confidence interval, 1.13 to 1.67) for a BMI of 22.5 to 24.9, 2.20 (95 percent confidence interval, 1.81 to 2.66) for a BMI of 25.0 to 27.4, 2.43 (95 percent confidence interval, 1.96 to 3.01) for a BMI of 27.5 to 29.9, 2.92 (95 percent confidence interval, 2.35 to 3.62) for a BMI of 30.0 to 34.9, and 2.93 (95 percent confidence interval, 2.24 to 3.85) for a BMI of 35.0 or more. Even in women with a normal baseline BMI, an increase in BMI of more than 3.5, as compared with no weight changes, was associated with an increased risk of frequent symptoms of reflux (odds ratio, 2.80; 95 percent confidence interval, 1.63 to 4.82). Conclusions: BMI is associated with symptoms of gastroesophageal reflux disease in both normal-weight and overweight women. Even moderate weight gain among persons of normal weight may cause or exacerbate symptoms of reflux. C1 Boston Univ, Med Ctr, Sch Med, Boston, MA 02118 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jacobson, BC (reprint author), Boston Univ, Med Ctr, Sch Med, 85 E Concord St,Rm 7721, Boston, MA 02118 USA. EM brian.jacobson@bmc.org FU NIAID NIH HHS [R21 AI-52338, R21 AI052338]; NIDDK NIH HHS [K08 DK070706, K08 DK070706-02] NR 25 TC 247 Z9 258 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 JUN 1 PY 2006 VL 354 IS 22 BP 2340 EP U18 DI 10.1056/NEJMoa054391 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 047ZZ UT WOS:000237918500006 PM 16738270 ER PT J AU Buys, ES Jassal, DS Neilan, TG Raher, MJ Ichinose, F Janssens, S Picard, MH Bloch, KD Scherrer-Crosbie, M AF Buys, Emmanuel S. Jassal, Davinder S. Neilan, Tom G. Raher, Michael J. Ichinose, Fumito Janssens, Stefan Picard, Michael H. Bloch, Kenneth D. Scherrer-Crosbie, Marielle TI Cardiomyocyte-specific overexpression of nitric oxide synthase 3 improves left ventricular remodeling in mice with chronic pressure overload SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th International Conference on Biology, Chemistry and Therapeutic Applications of Nitric Oxide CY JUN 25-29, 2006 CL Monterey, CA SP NitroMed Inc, INO Therapeut, Ajinomoto AminoSci LLC, Bayer HealthCare, BioMarin Pharmaceut Inc, Nitr Oxide Soc Japan, Pfizer Inc, Schering AG, ALEXIS Biochem, Altana Pharma AG, BioLegend Ing, BIOMOL Int LP, Boehringer Ingelheim, Cognosci Inc, ECO PHYS INC, Med Coll Georgia C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Katholieke Univ Leuven VIB, Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD JUN PY 2006 VL 14 IS 4 BP A61 EP A62 DI 10.1016/j.niox.2006.04.201 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 054TC UT WOS:000238400500190 ER PT J AU Cauwels, A Janssen, B Buys, E Sips, P Brouckaert, P AF Cauwels, A Janssen, B Buys, E Sips, P Brouckaert, P TI Anaphylactic shock depends on PI3K, Akt and eNOS-derived NO SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th International Conference on Biology, Chemistry and Therapeutic Applications of Nitric Oxide CY JUN 25-29, 2006 CL Monterey, CA SP NitroMed Inc, INO Therapeut, Ajinomoto AminoSci LLC, Bayer HealthCare, BioMarin Pharmaceut Inc, Nitr Oxide Soc Japan, Pfizer Inc, Schering AG, ALEXIS Biochem, Altana Pharma AG, BioLegend Ing, BIOMOL Int LP, Boehringer Ingelheim, Cognosci Inc, ECO PHYS INC, Med Coll Georgia C1 Univ Ghent, Dept Mol Biomed Res, B-9000 Ghent, Belgium. Univ Maastricht, Maastricht, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD JUN PY 2006 VL 14 IS 4 BP A52 EP A52 DI 10.1016/j.niox.2006.04.174 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 054TC UT WOS:000238400500164 ER PT J AU Ichinose, F Buys, ES Bloch, KD AF Ichinose, F Buys, ES Bloch, KD TI Cardiomyocyte-specific overexpression of NOS3 prevents myocardial dysfunction in routine models of septic shock SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th International Conference on Biology, Chemistry and Therapeutic Applications of Nitric Oxide CY JUN 25-29, 2006 CL Monterey, CA SP NitroMed Inc, INO Therapeut, Ajinomoto AminoSci LLC, Bayer HealthCare, BioMarin Pharmaceut Inc, Nitr Oxide Soc Japan, Pfizer Inc, Schering AG, ALEXIS Biochem, Altana Pharma AG, BioLegend Ing, BIOMOL Int LP, Boehringer Ingelheim, Cognosci Inc, ECO PHYS INC, Med Coll Georgia C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD JUN PY 2006 VL 14 IS 4 BP A60 EP A61 DI 10.1016/j.niox.2006.04.198 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 054TC UT WOS:000238400500187 ER PT J AU Sips, PY Buys, E Rogge, E Nimmegeers, S Dewerchin, M Van de Voorde, J Brouckaert, P AF Sips, Patrick Yves Buys, Emmanuel Rogge, Elke Nimmegeers, Sofie Dewerchin, Mieke Van de Voorde, Johan Brouckaert, Peter TI Functional knockout of the soluble guanylate cyclase alpha 1 subunit leads to gender-specific hypertension while retaining sensitivity to nitric oxide SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th International Conference on Biology, Chemistry and Therapeutic Applications of Nitric Oxide CY JUN 25-29, 2006 CL Monterey, CA SP NitroMed Inc, INO Therapeut, Ajinomoto AminoSci LLC, Bayer HealthCare, BioMarin Pharmaceut Inc, Nitr Oxide Soc Japan, Pfizer Inc, Schering AG, ALEXIS Biochem, Altana Pharma AG, BioLegend Ing, BIOMOL Int LP, Boehringer Ingelheim, Cognosci Inc, ECO PHYS INC, Med Coll Georgia C1 Univ Ghent VIB, Dept Mol Biomed Res, B-9000 Ghent, Belgium. Massachusetts Gen Hosp, Boston, MA 02114 USA. Catholic Univ Louvain VIB, B-3000 Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD JUN PY 2006 VL 14 IS 4 BP A4 EP A5 DI 10.1016/j.niox.2006.04.018 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 054TC UT WOS:000238400500021 ER PT J AU Yu, BL Ichinose, F Bloch, KD Zapol, WM AF Yu, BL Ichinose, F Bloch, KD Zapol, WM TI Congenital nitric oxide synthase 3 (NOS3) deficiency prevents the systemic hypertensive reaction to tetrameric hemoglobin infusion SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 4th International Conference on Biology, Chemistry and Therapeutic Applications of Nitric Oxide CY JUN 25-29, 2006 CL Monterey, CA SP NitroMed Inc, INO Therapeut, Ajinomoto AminoSci LLC, Bayer HealthCare, BioMarin Pharmaceut Inc, Nitr Oxide Soc Japan, Pfizer Inc, Schering AG, ALEXIS Biochem, Altana Pharma AG, BioLegend Ing, BIOMOL Int LP, Boehringer Ingelheim, Cognosci Inc, ECO PHYS INC, Med Coll Georgia C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD JUN PY 2006 VL 14 IS 4 BP A59 EP A60 DI 10.1016/j.niox.2006.04.195 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 054TC UT WOS:000238400500184 ER PT J AU Brooksbank, C Quackenbush, J AF Brooksbank, Cath Quackenbush, John TI Data standards: A call to action SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID BIOLOGY MARKUP LANGUAGE; MINIMUM INFORMATION; MICROARRAY DATA; MODELS AB Access to data is something that every molecular biologist takes for granted nowadays, but data alone is of little use unless it is made available in a useable form through the development and global uptake of data standards. The challenge of standards development has been taken up by grass-roots movements working within several different branches of the biomedical research community. Many of these initiatives are proving extremely successful; for example, the Gene Ontology, which provides a controlled vocabulary for describing the properties of gene products, the Microarray Gene Expression Data Society's standards for describing microarray experiments, and the emerging standards developed by the Proteomics Standards Initiative are gaining broad acceptance. Standards development now faces its greatest ever challenge-the integration of diverse data types to fulfill the goals of systems biology. Now is the time for the communities that are developing these standards, the funding bodies that have invested so heavily in high-throughput data generation, and the publishers of biomedical research papers to cooperate fully to make the goals of integrated data analysis a reality. This paper is part of the special issue of OMICS on data standards. C1 European Bioinformat Inst, EMBL, Cambridge CB2 6SA, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Brooksbank, C (reprint author), European Bioinformat Inst, EMBL, Cambridge CB2 6SA, England. EM cath@ebi.ac.uk OI Brooksbank, Catherine/0000-0001-9395-7001 NR 15 TC 31 Z9 31 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD JUN PY 2006 VL 10 IS 2 BP 94 EP 99 DI 10.1089/omi.2006.10.94 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 079XJ UT WOS:000240210900002 PM 16901212 ER PT J AU Whetzel, PL Brinkman, RR Causton, HC Fan, L Field, D Fostel, J Fragoso, G Gray, T Heiskanen, M Hernandez-Boussard, T Morrison, N Parkinson, H Rocca-Serra, P Sansone, SA Schober, D Smith, B Stevens, R Stoeckert, CJ Taylor, C White, J Wood, A AF Whetzel, Patricia L. Brinkman, Ryan R. Causton, Helen C. Fan, Liju Field, Dawn Fostel, Jennifer Fragoso, Gilberto Gray, Tanya Heiskanen, Mervi Hernandez-Boussard, Tina Morrison, Norman Parkinson, Helen Rocca-Serra, Philippe Sansone, Susanna-Assunta Schober, Daniel Smith, Barry Stevens, Robert Stoeckert, Christian J. Taylor, Chris White, Joe Wood, Andrew CA FuGO Working Grp TI Development of FuGO: An ontology for Functional Genomics Investigations SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article AB The development of the Functional Genomics Investigation Ontology (FuGO) is a collaborative, international effort that will provide a resource for annotating functional genomics investigations, including the study design, protocols and instrumentation used, the data generated and the types of analysis performed on the data. FuGO will contain both terms that are universal to all functional genomics investigations and those that are domain specific. In this way, the ontology will serve as the "semantic glue" to provide a common understanding of data from across these disparate data sources. In addition, FuGO will reference out to existing mature ontologies to avoid the need to duplicate these resources, and will do so in such a way as to enable their ease of use in annotation. This project is in the early stages of development; the paper will describe efforts to initiate the project, the scope and organization of the project, the work accomplished to date, and the challenges encountered, as well as future plans. This paper is part of the special issue of OMICS on data standards. C1 Univ Penn, Sch Med, Ctr Bioinformat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC, Ctr Clin Sci, London, England. Ontol Workshop LLC, Columbia, MD USA. Oxford Ctr Ecol & Hydrol, Mol Evolut & Bioinformat Sect, Oxford, England. NIEHS, Res Triangle Pk, NC 27709 USA. NCI, Ctr Bioinformat, NCICB, Rockville, MD USA. Stanford Univ, Med Ctr, Dept Genet, Stanford, CA 94305 USA. Univ Manchester, Dept Comp Sci, Manchester, Lancs, England. Oxford Ctr Ecol & Hydrol, NERC, Environm Bioinformat Ctr, Oxford, England. European Bioinformat Inst, Cambridge, England. SUNY Buffalo, Dept Philosophy, Ctr Excellence Bioinformat & Life Sci, Buffalo, NY USA. SUNY Buffalo, Natl Ctr Biomed Oncol, Buffalo, NY USA. Inst Formal Ontol & Med Sci, Saarbrucken, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Whetzel, PL (reprint author), Univ Penn, Sch Med, Ctr Bioinformat, Philadelphia, PA 19104 USA. EM whetzel@pcbi.upenn.edu RI Field, Dawn/C-1653-2010; Brinkman, Ryan/B-1108-2008; Smith, Barry/A-9525-2011; OI Brinkman, Ryan/0000-0002-9765-2990; Smith, Barry/0000-0003-1384-116X; Sansone, Susanna-Assunta/0000-0001-5306-5690 FU Intramural NIH HHS; NHGRI NIH HHS [1 U 54 HG004028, P41 HG003619, P41 HG003619-01]; NIBIB NIH HHS [R01 EB005034-02, EB-5034, R01 EB005034]; NIGMS NIH HHS [U01 GM061374, U01GM61374] NR 14 TC 35 Z9 36 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD JUN PY 2006 VL 10 IS 2 BP 199 EP 204 DI 10.1089/omi.2006.10.199 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 079XJ UT WOS:000240210900016 PM 16901226 ER PT J AU Deutsch, EW Ball, CA Bova, GS Brazma, A Bumgarner, RE Campbell, D Causton, HC Christiansen, J Davidson, D Eichner, LJ Goo, YA Grimmond, S Henrich, T Johnson, MH Korb, M Mills, JC Oudes, A Parkinson, HE Pascal, LE Quackenbush, J Ramialison, M Ringwald, M Sansone, SA Sherlock, G Stoeckert, CJ Swedlow, J Taylor, RC Walashek, L Zhou, Y Liu, AY True, LD AF Deutsch, Eric W. Ball, Catherine A. Bova, G. Steven Brazma, Alvis Bumgarner, Roger E. Campbell, David Causton, Helen C. Christiansen, Jeff Davidson, Duncan Eichner, Lillian J. Goo, Young Ah Grimmond, Sean Henrich, Thorsten Johnson, Michael H. Korb, Martin Mills, Jason C. Oudes, Asa Parkinson, Helen E. Pascal, Laura E. Quackenbush, John Ramialison, Mirana Ringwald, Martin Sansone, Susanna-A. Sherlock, Gavin Stoeckert, Christian J., Jr. Swedlow, Jason Taylor, Ronald C. Walashek, Laura Zhou, Yi Liu, Alvin Y. True, Lawrence D. TI Development of the Minimum Information Specification for in situ Hybridization and Immunohistochemistry Experiments (MISFISHIE) SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article AB We describe the creation process of the Minimum Information Specification for In Situ Hybridization and Immunohistochemistry Experiments (MISFISHIE). Modeled after the existing minimum information specification for microarray data, we created a new specification for gene expression localization experiments, initially to facilitate data sharing within a consortium. After successful use within the consortium, the specification was circulated to members of the wider biomedical research community for comment and refinement. After a period of acquiring many new suggested requirements, it was necessary to enter a final phase of excluding those requirements that were deemed inappropriate as a minimum requirement for all experiments. The full specification will soon be published as a version 1.0 proposal to the community, upon which a more full discussion must take place so that the final specification may be achieved with the involvement of the whole community. This paper is part of the special issue of OMICS on data standards. C1 Inst Syst Biol, Seattle, WA 98103 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Hlth Informat Sci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Med Genet, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD USA. EBI, EMBL, Cambridge, England. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Imperial Coll Sch Med Microarray Ctr, CSC, London, England. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia. EMBL Heidelberg, Heidelberg, Germany. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Univ Penn, Ctr Bioinformat, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Univ Dundee, Wellcome Trust Bioctr, Div Gene Regulat & Express, Dundee, Scotland. Pacific NW Natl Lab, Richland, WA 99352 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Deutsch, EW (reprint author), Inst Syst Biol, 1441 N 34th St, Seattle, WA 98103 USA. EM edeutsch@systemsbiology.org RI Sherlock, Gavin/B-1831-2009; Sherlock, Gavin/E-9110-2012; Bumgarner, Roger/K-3531-2015; Grimmond, Sean/J-5304-2016; OI Bumgarner, Roger/0000-0002-8168-6985; Grimmond, Sean/0000-0002-8102-7998; Christiansen, Jeffrey/0000-0002-8146-1225; Sansone, Susanna-Assunta/0000-0001-5306-5690; Ramialison, Mirana/0000-0001-6315-4777 FU Medical Research Council [MC_U127527203]; NIDDK NIH HHS [1U01 DK63328, 1U01 DK63481, 1R01 DK63400, 1U01 DK63483, 1U01 DK63630] NR 8 TC 12 Z9 12 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD JUN PY 2006 VL 10 IS 2 BP 205 EP 208 DI 10.1089/omi.2006.10.205 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 079XJ UT WOS:000240210900017 PM 16901227 ER PT J AU LaCasce, AS AF LaCasce, Ann S. TI Post-transplant.lymphoproliferative disorders SO ONCOLOGIST LA English DT Article DE PTLD; early lesion; polymorphic PTLD; monomorphic PTLD ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; EPSTEIN-BARR-VIRUS; LUNG-TRANSPLANT RECIPIENTS; SERUM-PROTEIN ELECTROPHORESIS; SOLID-ORGAN TRANSPLANTATION; PROGNOSTIC-FACTORS; SINGLE-CENTER; LIVER-TRANSPLANTATION; VIRAL LOAD; DISEASE AB Post-transplant lymphoproliferative disorder is the most common malignancy, with the exception of skin cancer, after solid organ transplantation in adults. The incidence varies according to the transplanted organ and is often associated with Epstein-Barr virus. Prognosis is variable, due in part to the heterogeneity of the disease, which ranges from reactive plasmacytic hyperplasia to aggressive monoclonal disease. C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP LaCasce, AS (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM Ann_LaCasce@dcfi.harvard.edu NR 59 TC 47 Z9 48 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUN PY 2006 VL 11 IS 6 BP 674 EP 680 DI 10.1634/theoncologist.11-6-674 PG 7 WC Oncology SC Oncology GA 085TO UT WOS:000240627500013 PM 16794246 ER PT J AU Grier, JT Batchelor, T AF Grier, Jeanine T. Batchelor, Tracy TI Low-grade gliomas in adults SO ONCOLOGIST LA English DT Article DE low-grade glioma; astrocytoma; oligodendroglioma ID MAGNETIC-RESONANCE SPECTROSCOPY; BRAIN-STEM GLIOMAS; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; RADIATION-THERAPY; OLIGODENDROGLIAL TUMORS; TEMOZOLOMIDE CHEMOTHERAPY; MIXED OLIGOASTROCYTOMAS; EUROPEAN ORGANIZATION; STEREOTACTIC BIOPSY AB Low-grade gliomas are a heterogeneous group of neoplasms usually encountered in younger patient, populations. These tumors represent a unique challenge because most patients will survive a decade or more and may be at a higher risk for treatment-related complications. Clinical observations over the years have identified a subset of low-grade gliomas that tends to manifest more aggressive clinical behavior and require earlier, more aggressive intervention. Clinical and molecular parameters may allow better assessment of prognosis and application of risk-adjusted management strategies that may include resection, radiation, or chemotherapy. Improved methods of long-term cognitive and functional assessment are desperately needed in this patient population. C1 Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Div Neurooncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Batchelor, T (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Div Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org NR 98 TC 60 Z9 65 U1 3 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JUN PY 2006 VL 11 IS 6 BP 681 EP 693 DI 10.1634/theoncologist.11-6-681 PG 13 WC Oncology SC Oncology GA 085TO UT WOS:000240627500014 PM 16794247 ER PT J AU D'Amico, DJ AF D'Amico, Donald J. CA VISION Clinical Trial Grp TI Pegaptanib sodium for neovascular age-related macular degeneration - Two-year safety results of the two prospective, multicenter, controlled clinical trials SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 05, 2005 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID ENDOTHELIAL GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; PROLIFERATIVE DIABETIC-RETINOPATHY; PHASE-II TRIAL; NONHUMAN PRIMATE; IRIS NEOVASCULARIZATION; PHOTODYNAMIC THERAPY; FLUOROURACIL; LEUCOVORIN AB Objective: To evaluate the safety of pegaptanib sodium injection, a specific vascular endothelial growth factor (VEGF) antagonist, in the treatment of neovascular age-related macular degeneration (AMD) during 2 years of therapy. Design: Two concurrent, prospective, randomized, multicenter, double-masked, sham-controlled studies. Methods: Patients with all angiographic choroidal neovascularization lesion compositions of AMD received either intravitreous pegaptanib sodium (0.3 mg, 1 mg, 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks; sham-treated patients were re-randomized (1:1:1:1:1) to continue sham, discontinue, or receive one of the pegaptanib doses. Main Outcome Measures: All reported adverse events, serious adverse events, and deaths. Participants: In year 1, 1190 subjects received at least one study treatment (0.3 mg, n = 295; 1 mg, n = 301; 3 mg, n = 296; sham, n = 298); 7545 intravitreous injections of pegaptanib were administered. In year 2, 425 subjects (0.3 mg, n = 128; 1 mg, n = 126; 3 mg, n = 120; sham, n = 51) continued the same masked treatment as in year 1 and received at least one study treatment in year 2; 2663 intravitreous injections of pegaptanib were administered in these subjects. Results: All doses of pegaptanib were well tolerated. The most common ocular adverse events were transient, mild to moderate in intensity, and attributed to the injection preparation and procedure. There was no evidence of an increase in deaths, in events associated with systemic VEGF inhibition (e.g., hypertension, thromboembolic events, serious hemorrhagic events), or in severe ocular inflammation, cataract progression, or glaucoma in pegaptanib-treated patients relative to sham-treated patients. In year 1, serious injection-related complications included endophthalmitis (12 events, 0.16%/injection), retinal detachment (RD) (6 events [4 rhegmatogenous, 2 exudative], 0.08%/injection), and traumatic cataract (5 events, 0.07%/injection). Most cases of endophthalmitis followed violations of the injection preparation protocol. In patients receiving pegaptanib for > 1 year, there were no reports of endophthalmitis or traumatic cataract in year 2; RD was reported in 4 patients (all rhegmatogenous, 0.15%/injection). Conclusion: The 2-year safety profile of pegaptanib sodium is favorable in patients with exudative AMD. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Eye & Ear Infirm, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. Johns Hopkins Univ, Wilmer Ophthalmol Inst, Baltimore, MD 21218 USA. RP D'Amico, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Eye & Ear Infirm, Dept Ophthalmol,Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM djdamico@meei.harvard.edu RI Larsen, Michael/E-9620-2010 OI Larsen, Michael/0000-0002-5172-5891 NR 22 TC 139 Z9 146 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 2006 VL 113 IS 6 BP 992 EP 1001 DI 10.1016/j.ophtha.2006.02.027 PG 10 WC Ophthalmology SC Ophthalmology GA 050KI UT WOS:000238085900019 ER PT J AU Dang, AC Warren, AP Kim, HT AF Dang, AC Warren, AP Kim, HT TI Beneficial effects of intra-articular caspase inhibition therapy following osteochondral injury SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE cartilage; apoptosis; cell death; programmed cell death; arthritis; caspase inhibition ID APOPTOTIC CHONDROCYTE DEATH; ARTICULAR-CARTILAGE; IN-VIVO; OSTEOARTHRITIC CARTILAGE; CELL-DEATH; REPAIR; DEGRADATION; FRACTURE; DEFECTS; HUMANS AB Objective: Recent studies have demonstrated that articular cartilage injury leads to chondrocyte death through a mechanism termed "apoptosis", or programmed cell death (PCD). Inhibitors of caspases, key enzymatic mediators of apoptosis, have been shown to block chondrocyte PCD. We hypothesized that short-term intra-articular administration of a potent caspase inhibitor would decrease chondrocyte PCD and subsequent cartilage degeneration following experimental osteochondral injury in rabbits. Methods: Adult New Zealand white rabbits were subjected to osteochondral injuries of their femoral condyles. Knees in the treatment group received daily intra-articular injections of the broad-spectrum caspase inhibitor Z-VAD-fmk for 7 days, while the control group received injections of Vehicle alone. Seven days postinjury, one group of rabbits was sacrificed to assess levels of chondrocyte PCD. A second group was sacrificed 42 days postinjury for histological evaluation to measure cartilage degeneration and cartilage repair. Results: Seven days postinjury, there was a 45% reduction in chondrocyte PCD in the caspase inhibitor treated knees as compared to controls (P = 0.01). Forty-two days postinjury, treated knees were found to have 17.9% greater chondrocyte survival (P < 0.01) and 7.6% greater articular cartilage thickness (P = 0.01). Conclusions: Intra-articular administration of the caspase inhibitor Z-VAD-fmk effectively blocks chondrocyte PCD following experimental osteochondral injury in this model. Inhibition of chondrocyte PCD rescues chondrocytes that would otherwise die, limiting subsequent cartilage loss. To our knowledge, this study is the first to demonstrate that short-term inhibition of chondrocyte PCD leads to long-term preservation of cartilage in vivo. (c) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 San Francisco VA Med Ctr, Dept Orthopaed Surg, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. RP Kim, HT (reprint author), San Francisco VA Med Ctr, Dept Orthopaed Surg, 4150 Clement St 112, San Francisco, CA 94121 USA. EM kimh@orthosurg.ucsf.edu NR 26 TC 20 Z9 21 U1 1 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JUN PY 2006 VL 14 IS 6 BP 526 EP 532 DI 10.1016/j.joca.2005.12.010 PG 7 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 055QL UT WOS:000238465300003 PM 16483806 ER PT J AU Metson, R Pletcher, SD AF Metson, R Pletcher, SD TI Endoscopic orbital and optic nerve decompression SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID GRAVES OPHTHALMOPATHY; SHEATH DECOMPRESSION; NEUROPATHY; RADIOTHERAPY; DIPLOPIA; STRUT AB Endoscopic orbital decompression has become the surgical treatment of choice for many patients with orbital manifestations of Graves' disease, including proptosis and optic neuropathy. The unparalleled visualization provided by endoscopic instrumentation allows for a safe and thorough decompression, particularly when operating along the orbital apex and skull base. Although the benefits of and indications for decompression of the orbit are well established, the role of optic nerve decompression remains controversial. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Metson, R (reprint author), 0 Emerson Pl,Suite 2D, Boston, MA 02114 USA. EM ralph_metson@meei.harvard.edu NR 26 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD JUN PY 2006 VL 39 IS 3 BP 551 EP + DI 10.1016/j.otc.2006.01.004 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA 056FR UT WOS:000238507600011 PM 16757231 ER PT J AU Goguen, LA Posner, MR Norris, CM Tishler, RB Wirth, LJ Annino, DJ Gagne, A Sullivan, CA Sarnmartino, DE Haddad, RI AF Goguen, LA Posner, MR Norris, CM Tishler, RB Wirth, LJ Annino, DJ Gagne, A Sullivan, CA Sarnmartino, DE Haddad, RI TI Dysphagia after sequential chemoradiation therapy for advanced head and neck cancer SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; QUALITY-OF-LIFE; RADIATION-THERAPY; SWALLOWING DYSFUNCTION; CHEMOTHERAPY; ASPIRATION; TRIAL; CONCURRENT; CISPLATIN AB OBJECTIVES: Assess impact of sequential chemoradiation therapy (SCRT) for advanced head and neck cancer (HNCA) on swallowing, nutrition, and quality of life. STUDY DESIGN: Prospective cohort study of 59 patients undergoing SCRT for advanced head and neck cancer. Follow-up median was 47.5 months. SETTING: Regional Cancer Center. RESULTS: Median time to gastrostomy tube removal was 21 weeks. Eighteen of 23 patients who underwent modified barium swallow demonstrated aspiration; none developed pneumonia. Six of 7 with pharyngoesophageal stricture underwent successful dilatation. Functional Assessment of Cancer Therapy-Head and Neck Scale questionnaires at median 6 months after treatment revealed "somewhat" satisfaction with swallowing. At the time of analysis, 97% have the gastronomy tube removed and take soft/regular diet. CONCLUSION: Early after treatment dysphagia adversely affected weight, modified barium swallow results, and quality of life. Diligent swallow therapy, and dilation as needed, allowed nearly all patients to have their gastronomy tubes removed and return to a soft/regular diet. SIGNIFICANCE: Dysphagia is significant after SCRT but generally slowly recovers 6 to 12 months after SCRT. C1 Brigham & Womens Hosp, Dept Surg, Div Otolaryngol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Speech & Swallowing, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Goguen, LA (reprint author), Brigham & Womens Hosp, Dept Surg, Div Otolaryngol, 45 Francis St, Boston, MA 02115 USA. EM Igoguen@partners.org NR 22 TC 59 Z9 63 U1 0 U2 7 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 2006 VL 134 IS 6 BP 916 EP 922 DI 10.1016/j.otohns.2006.02.001 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 052KF UT WOS:000238231900005 PM 16730530 ER PT J AU Wang, HB Northrop, C Burgess, B Liberman, MC Merchant, SN AF Wang, HB Northrop, C Burgess, B Liberman, MC Merchant, SN TI Three-dimensional virtual model of the human temporal bone: A stand-alone, downloadable teaching tool SO OTOLOGY & NEUROTOLOGY LA English DT Article DE histologic section; human temporal bone; surface rendering; three-dimensional reconstruction ID 3-D RECONSTRUCTION; 3D RECONSTRUCTION; MICROSCOPY AB Objective: To develop a three-dimensional virtual model of a human temporal bone based on serial histologic sections. Background: The three-dimensional anatomy of the human temporal bone is complex, and learning it is a challenge for students in basic science and in clinical medicine. Methods: Every fifth histologic section from a 14-year-old male was digitized and imported into a general purpose three-dimensional rendering and analysis software package called Amira (version 3.1). The sections were aligned, and anatomic structures of interest were segmented. Results: The three-dimensional model is a surface rendering of these structures of interest, which currently includes the bone and air spaces of the temporal bone; the perilymph and endolymph spaces; the sensory epithelia of the cochlear and vestibular labyrinths; the ossicles and tympanic membrane; the middle car muscles; the carotid artery; and the cochlear, vestibular, and facial nerves. For each structure, the surface transthree-dimensional relations between surface landmarks and underlying structures. The three-dimensional surface model can also be "sliced open" at any section and the appropriate raw histologic image superimposed on the cleavage plane. The image stack can also be resectioned in any arbitrary plane. Conclusion: This model is a powerful teaching tool for learning the complex anatomy of the human temporal bone and for relating the two-dimensional morphology seen in a histologic section to the three-dimensional anatomy. The model can be downloaded from the Eaton-Peabody Laboratory web site, packaged within a cross-platform freeware three-dimensional viewer, which allows full rotation and transparency control. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. RP Wang, HB (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM haobing_wang@meei.harvard.edu FU NIDCD NIH HHS [P30 DC005209, N01-DC-4-0001, P30 DC05209, R01 DC000188] NR 16 TC 32 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUN PY 2006 VL 27 IS 4 BP 452 EP 457 DI 10.1097/00129492-200606000-00004 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 047UA UT WOS:000237903000003 PM 16791035 ER PT J AU Bartling, SH Gupta, R Torkos, A Dullin, C Eckhardt, G Lenarz, T Becker, H Stover, T AF Bartling, SH Gupta, R Torkos, A Dullin, C Eckhardt, G Lenarz, T Becker, H Stover, T TI Flat-panel volume computed tomography for cochlear implant electrode array examination in isolated temporal bone specimens SO OTOLOGY & NEUROTOLOGY LA English DT Article DE computed tomography; cochlear implantation; flat-panel volume computed tomography multislice computed tomography ID CT; SURGERY AB Hypothesis: Flat-panel based volume Computed tomography could improve cochlear implant electrode evaluation in comparison with multislice computed tomography. Background: Flat-panel based Volume computed tomography offers higher spatial resolution and less metal artifacts than multislice computed tomography. Both characteristics could improve the evaluation of challenging but important questions in cochlear implantation assessment, such as an exact imaging of cochlea. osseous spiral lamina, electrode array position, and single electrode contacts. These questions are not currently fully answered by multislice computed tomography. Methods: Four isolated temporal bone specimens were scanned in a current multislice computed tomography scanner and in two experimental flat-panel based volume computed tomography scanners before and after cochlea implantation. To compare flat-panel based volume computed tomography and multislice computed tomography. four features were rated according to the following criteria: 1) 'visibility of the cochlea; 2) visibility of the osscous spiral lamina; 3) discernibility of individual electrode contacts: and 4) the ability to determine the electrode array position relative to scala tympani and scala vestibuli. Layer-by-layer microgrinding pictures were used as the ground truth for verification of imaging findings. Results: Flat-panel based volume computed tomography was superior to multislice computed tomography in all four features rated. The cochlea and facial nerve canal were much better delineated in flat-panel based volume computed tomography. The osseous spiral lamina and single electrode contacts were only visible in flat-panel based volume computed tomography. Assessment of implant position with regard to the cochlear spaces was considerably improved by flat-panel based volume computed tomography. Conclusion: Cochlear implantation assessment could be improved by flat-panel based volume computed tomography and, therefore, would be highly beneficial for cochlea implantation research and for clinical evaluation. However, these first results were shown by scanning isolated temporal bone specimens; scanning whole human skull bases might be more challenging. C1 Hannover Med Sch, Dept Neuroradiol, D-30625 Hannover, Germany. Hannover Med Sch, Dept Otorhinolaryngol, D-30625 Hannover, Germany. Goettingen Univ Hosp, Dept Diagnost Radiol, Gottingen, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Szeged, Clin Otorhinolaryngol & Head & Neck Surg, H-6720 Szeged, Hungary. RP Bartling, SH (reprint author), Hannover Med Sch, Dept Neuroradiol, OE 8210,Carl Neuberg Str 1, D-30625 Hannover, Germany. EM soenkebartling@gmx.de NR 24 TC 25 Z9 25 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUN PY 2006 VL 27 IS 4 BP 491 EP 498 DI 10.1097/00129492-200606000-00010 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 047UA UT WOS:000237903000009 PM 16791040 ER PT J AU Ting, DY AF Ting, DY TI Certain hope SO PATIENT EDUCATION AND COUNSELING LA English DT Editorial Material C1 Harvard Univ, Combined Med Pediat Program, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ting, DY (reprint author), Harvard Univ, Combined Med Pediat Program, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dting@partners.org NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JUN PY 2006 VL 61 IS 3 BP 317 EP 318 DI 10.1016/j.pec.2005.11.012 PG 2 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 058KJ UT WOS:000238663600002 PM 16881138 ER PT J AU Patenaude, AF AF Patenaude, AF TI Assessing adolescents accurately: Evidence of need for the multi-disciplinary pediatric oncology clinic SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Patenaude, AF (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM andrea_patenaude@dfci.harvard.edu NR 2 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 PY 2006 VL 46 IS 7 BP 717 EP 718 DI 10.1002/pbc.20732 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 039KJ UT WOS:000237304100004 ER PT J AU Drobac, PC Mukherjee, JS Joseph, JK Mitnick, C Furin, JJ del Castillo, H Shin, SS Becerra, MC AF Drobac, PC Mukherjee, JS Joseph, JK Mitnick, C Furin, JJ del Castillo, H Shin, SS Becerra, MC TI Community-based therapy for children with multidrug-resistant tuberculosis SO PEDIATRICS LA English DT Article DE tuberculosis; multidrug resistance; international child health ID DRUG-RESISTANT; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; CHILDHOOD TUBERCULOSIS; MDR-TB; PEDIATRIC-PATIENTS; YOUNG-CHILDREN; DOTS-PLUS; EXPERIENCE; PERU AB OBJECTIVES. The goals were to describe the management of multidrug-resistant tuberculosis among children, to examine the tolerability of second-line antituberculosis agents among children, and to report the outcomes of children treated for multidrug-resistant tuberculosis in poor urban communities in Lima, Peru, a city with high tuberculosis prevalence. METHODS. A retrospective analysis of data for 38 children < 15 years of age with multidrug-resistant tuberculosis, either documented with drug sensitivity testing of the child's tuberculosis isolate or suspected on the basis of the presence of clinical symptoms for a child with a household contact with documented multidrug-resistant tuberculosis, was performed. All 38 children initiated a supervised individualized treatment regimen for multidrug-resistant tuberculosis between July 1999 and July 2003. Each child received 18 to 24 months of therapy with >= 5 first- or second-line drugs to which their Mycobacterium tuberculosis strain was presumed to be sensitive. RESULTS. Forty-five percent of the children had malnutrition or anemia at the time of diagnosis, 29% had severe radiographic findings (defined as bilateral or cavitary disease), and 13% had extrapulmonary disease. Forty-five percent of the children were hospitalized initially because of the severity of illness. Adverse events were observed for 42% of the children, but no events required suspension of therapy for >= 5 days. Ninety-five percent of the children (36 of 38 children) achieved cures or probable cures, 1 child (2.5%) died, and 1 child (2.5%) defaulted from therapy. CONCLUSIONS. Multidrug-resistant tuberculosis disease among children can be treated successfully in resource-poor settings. Treatment is well tolerated by children, and severe adverse events with second-line agents are rare. C1 Brigham & Womens Hosp, Div Social Med & Hlth Inequalities, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02120 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Socios Salud Sucursal Peru, Lima, Peru. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Inst Salud Nino, Lima, Peru. RP Drobac, PC (reprint author), Brigham & Womens Hosp, Div Social Med & Hlth Inequalities, 1 Brigham Circle,1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM pdrobac@partners.org NR 56 TC 49 Z9 49 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2006 VL 117 IS 6 BP 2022 EP 2029 DI 10.1542/peds.2005-2235 PG 8 WC Pediatrics SC Pediatrics GA 048XE UT WOS:000237979000020 PM 16740844 ER PT J AU Ly, NP Gold, DR Weiss, ST Celedon, JC AF Ly, NP Gold, DR Weiss, ST Celedon, JC TI Recurrent wheeze in early childhood and asthma among children at risk for atopy SO PEDIATRICS LA English DT Article DE wheeze; asthma; atopy; parental asthma; early childhood ID DAY-CARE ATTENDANCE; RESPIRATORY-TRACT; 1ST YEAR; LIFE; AGE; ILLNESSES; HISTORY; COHORT; SEX AB OBJECTIVES. Little is known about the natural history of wheezing disorders among children at risk for atopy. We examined the relation between early wheeze and asthma at 7 years of age among children with parental history of asthma or allergies followed from birth. METHODS. Information on wheeze was collected bimonthly from birth to age 24 months and every 6 months thereafter. Recurrent early wheeze was defined as >= 2 reports of wheezing in the first 3 years of life. Frequent early wheeze was defined as >= 2 reports of wheezing per year in the first 3 years of life. At 7 years of age, asthma was defined as physician-diagnosed asthma and wheezing in the previous year. RESULTS. Of the 440 participating children, 223 (50.7%) had >= 1 report of wheeze before 3 years old, 111 (26.0%) had recurrent early wheeze, and 12 (2.7%) had frequent early wheeze. Whereas only 31 (13.9%) of 223 children with >= 1 report of wheeze developed asthma at 7 years of age, 24 (21.6%) of 111 children with recurrent early wheeze developed asthma at 7 years of age. Among the 12 children with frequent early wheeze, 6 (50%) had asthma at 7 years of age. After adjustment for other covariates, recurrent early wheeze in children at risk for atopy was associated with a fourfold increase in the odds of asthma at 7 years of age, and frequent early wheeze was associated with an similar to 12-fold increase in the odds of asthma at 7 years of age. Most (94%) of the children without frequent early wheeze did not develop asthma at 7 years of age. CONCLUSIONS. The absence of recurrent early wheeze indicates a very low risk of asthma at school age among children with parental history of asthma or allergies. Early identification of children who will develop asthma at school age is difficult, even in children at risk for atopy. However, children with parental history of asthma or allergies who have frequent early wheeze, in particular, are at greatly increased risk of asthma and merit close clinical follow-up. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Div Pediat Pulm Med, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02215 USA. RP Celedon, JC (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave,4th Floor, Boston, MA 02115 USA. EM rejcc@channing.harvard.edu FU NHLBI NIH HHS [HL07427]; NIAID NIH HHS [AI 45007, AI45007, AI35786]; PHS HHS [EHS35786, EHS45007] NR 21 TC 31 Z9 31 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2006 VL 117 IS 6 BP E1132 EP E1138 DI 10.1542/peds.2005-2271 PG 7 WC Pediatrics SC Pediatrics GA 048XE UT WOS:000237979000092 PM 16740815 ER PT J AU Martinez, V Wang, L Tache, Y AF Martinez, V Wang, L Tache, Y TI Peripheral adrenomedullin inhibits gastric emptying through CGRP(8-37)-sensitive receptors and prostaglandins pathways in rats SO PEPTIDES LA English DT Article DE adrenomedullin; beta-adrenergic receptors; gastric emptying; CGRP; CGRP(8-37); prostaglandins ID GENE-RELATED PEPTIDE; PROADRENOMEDULLIN N-TERMINAL-20 PEPTIDE; NERVOUS-SYSTEM ACTION; GASTROINTESTINAL TRANSIT; ANESTHETIZED RATS; VASCULAR ACTIONS; CALCITONIN; CGRP; CAPSAICIN; AMYLIN AB The effects of intravenous (iv) adrenomedullin (AM) on gastric emptying were investigated in conscious rats. AM induced a maximal 50% inhibition of gastric emptying at a dose of 1.2 nmol/kg. AM was about two-fold less potent than a-calcitonin gene-related peptide (alpha-CGRP), which induced a similar 50% maximal inhibition of gastric emptying at 0.6 nmol/kg. Delayed gastric emptying induced by i.v. AM and alpha-CGRP was prevented by peripheral injection of the selective CGRP(1) antagonist, CGRP(8-37), and by pretreatment with indomethacin, while not altered by blockade of the sympathetic nervous system with propranolol. These data indicate that peripheral AM inhibits gastric emptying through the interaction with CGRP(8-37)-sensitive receptors, likely CGRP(1) receptors, and the recruitment of prostazglandin-dependent mechanisms. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, CURE, DDRC, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis,Ctr Neurovisceral Sci & Womens Hlt, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90007 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, CURE, DDRC, 11301 Wilshire Blvd,Bldg 115,Room 117, Los Angeles, CA 90073 USA. EM vicente.martinez@astrazeneca.com; ytache@mednet.ucla.edu RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [R01 DK-33061, P30 DK-41301] NR 44 TC 4 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUN PY 2006 VL 27 IS 6 BP 1376 EP 1382 DI 10.1016/j.peptides.2005.11.003 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 055MU UT WOS:000238455600027 PM 16337713 ER PT J AU Pekary, AE Sattin, A Stevens, SA AF Pekary, AE Sattin, A Stevens, SA TI Rapid modulation of TRH-like peptides in rat brain by thyroid hormones SO PEPTIDES LA English DT Article DE TRH; TRH-like peptides; thyroid hormones; depression; limbic system ID SYNAPTOSOMAL NOREPINEPHRINE UPTAKE; IMMATURE SECRETORY GRANULE; MESSENGER-RIBONUCLEIC-ACID; NONGENOMIC ACTIONS; STEROID-HORMONES; POTENT INHIBITOR; THYROXINE; DEIODINASE; THYROTROPIN; DESMETHYLIMIPRAMINE AB Recent identification of membrane receptors for T-4, T-3, 3,5-T-2, and 3-iodothyronamine that mediate rapid physiologic effects of thyroid hormones suggested that such receptors may supplement the regulation of TRH and TRH-like peptides by nuclear T3 receptors. For this reason 200 g male Sprague-Dawley rats received daily i.p. injections of PTU or T4. Levels of TRH and TRH-like peptides were measured 0, 2 h or 1, 2, 3, or 4 days later. Rapid increases or decreases in TRH and TRH-like peptide levels were observed in response to PTU and T4 treatments in various brain regions involved in mood regulation. Significant effects were measured within 2 h of T4 injection. Nuclear T3 receptor-mediated changes in gene expression altering translation, post-translational processing and constitutive release of peptides require more than 2 h. We conclude that non-genomic mechanisms may contribute to the psychiatric effects of thyroid disease and thyroid hormone adjuvant treatment for major depression. Published by Elsevier Inc. C1 Univ Calif Los Angeles, Res Serv, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Pekary, AE (reprint author), Univ Calif Los Angeles, Res Serv, VA Greater Los Angeles Healthcare Syst, Bldg 114,Rm 229,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Eugene.Pekary@med.va.gov NR 53 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUN PY 2006 VL 27 IS 6 BP 1577 EP 1588 DI 10.1016/j.peptides.2005.10.015 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 055MU UT WOS:000238455600054 PM 16310891 ER PT J AU Dezso, Z Almaas, E Lukacs, A Racz, B Szakadat, I Barabasi, AL AF Dezso, Z. Almaas, E. Lukacs, A. Racz, B. Szakadat, I. Barabasi, A. -L. TI Dynamics of information access on the web SO PHYSICAL REVIEW E LA English DT Article ID WORLD-WIDE-WEB; COMPLEX NETWORKS; DIFFUSION; ORGANIZATION; INTERNET AB While current studies on complex networks focus on systems that change relatively slowly in time, the structure of the most visited regions of the web is altered at the time scale from hours to days. Here we investigate the dynamics of visitation of a major news portal, representing the prototype for such a rapidly evolving network. The nodes of the network can be classified into stable nodes, which form the time-independent skeleton of the portal, and news documents. The visitations of the two node classes are markedly different, the skeleton acquiring visits at a constant rate, while a news document's visitation peaks after a few hours. We find that the visitation pattern of a news document decays as a power law, in contrast with the exponential prediction provided by simple models of site visitation. This is rooted in the inhomogeneous nature of the browsing pattern characterizing individual users: the time interval between consecutive visits by the same user to the site follows a power-law distribution, in contrast to the exponential expected for Poisson processes. We show that the exponent characterizing the individual user's browsing patterns determines the power-law decay in a document's visitation. Finally, our results document the fleeting quality of news and events: while fifteen minutes of fame is still an exaggeration in the online media, we find that access to most news items significantly decays after 36 hours of posting. C1 Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. Lawrence Livermore Natl Lab, Biosci Directorate, Microbial Syst Div, Livermore, CA 94551 USA. Hungarian Acad Sci, MTA, SZTAKI, Comp & Automat Res Inst, Budapest, Hungary. Axelero Internet Provider Inc, H-1364 Budapest, Hungary. Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Dezso, Z (reprint author), Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. EM alb@nd.edu RI Szakadat, Istvan/H-3517-2012; OI Szakadat, Istvan/0000-0002-1960-191X; Almaas, Eivind/0000-0002-9125-326X NR 56 TC 117 Z9 130 U1 1 U2 15 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 2006 VL 73 IS 6 AR 066132 DI 10.1103/PhysRevE.73.066132 PN 2 PG 6 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 058WB UT WOS:000238694200050 PM 16906939 ER PT J AU Goh, KI Eom, YH Jeong, H Kahng, B Kim, D AF Goh, K. -I. Eom, Y. -H. Jeong, H. Kahng, B. Kim, D. TI Structure and evolution of online social relationships: Heterogeneity in unrestricted discussions SO PHYSICAL REVIEW E LA English DT Article ID NETWORKS; COMMUNITY; TOPOLOGY; SEARCH AB With the advancement in the information age, people are using electronic media more frequently for communications, and social relationships are also increasingly resorting to online channels. While extensive studies on traditional social networks have been carried out, little has been done on online social networks. Here we analyze the structure and evolution of online social relationships by examining the temporal records of a bulletin board system (BBS) in a university. The BBS dataset comprises of 1908 boards, in which a total of 7446 students participate. An edge is assigned to each dialogue between two students, and it is defined as the appearance of the name of a student in the from- and to-field in each message. This yields a weighted network between the communicating students with an unambiguous group association of individuals. In contrast to a typical community network, where intracommunities (intercommunities) are strongly (weakly) tied, the BBS network contains hub members who participate in many boards simultaneously but are strongly tied, that is, they have a large degree and betweenness centrality and provide communication channels between communities. On the other hand, intracommunities are rather homogeneously and weakly connected. Such a structure, which has never been empirically characterized in the past, might provide a new perspective on the social opinion formation in this digital era. C1 Seoul Natl Univ, Sch Phys, Seoul 151747, South Korea. Seoul Natl Univ, Ctr Theoret Phys, Seoul 151747, South Korea. Korea Adv Inst Sci & Technol, Dept Phys, Taejon 305701, South Korea. Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA. RP Goh, KI (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RI Jeong, Hawoong/C-1587-2011; Jeong, Hawoong/A-2469-2009 OI Jeong, Hawoong/0000-0002-2491-8620 NR 30 TC 27 Z9 31 U1 0 U2 9 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2470-0045 EI 2470-0053 J9 PHYS REV E JI Phys. Rev. E PD JUN PY 2006 VL 73 IS 6 AR 066123 DI 10.1103/PhysRevE.73.066123 PN 2 PG 8 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 058WB UT WOS:000238694200041 PM 16906930 ER PT J AU Barth, WH McCurnin, DC Carey, KD Hankins, GDV AF Barth, WH McCurnin, DC Carey, KD Hankins, GDV TI Contrast sonography, video densitometry and intervillous blood flow: A pilot project SO PLACENTA LA English DT Article DE ultrasound contrast; intervillous blood flow; uteroplacental blood flow; contrast sonography ID INTRAUTERINE GROWTH-RETARDATION; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; INTRAVENOUS XE-133 METHOD; EARLY-PREGNANCY; TROPHOBLAST INVASION; MYOCARDIAL PERFUSION; BASIC PRINCIPLES; MACACA-MULATTA; RHESUS-MONKEY; AGENTS AB Purpose: To examine the feasibility of constructing time-intensity (TI) curves from the intervillous space with an intravascular ultrasound contrast agent and computer assisted video densitometry. Study design: We sedated nine pregnant baboons, optimized the grey scale and color Doppler images of their placentas, and then fixed the transducers in place. For each injection of contrast, we recorded images on videotape without changing the ultrasound image processing functions. Video images were captured using a Macintosh personal computer equipped with a video-capture board using image analysis software (Image 1.4, W Rasband, NIH). For each injection, we sampled digitized images of a fixed region of interest at regular intervals. After computing the mean video density of each image, we used the sampling frequency to construct TI curves depicting any change over time as the contrast agents washed into and out of the intervillous space. Results: Three of four agents tested produced changes in the video density of the placenta. TI curves were established using both grey scale and color Doppler signal augmentation. As expected, intra-arterial agents produced rapid accumulation and decay. Intravenous agents produced more protracted effects secondary to bolus dilution and transit through the right heart and pulmonary vascular bed. Conclusion: TI curves may be generated from the intervillous space with the use of a transpulmonary ultrasound contrast agent and video densitometry. If validated by further study, this may allow investigators to apply ultrasound and indicator-dilution theory to intervillous blood flow. C1 Massachusetts Gen Hosp, Vincent Mem Hosp, Womens Care Div, Boston, MA 02114 USA. SW Fdn Biomed Res, Dept Comparat Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78285 USA. Univ Texas, Med Branch, Dept Obstet & Gynecol, Galveston, TX 77550 USA. RP Barth, WH (reprint author), Massachusetts Gen Hosp, Vincent Mem Hosp, Womens Care Div, 55 Fruit St,Founders 401, Boston, MA 02114 USA. EM wbarthjr@partners.org NR 43 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD JUN-JUL PY 2006 VL 27 IS 6-7 BP 719 EP 726 DI 10.1016/j.placenta.2005.07.007 PG 8 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 043NI UT WOS:000237607500023 PM 16157372 ER PT J AU Lipsky, BA Berendt, AR Deery, HG Embil, JM Joseph, WS Karchmer, AW LeFrock, JL Lew, DP Mader, JT Norden, C Tan, JS AF Lipsky, Benjamin A. Berendt, Anthony R. Deery, H. Gunner Embil, John M. Joseph, Warren S. Karchmer, Adolf W. LeFrock, Jack L. Lew, Daniel P. Mader, Jon T. Norden, Carl Tan, James S. TI Diagnosis and treatment of diabetic foot infections SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Review ID COLONY-STIMULATING FACTOR; SOFT-TISSUE INFECTIONS; RESISTANT STAPHYLOCOCCUS-AUREUS; PERIPHERAL VASCULAR-DISEASE; ARTERIAL OCCLUSIVE DISEASE; LOWER-EXTREMITY INFECTIONS; CUTANEOUS OXYGEN-TENSION; OPEN-LABEL TRIAL; TERM-FOLLOW-UP; HYPERBARIC-OXYGEN AB Executive Summary: 1. Foot infections in patients with diabetes cause substantial morbidity and frequent visits to health care professionals and may lead to amputation of a lower extremity. 2. Diabetic foot infections require attention to local (foot) and systemic (metabolic) issues and coordinated management, preferably by a multidisciplinary foot-care team (A-II) (Table 1). The team managing these infections should include, or have ready access to, an infectious diseases specialist or a medical microbiologist (B-II). 3. The major predisposing factor to these infections is foot ulceration, which is usually related to peripheral neuropathy. Peripheral vascular disease and various immunological disturbances play a secondary role. 4. Aerobic Gram-positive cocci (especially Staphylococcus aureus) are the predominant pathogens in diabetic foot infections. Patients who have chronic wounds or who have recently received antibiotic therapy may also be infected with Gram-negative rods, and those with foot ischemia or gangrene may have obligate anaerobic pathogens. 5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signs and symptoms of inflammation. Laboratory (including microbiological) investigations arc of limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6. Send appropriately obtained specimens for culture before starting empirical antibiotic therapy in all cases of infection, except perhaps those that are mild and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging studies may help diagnose or better define deep, soft-tissue purulent collections and are usually needed to detect pathological findings in bone. Plain radiography may be adequate in many cases, but MRI (in preference to isotope scanning) is more sensitive and specific, especially for detection of soft-tissue lesions (A-I). 8. Infections should be categorized by their severity on the basis of readily assessable clinical and laboratory features (B-II). Most important among these are the specific tissues involved, the adequacy of arterial per-fusion, and the presence of systemic toxicity or metabolic instability. Categorization helps determine the degree of risk to the patient and the limb and, thus, the urgency and venue of management. 9. Available evidence does not support treating clinically uninfected ulcers with antibiotic therapy (D-III). Antibiotic therapy is necessary for virtually all infected wounds, but it is often insufficient without appropriate wound care. 10. Select an empirical antibiotic regimen on the basis of the severity of the infection and the likely etiologic agent(s) (B-II). Therapy aimed solely at aerobic Gram-positive cocci may be sufficient for mild-to-moderate infections in patients who have not recently received antibiotic therapy (A-II). Broad-spectrum empirical therapy is not routinely required but is indicated for severe infections, pending culture results and antibiotic susceptibility data (B-III). Take into consideration any recent antibiotic therapy and local antibiotic susceptibility data, especially the prevalence of methicillin-resistant S. aureus (MRSA) or other resistant organisms. Definitive therapy should be based on both the culture results and susceptibility data and the clinical response to the empirical regimen (C-III). 11. There is only limited evidence with which to make informed choices among the various topical, oral, and parenteral antibiotic agents. Vitually all severe and some moderate infections require parenteral therapy, at least initially (C-III). Highly bioavailable oral antibiotics can be used in most mild and in many moderate infections, including some cases of osteomyelitis (A-II). Topical therapy may be used for some mild superficial infections (B-I). 12. Continue antibiotic therapy until there is evidence that the infection has resolved but not necessarily until a wound has healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 12 weeks usually suffices, but some require an additional 12 weeks; for moderate and severe infections, usually 24 weeks is sufficient, depending on the structures involved, the adequacy of debridement, the type of soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis, generally at least 46 weeks is required, but a shorter duration is sufficient if the entire infected bone is removed, and probably a longer duration is needed if infected bone remains (B-II). 13. If an infection in a clinically stable patient fails to respond to I antibiotic courses, consider discontinuing all antimicrobials and, after a few days, obtaining optimal culture specimens (C-III). 14. Seek surgical consultation and, when needed, intervention for infections accompanied by a deep abscess, extensive bone or joint involvement, crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II). Evaluating the limb's arterial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the field should be recruited by the foot-care team, if possible. 15. Providing optimal wound care, in addition to appropriate antibiotic treatment of the infection, is crucial for healing (A-I). This includes proper wound cleansing, debridement of any callus and necrotic tissue, and, especially, off-loading of pressure. There is insufficient evidence to recommend use of a specific wound dressing or any type of wound healing agents or products for infected foot wounds. 16. Patients with infected wounds require early and careful follow-up observation to ensure that the selected medical and surgical treatment regimens have been appropriate and effective (B-III). 17. Studies have not adequately defined the role of most adjunctive therapies for diabetic foot infections, but systematic reviews suggest that granulocyte colony stimulating factors and systemic hyperbaric oxygen therapy may help prevent amputations (B-I). These treatments may be useful for severe infections or for those that have not adequately responded to therapy, despite correcting for all amenable local and systemic adverse factors. 18. Spread of infection to bone (osteitis or osteomyelitis) may be difficult to distinguish from noninfectious osteoarthropathy. Clinical examination and imaging tests may suffice, but bone biopsy is valuable for establishing the diagnosis of osteomyelitis, for defining the pathogenic organism(s), and for determining the antibiotic susceptibilities of such organisms (B-II). 19. Although this field has matured, further research is much needed. The committee especially recommends that adequately powered prospective studies be undertaken to elucidate and validate systems for classifying infection, diagnosing osteomyelitis, defining optimal antibiotic regimens in various situations, and clarifying the role of surgery in treating osteomyelitis (A-III). C1 Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. Nuffield Orthopaed Ctr, Bone Infect Unit, Oxford, England. Univ Manitoba, Dept Med, Infect Dis Sect, Winnipeg, MB R3T 2N2, Canada. Harvard Univ, Sch Med, Dept Med, Div Infect Dis, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Hosp Geneva, Dept Med, Infect Dis Serv, Geneva, Switzerland. Univ Texas, Med Branch, Inst Marine Biomed, Dept Internal Med, Galveston, TX USA. Univ Texas, Med Branch, Dept Orthopaed & Rehabil, Galveston, TX USA. New Jersey Med Sch & Dent, Dept Med, Newark, NJ USA. Univ Med & Dent New Jersey, Cooper Hosp, Camden, NJ 08103 USA. Northeastern Ohio Univ Coll Med & Pharm, Summa Hlth Syst, Dept Internal Med, Rootstown, OH USA. RP Lipsky, BA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Med Serv, S-111-GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. EM Benjamin.Lipsky@med.va.gov RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 296 TC 75 Z9 83 U1 2 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2006 VL 117 IS 7 SU S BP 212S EP 238S DI 10.1097/01.prs.0000222737.09322.77 PG 27 WC Surgery SC Surgery GA 056UA UT WOS:000238549400022 PM 16799390 ER PT J AU Russell, JA Conforti, ML Connor, NP Hartig, GK AF Russell, JA Conforti, ML Connor, NP Hartig, GK TI Cutaneous tissue flap viability following partial venous obstruction SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LEECH HIRUDO-MEDICINALIS; SKIN FLAPS; MECHANICAL DEVICE; ISLAND FLAPS; ISCHEMIA; CONGESTION; ARTERIAL; FLOW; OXYGENATION; OCCLUSION AB Background: Venous outflow obstruction is the most common cause of tissue failure after microvascular reconstructive surgery. If it is not recognized early, there is an increased risk of tissue damage and loss. Currently, however, there are no adequate models for the study of this clinical problem. The purpose of this study was to develop a partial congestion model for the study of skin flap physiology in response to varying levels of occluded venous outflow. Methods: Nine mixed-breed pigs were equally divided into three experimental groups (0 percent, 20 percent, and 50 percent venous outflow) to determine the effects of varying venous outflow on cutaneous flap color, oxygen tension, and edema. A cutaneous pedicle flap model and a partial congestion system were used to observe changes in variable venous obstruction. Results: Only 0 percent venous outflow resulted in progressive color change across time. In addition, 0 percent venous outflow demonstrated significantly different oxygen tension levels relative to the other groups. Twenty percent venous outflow resulted in significant edema formation relative to the other groups. The 50 percent group showed an increase in oxygen tension from, the second hour of venous obstruction to the end of the experiment. Conclusions: Tissue flap color is the clinical standard on which flap health is measured. After 8 hours, only complete venous occlusion resulted in significant color change. However, physiological changes that could affect tissue flap health were noted with only partial venous occlusion, including the development of edema formation. Accordingly, subtle color change could indicate partial venous congestion and may warrant intervention by the surgeon. C1 Univ Wisconsin, Ctr Clin Sci, Dept Surg, Div Otolaryngol Head & Neck Surg, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Dept Commun Disorders, Madison, WI 53792 USA. RP Connor, NP (reprint author), Univ Wisconsin, Ctr Clin Sci, Dept Surg, Div Otolaryngol Head & Neck Surg, Room K4-711,600 Highland Ave, Madison, WI 53792 USA. EM connor@surgery.wisc.edu NR 22 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2006 VL 117 IS 7 BP 2259 EP 2266 DI 10.1097/01.prs.0000225472.57337.2e PG 8 WC Surgery SC Surgery GA 055DZ UT WOS:000238431500023 PM 16772926 ER PT J AU Donelan, MB Garcia, JA AF Donelan, MB Garcia, JA TI Nailfold reconstruction for correction of burn fingernail deformity SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ONE-STAGE RECONSTRUCTION; PERIONYCHIUM; CONTRACTURE; RETRACTION; PHYSIOLOGY; ANATOMY AB Background: Fingernail deformities frequently occur after burn injury to the hand. In many cases, the deformity is not the result of injury to the nail bed or germinal matrix but is instead secondary to contracture of soft tissues proximal to the eponychium. The roof of the nailfold peels away from the nail, causing abnormal nail growth and appearance. Alterations in appearance can range from subtle changes in contour and location of the eponychium to complete loss of germinal matrix and absence of nail growth. The majority of patients fall into a midrange category that includes multiple symptoms. The important concept, however, is that in many cases the complex structure of the nailfold is not destroyed by the injury but is only displaced by the proximal contracture. Methods: This deformity is readily treatable with a simple, reliable procedure that releases the proximal contracture with a distally based bipedicled flap and resurfacing with a skin graft. Results: Contracture release allows the displaced and everted roof of the nailfold to slide distally without tension and restores normal nailfold anatomy. The contribution of the dorsal nail matrix to nail growth is restored, improving fingernail appearance and function. Over the past 20 years, this technique has been used in over 100 digits with burn fingernail deformities. There have been no instances of flap loss. Conclusions: This is a simple, straightforward procedure, with few complications, that relieves many symptoms associated with burn fingernail deformity. Thousands of burned digits would benefit from this procedure. C1 Harvard Univ, Sch Med, Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Donelan, MB (reprint author), Harvard Univ, Sch Med, Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. EM mdonelan@partners.org NR 13 TC 2 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2006 VL 117 IS 7 BP 2303 EP 2308 DI 10.1097/01.prs.0000218709.03848.a5 PG 6 WC Surgery SC Surgery GA 055DZ UT WOS:000238431500030 PM 16772933 ER PT J AU Park, ER Puleo, E Butterfield, RM Zorn, M Mertens, AC Gritz, ER Lie, FP Emmons, KM AF Park, ER Puleo, E Butterfield, RM Zorn, M Mertens, AC Gritz, ER Lie, FP Emmons, KM TI A process evaluation of a telephone-based peer-delivered smoking cessation intervention for adult survivors of childhood cancer: The partnership for health study SO PREVENTIVE MEDICINE LA English DT Article DE smoking cessation; childhood cancer survivors; telephone counseling; motivational intervention ID LONG-TERM SURVIVORS; SELF-HELP MATERIALS; WOMEN STOP SMOKING; PROMOTION PROGRAMS; NICOTINE PATCHES; BEHAVIORS; SUPPORT; SMOKERS; COHORT; PREDICTORS AB Objective. We report on the process evaluation of an efficacious national smoking cessation intervention for adult survivors of childhood cancer. We examine associations between intervention implementation characteristics and study outcomes, as well as participant characteristics related to level of involvement in the intervention. Methods. The study was conducted at the Dana-Farber Cancer Institute in Boston, Massachusetts, from 1999-2001. Participants (n = 398) were randomly assigned to receive a proactive telephone-based peer counseling intervention. They received up to 6 counseling calls, individually tailored and survivor-targeted materials, and nicotine replacement therapy (NRT) patches if they were prepared to quit smoking. Results. Forty-two percent of survivors participated in the maximum number of calls (5-6), and 29% of participants requested and received NRT. Total counseling time was an average of 51 min. Quit status at follow-up was related to intervention dose, and participants who received NRT were significantly more likely to make a 24-h quit attempt. Demographic variables (females, White), higher daily smoking rate, poorer perceived health and moderate perceived risk of smoking were significantly related to greater intervention involvement. Conclusions. A brief peer-delivered, telephone counseling intervention is an effective way to intervene with adult survivors of childhood cancer who are smoking. Findings from the process evaluation data (call length and number, frequency, and spacing) will inform future telephone counseling cessation programs. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Amherst, MA 01003 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Park, ER (reprint author), Massachusetts Gen Hosp, 50 Stanford St,9th Floor, Boston, MA 02114 USA. EM epark@partners.org FU NCI NIH HHS [U24-CA55727, R01-CA77780] NR 48 TC 22 Z9 22 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUN PY 2006 VL 42 IS 6 BP 435 EP 442 DI 10.1016/j.ypmed.2006.03.004 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 059RV UT WOS:000238750800008 PM 16626797 ER PT J AU Robertson, RH Burkhardt, JH Powell, MP Eloubeidi, MA Pisu, M Weissman, NW AF Robertson, RH Burkhardt, JH Powell, MP Eloubeidi, MA Pisu, M Weissman, NW TI Trends in colon cancer screening procedures in the US Medicare and Tricare populations: 1999-2001 SO PREVENTIVE MEDICINE LA English DT Article DE colorectal cancer; Medicare; Tricare; colonoscopy; flexible sigmoidoscopy; double contrast barium enema ID COLORECTAL-CANCER AB Background. This study examined trends in the numbers of double contrast barium enemas, flexible sigmoidoscopies, and colonoscopies and trends in the choices of colorectal cancer screening service providers. Methods. Descriptive statistics were used to examine Medicare and Tricare data for the years 1999 to 2001. Results. The total volume of procedures increased 5% and 14%, respectively, in Tricare and Medicare. Tricare and Medicare, respectively, saw 32% and 33% reductions in barium enemas and 28% and 41% reductions in flexible sigmoidoscopies. Colonoscopies increased by 45% and 34% in Tricare and Medicare, respectively. Gastroenterologists provided the majority of colonoscopies for both groups each year. Conclusions. The volume of colonoscopies increased from 1999 to 2001 for both groups while the volumes of barium enemas and flexible sigmoidoscopies decreased. Gastroenterologists appear to be the preferred providers of colonoscopies. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Alabama, Sch Hlth Related Profess, Dept Hlth Serv Adm, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Prevent Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. RP Robertson, RH (reprint author), Univ Alabama, Sch Hlth Related Profess, Dept Hlth Serv Adm, Webb 603,1530 3rd Ave S, Birmingham, AL 35294 USA. EM randal78@uab.edu NR 4 TC 28 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUN PY 2006 VL 42 IS 6 BP 460 EP 462 DI 10.1016/j.ypmed.2006.01.014 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 059RV UT WOS:000238750800012 PM 16563479 ER PT J AU Wang, JH Weng, JS Cai, Y Penland, R Liu, MY Ittmann, M AF Wang, JH Weng, JS Cai, Y Penland, R Liu, MY Ittmann, M TI The prostate-specific G-protein coupled receptors PSGR and PSGR2 are prostate cancer biomarkers that are complementary to alpha-methylacyl-CoA racemase SO PROSTATE LA English DT Article DE marker expression; quantitative RT-PCR; in situ hybridization; prostate-specific G-protein coupled receptors; PSGR; PSGR2 ID NEEDLE-BIOPSY SPECIMENS; COENZYME-A RACEMASE; BASAL-CELL MARKERS; RADICAL PROSTATECTOMY; NEPHROGENIC ADENOMA; DIAGNOSTIC UTILITY; EXPRESSION; P504S; FOCI; CARCINOMA AB BACKGROUND. Immunohistochemistry (IHC) to detect alpha-methylacyl-CoA racemase (AMACR) expression can be useful in the diagnosis of small foci of prostate cancer on needle biopsy specimens, although it still has limitations in terms of both sensitivity and specificity. We have previously described the increased expression of two prostate-specific G-protein coupled receptors (PSGR and PSGR2) in human prostate cancer. To examine their potential usefulness as cancer biomarkers, we have evaluated their expression relative to AMACR in prostate cancer tissues. METHODS. Expression of PSGR, PSGR2, and AMACR were examined by quantitative reverse-transcriptase PCR in mRNAs from benign prostate and prostate cancer tissues. Expression of PSGR2 and AMACR was also examined by in situ hybridization using a prostate cancer tissue microarray. RESULTS. By in situ hybridization, 24 of 40 prostate cancer cases showed concordant expression of PSGR2 and AMACR. However, in 16 cases there was significant discordance between expression levels of these two markers. By quantitative RT-PCR all three markers were substantially increased in cancer, with AMACR the most overexpressed (30-fold), followed by PSGR2 (13-fold) and PSGR (10-fold). AMACR was the best single marker of prostate cancer but in 7 of the 59 total cases the expression of AMACR was not significantly elevated while PSGR and/or PSGR2 were substantially elevated. CONCLUSION. All three biomarkers are increased in prostate cancer but their expression is not completely concordant. There is a subset of cases in which analysis of expression of PSGR and/or PSGR2, in addition to AMACR, would be diagnostically useful. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. Texas A&M Univ, Ctr Canc Biol & Nutr, Inst Biosci & Technol, Syst Hlth Sci Ctr, Houston, TX USA. RP Ittmann, M (reprint author), VAMC, Res Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mittmann@bcm.tmc.edu FU NCI NIH HHS [1R21CA104318, P50CA058204] NR 33 TC 31 Z9 33 U1 0 U2 3 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 JUN 1 PY 2006 VL 66 IS 8 BP 847 EP 857 DI 10.1002/pros.20389 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 042RC UT WOS:000237545600007 PM 16491480 ER PT J AU Mao, JR AF Mao, JR TI Opioid tolerance, dependence, and opioid-induced hyperalgesia SO PSYCHIATRIC ANNALS LA English DT Article ID MORPHINE-TOLERANCE; CHRONIC PAIN; THERAPY; RECEPTORS; NMDA C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Pain Ctr, WACC 324,Ctr Translat Pain Res, Boston, MA 02114 USA. RP Mao, JR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Pain Ctr, WACC 324,Ctr Translat Pain Res, Boston, MA 02114 USA. EM jmao@partners.org NR 15 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUN PY 2006 VL 36 IS 6 BP 399 EP 402 PG 4 WC Psychiatry SC Psychiatry GA 052MU UT WOS:000238238600005 ER PT J AU Geller, DA AF Geller, DA TI Obsessive-compulsive and spectrum disorders in children and adolescents SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; 7-YEAR FOLLOW-UP; TOURETTES-SYNDROME; FLUOXETINE TREATMENT; BIPOLAR DISORDER; COMORBID ANXIETY; NAIVE CHILDREN; DOUBLE-BLIND; FAMILY; SYMPTOMS AB Obsessive-compulsive disorder (OCD) affecting children and adolescents is prevalent, and OCD has a childhood onset in about one third to one half of affected adults. Unlike adults, affected children are more often male. Mood and anxiety disorders are common in pediatric OCD; pediatric OCD also has a distinct association with disruptive behavior disorders, tic, and other specific and pervasive developmental disorders. Childhood-onset of OCD seems to be associated with a markedly increased risk for familial transmission of OCD, tic disorders, and ADHD. Both scientifically and clinically, the recognition of developmentally specific OCD phenotypes may be valuable. C1 Massachusetts Gen Hosp, Pediat Obsess Compuls Program, Div Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Geller, DA (reprint author), Massachusetts Gen Hosp, Pediat Obsess Compuls Program, Div Pediat Psychopharmacol, YAW 6A,Fruit St, Boston, MA 02114 USA. EM dan@gellers.org NR 81 TC 95 Z9 100 U1 5 U2 28 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 2006 VL 29 IS 2 BP 353 EP + DI 10.1016/j.psc.2006.02.012 PG 19 WC Psychiatry SC Psychiatry GA 047SL UT WOS:000237898900003 PM 16650713 ER PT J AU Rief, W Buhlmann, U Wilhelm, S Borkenhagen, A Brahler, E AF Rief, W Buhlmann, U Wilhelm, S Borkenhagen, A Brahler, E TI The prevalence of body dysmorphic disorder: a population-based survey SO PSYCHOLOGICAL MEDICINE LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; MAJOR DEPRESSION; SOMATOFORM DISORDERS; CLINICAL-FEATURES; IMAGINED UGLINESS; ANXIETY DISORDERS; COMORBIDITY; SAMPLE; TRIAL; EPIDEMIOLOGY AB Background. Body dysmorphic disorder (BDD) is a highly distressing and impairing disorder characterized by a preoccupation with imagined or slight physical defects in appearance. Well designed studies on its prevalence and on base rates for diagnostic criteria are rare. Therefore this study aimed to reveal prevalence rates of BDD in the general population and to examine clinical features associated with BDD. Method. Of 4152 selected participants 2552, aged 14-99 years, participated in this German nationwide survey. Participants were carefully selected to ensure that the sample was representative; they were visited by a study assistant who provided instructions and help if needed. Participation rate was 62(.)3%. DSM-IV criteria for BDD, as well as subthreshold features (e.g. individuals who consider some part(s) of their body as ugly or disfigured, but do not fulfill all BDD criteria) were examined. We also assessed suicidal ideation associated with the belief of having an ugly body part, as well as the desire for cosmetic surgery. Furthermore, somatization symptoms were assessed. Results. The prevalence of current BDD was 1(.)7% (CI 1(.)2-2(.)1%). Individuals with BDD reported higher rates of suicidal ideation (19% v. 3%) and suicide attempts due to appearance concerns (7% v. 1%) than individuals who did not meet criteria for BDD. Somatization scores were also increased in individuals with BDD, relative to those without. BDD was associated with lower financial income, lower rates of living with a partner, and higher rates of unemployment. Conclusions. Our study shows that self-reported BDD is relatively common and associated with significant morbidity. C1 Univ Marburg, Dept Clin Psychol, D-35032 Marburg, Germany. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Leipzig, D-7010 Leipzig, Germany. RP Rief, W (reprint author), Univ Marburg, Dept Clin Psychol, Gutenbergstr 18, D-35032 Marburg, Germany. EM rief@staff.uni-marburg.de NR 32 TC 161 Z9 167 U1 3 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUN PY 2006 VL 36 IS 6 BP 877 EP 885 DI 10.1017/S0033291706007264 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 052NC UT WOS:000238239400015 PM 16515733 ER PT J AU Ablon, JS Levy, RA Katzenstein, T AF Ablon, JS Levy, RA Katzenstein, T TI Beyond brand names of psychotherapy: Identifying empirically supported change processes SO PSYCHOTHERAPY LA English DT Article DE panic disorder; psychotherapy process and outcome; psychodynamic psychotherapy; change processes ID COLLABORATIVE RESEARCH-PROGRAM; CONTROLLED CLINICAL-TRIALS; MENTAL-HEALTH TREATMENT; PANIC DISORDER; THERAPEUTIC ALLIANCE; BEHAVIORAL TREATMENT; NATIONAL INSTITUTE; PHARMACOTHERAPY; VALIDITY; QUALITY AB There is considerable debate about which empirical research methods best advance clinical outcomes in psychotherapy. The prevailing tendency has been to test treatment packages using randomized, controlled clinical trials. Recently, focus has shifted to considering how studying the process of change in naturalistic treatments can be a useful complement to controlled trials. Clinicians self-identifying as psychodynamic treated 17 panic disorder patients in naturalistic psychotherapy for an average of 21 sessions. Patients achieved statistically significant reductions in symptoms across all domains. Rates of remission and clinically significant change as well as effect sizes were commensurate with those of empirically supported therapies for panic disorder. Treatment gains were maintained at 6-month follow-up. Intensive analysis of the process of the treatments revealed that integrative elements characterized the treatments: Adherence to cognitive-behavioral process was most characteristic, adherence to interpersonal and psychodynamic process, however, was most predictive of positive outcome. Specific process predictors of outcome were identified using the Psychotherapy Process Q-Set. These findings demonstrate how process research can be used to empirically validate change processes in naturalistic treatments as opposed to treatment packages in controlled trials. C1 Massachusetts Gen Hosp, Dept Psychiat, Psychotherapy Res Program, Newton, MA 02458 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Ablon, JS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychotherapy Res Program, 313 Washington St,Suite 402, Newton, MA 02458 USA. EM sablon@cpsinstitute.org OI Katzenstein, Terese L/0000-0002-2233-500X NR 51 TC 39 Z9 41 U1 3 U2 10 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD SUM PY 2006 VL 43 IS 2 BP 216 EP 231 DI 10.1037/0033-3204.43.2.216 PG 16 WC Psychology, Clinical SC Psychology GA 057MJ UT WOS:000238599600008 PM 22122039 ER PT J AU Principe, JM Marci, CD Glick, DM Ablon, JS AF Principe, Jean M. Marci, Carl D. Glick, Debra M. Ablon, J. Stuart TI The relationship among patient contemplation, early alliance, and continuation in psychotherapy SO PSYCHOTHERAPY LA English DT Article DE therapeutic alliance; contemplation; readiness to change; psychological distress; continuation; ambivalence ID THERAPEUTIC ALLIANCE; WORKING ALLIANCE; RESEARCH-PROJECT; TERMINATION; SUBTYPES AB The present study examined the relationship among contemplation stage of readiness to change, formation of an early therapeutic alliance, and psychological distress following the first session of psychotherapy. Significant correlations between the contemplation scores and the therapeutic alliance were found for patients in the contemplation stage. Although contemplation scores were not a factor in return for a second session of psychotherapy, the bond subscale of the alliance inventory did significantly contribute to whether patients returned for therapy. Patient psychological distress was not a significant factor in predicting the early alliance. Results indicate a need for further focus on contemplation with its inherent ambivalence, its relationship to alliance, and continuation in early psychotherapy. C1 Massachusetts Gen Hosp, Psychotherapy Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Bowdoin Coll, Counseling Serv, Brunswick, ME 04011 USA. RP Marci, CD (reprint author), Massachusetts Gen Hosp, Psychotherapy Res Program, 15 Parkman St WACC 812, Boston, MA 02114 USA. EM cmarci@partners.org NR 38 TC 12 Z9 12 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD SUM PY 2006 VL 43 IS 2 BP 238 EP 243 DI 10.1037/0033-3204.43.2.238 PG 6 WC Psychology, Clinical SC Psychology GA 057MJ UT WOS:000238599600010 PM 22122041 ER PT J AU Singh, H Petersen, LA Thomas, EJ AF Singh, H Petersen, LA Thomas, EJ TI Understanding diagnostic errors in medicine: a lesson from aviation SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID SHARED MENTAL MODELS; SITUATION AWARENESS; COGNITIVE ERRORS; DYNAMIC-SYSTEMS; ADVERSE EVENTS; PERFORMANCE; CARE; CONSEQUENCES; STRATEGIES; COLORADO AB The impact of diagnostic errors on patient safety in medicine is increasingly being recognized. Despite the current progress in patient safety research, the understanding of such errors and how to prevent them is inadequate. Preliminary research suggests that diagnostic errors have both cognitive and systems origins. Situational awareness is a model that is primarily used in aviation human factors research that can encompass both the cognitive and the systems roots of such errors. This conceptual model offers a unique perspective in the study of diagnostic errors. The applicability of this model is illustrated by the analysis of a patient whose diagnosis of spinal cord compression was substantially delayed. We suggest how the application of this framework could lead to potential areas of intervention and outline some areas of future research. It is possible that the use of such a model in medicine could help reduce errors in diagnosis and lead to significant improvements in patient care. Further research is needed, including the measurement of situational awareness and correlation with health outcomes. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Div Hlth Policy & Qual, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Texas, Ctr Excellence Patient Safety Res & Practice, Houston, TX USA. Univ Texas, Sch Med, Dept Med, Div Gen Med, Houston, TX 77030 USA. RP Singh, H (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Div Hlth Policy & Qual, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.tmc.edu FU AHRQ HHS [1PO1HS1154401]; NCRR NIH HHS [K12 K12RR17665, K12 RR017665] NR 43 TC 65 Z9 66 U1 2 U2 14 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD JUN PY 2006 VL 15 IS 3 BP 159 EP 164 DI 10.1136/qshc.2005.016444 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 049PL UT WOS:000238028400007 PM 16751463 ER PT J AU Stelfox, HT Palmisani, S Scurlock, C Orav, EJ Bates, DW AF Stelfox, HT Palmisani, S Scurlock, C Orav, EJ Bates, DW TI The "To Err is Human" report and the patient safety literature SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID MEDICAL ERRORS; QUALITY; SERIES; EVENTS; HEALTH; HARM AB Background: The "To Err is Human'' report published by the Institute of Medicine (IOM) in 1999 called for a national effort to make health care safer. Although the report has been widely credited with spawning efforts to study and improve safety in health care, there has been limited objective assessment of its impact. We evaluated the effects of the IOM report on patient safety publications and research awards. Methods: We searched MEDLINE to identify English language articles on patient safety and medical errors published between 1 November 1994 and 1 November 2004. Using interrupted time series analyses, changes in the number, type, and subject matter of patient safety publications were measured. We also examined federal ( US only) funding of patient safety research awards for the fiscal years 1995 - 2004. Results: A total of 5514 articles on patient safety and medical errors were published during the 10 year study period. The rate of patient safety publications increased from 59 to 164 articles per 100 000 MEDLINE publications ( p< 0.001) following the release of the IOM report. Increased rates of publication were observed for all types of patient safety articles. Publications of original research increased from an average of 24 to 41 articles per 100 000 MEDLINE publications after the release of the report ( p, 0.001), while patient safety research awards increased from 5 to 141 awards per 100 000 federally funded biomedical research awards ( p, 0.001). The most frequent subject of patient safety publications before the IOM report was malpractice (6% v 2%, p< 0.001) while organizational culture was the most frequent subject (1% v 5%, p< 0.001) after publication of the report. Conclusions: Publication of the report "To Err is Human'' was associated with an increased number of patient safety publications and research awards. The report appears to have stimulated research and discussion about patient safety issues, but whether this will translate into safer patient care remains unknown. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Roma La Sapienza, Fac Med 2, St Andrea Hosp, Dept Anesthesia & Intens Care Med, Rome, Italy. Mt Sinai Hosp & Sch Med, Dept Anesthesia, New York, NY 10029 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Partners Healthcare Syst, Boston, MA USA. RP Stelfox, HT (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 309, Boston, MA 02114 USA. EM hstelfox@partners.org NR 23 TC 125 Z9 129 U1 4 U2 16 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD JUN PY 2006 VL 15 IS 3 BP 174 EP 178 DI 10.1136/qshc.2006.017947 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 049PL UT WOS:000238028400010 PM 16751466 ER PT J AU Thrall, JH AF Thrall, JH TI Education and cultural development of the health care work force - Part I. The health professions SO RADIOLOGY LA English DT Editorial Material ID QUALITY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Founders House 216,55 Fruit St, Boston, MA 02114 USA. EM jthrall@partners.org NR 9 TC 3 Z9 3 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 2006 VL 239 IS 3 BP 621 EP 625 DI 10.1148/radiol.2393060291 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 045JO UT WOS:000237738600002 PM 16714452 ER PT J AU Shi, R Schraedley-Desmond, P Napel, S Olcott, EW Jeffrey, RB Yee, J Zalis, ME Margolis, D Paik, DS Sherbondy, AJ Sundaram, P Beaulieu, CF AF Shi, R Schraedley-Desmond, P Napel, S Olcott, EW Jeffrey, RB Yee, J Zalis, ME Margolis, D Paik, DS Sherbondy, AJ Sundaram, P Beaulieu, CF TI CT colonography: Influence of 3D viewing and polyp candidate features on interpretation with computer-aided detection SO RADIOLOGY LA English DT Article ID COLONIC POLYPS; TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; COLORECTAL NEOPLASIA; DIAGNOSIS SCHEME; FEASIBILITY; POPULATION; SCREEN AB Purpose: To retrospectively determine if three-dimensional (3D) viewing improves radiologists' accuracy in classifying true-positive (TP) and false-positive (FP) polyp candidates identified with computer-aided detection (CAD) and to determine candidate polyp features that are associated with classification accuracy, with known polyps serving as the reference standard. Materials and Methods: Institutional review board approval and informed consent were obtained; this study was HIPAA compliant. Forty-seven computed tomographic (CT) colonography data sets were obtained in 26 men and 10 women (age range, 42 - 76 years). Four radiologists classified 705 polyp candidates (53 TP candidates, 652 FP candidates) identified with CAD; initially, only two-dimensional images were used, but these were later supplemented with 3D rendering. Another radiologist unblinded to colonoscopy findings characterized the features of each candidate, assessed colon distention and preparation, and defined the true nature of FP candidates. Receiver operating characteristic curves were used to compare readers' performance, and repeated-measures analysis of variance was used to test features that affect interpretation. Results: Use of 3D viewing improved classification accuracy for three readers and increased the area under the receiver operating characteristic curve to 0.96 - 0.97 (P < .001). For TP candidates, maximum polyp width (P = .038), polyp height (P = .019), and preparation (P = .004) significantly affected accuracy. For FP candidates, colonic segment (P = .007), attenuation (P < .001), surface smoothness (P < .001), distention (P = .034), preparation (P < .001), and true nature of candidate lesions (P < .001) significantly affected accuracy. Conclusion: Use of 3D viewing increases reader accuracy in the classification of polyp candidates identified with CAD. Polyp size and examination quality are significantly associated with accuracy. C1 Stanford Univ, Med Ctr, Dept Radiol, James H Clark Ctr, Stanford, CA 94305 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Shi, R (reprint author), Stanford Univ, Med Ctr, Dept Radiol, James H Clark Ctr, 318 Campus Dr,Room S324, Stanford, CA 94305 USA. EM rshi@stanford.edu FU NCI NIH HHS [R01 CA72023]; NIGMS NIH HHS [U54 GM072970, 1 U54 GM072970] NR 30 TC 19 Z9 21 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2006 VL 239 IS 3 BP 768 EP 776 DI 10.1148/radiol.2393050418 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 045JO UT WOS:000237738600018 PM 16714460 ER PT J AU Stone, ME AF Stone, Martha E. TI The Greenwood encyclopedia of African American literature. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, References Serv, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, References Serv, 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 2006 VL 45 IS 4 BP 343 EP 344 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 086WR UT WOS:000240704200022 ER PT J AU Hess, DR Fink, JB T Venkataraman, S Kim, IK Myers, TR D Tano, B AF Hess, DR Fink, JB T Venkataraman, S Kim, IK Myers, TR D Tano, B TI The history and physics of heliox SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT Symposium on Heliox Therapy CY DEC 03, 2005 CL San Antonio, TX SP Amer Assoc Respiratory Care DE density; heliox; helium; thermal conductivity; viscosity ID OXYGEN MIXTURES; GAS AB Since the discovery of helium in 1868, it has found numerous applications in industry and medicine. Its low density makes helium potentially valuable in respiratory care applications, to reduce work of breathing, improve distribution of ventilation, reduce minute volume requirement, and improve aerosol delivery. This review includes a brief history of the use of heliox (a mixture of helium and oxygen) and addresses issues related to the physics of gas flow when heliox is used. Specifically covered are the Hagen-Poiseuille equation, laminar versus turbulent flow, the Reynolds number, orifice flow, Bernoulli's principle, Graham's law, wave speed, and thermal conductivity. C1 Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Nektar Therapeut, Mountain View, CA USA. Childrens Hosp Pittsburgh, Pediat Intens Care Unit, Pittsburgh, PA 15213 USA. Kosair Childrens Hosp, Div Pediat Emergency Med, Louisville, KY USA. Rainbow Babies & Childrens Hosp, Asthma Ctr, Cleveland, OH 44106 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 19 TC 40 Z9 41 U1 2 U2 3 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD JUN PY 2006 VL 51 IS 6 BP 608 EP 612 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 050SK UT WOS:000238108300002 PM 16723037 ER PT J AU Hess, DR AF Hess, DR TI Heliox and noninvasive positive-pres sure ventilation: A role for heliox in exacerbations of chronic obstructive pulmonary disease? SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT Symposium on Heliox Therapy CY DEC 03, 2005 CL San Antonio, TX SP Amer Assoc Respiratory Care DE chronic obstructive pulmonary disease; heliox; mechanical ventilation; noninvasive positive-pressure ventilation ID MAXIMAL EXPIRATORY FLOW; MECHANICAL VENTILATION; DYNAMIC HYPERINFLATION; RESPIRATORY-FAILURE; DENSITY DEPENDENCE; OXYGEN MIXTURES; COPD PATIENTS; EXERCISE; SUPPORT; WORK AB Evidence-based respiratory therapy for exacerbations of chronic obstructive pulmonary disease (COPD) includes oxygen, inhaled bronchodilators, and noninvasive positive-pressure ventilation. Examining the physics of gas flow, a case can be made either for or against the use of helium-oxygen mixture (heliox) in the care of patients with COPD. The evidence for the use of heliox in patients with COPD exacerbation is not strong at present. Most of the peer-reviewed literature consists of case reports, case series, and physiologic studies in small samples of carefully selected patients. Some patients with COPD exacerbation have a favorable physiologic response to heliox therapy, but predicting who will be a responder is difficult. Moreover, the use of heliox is hampered by the lack of widespread availability of an approved heliox delivery system. Appropriately designed randomized controlled trials with patient-important outcomes, such as avoidance of intubation, decreased intensive-care-unit and hospital days, and decreased cost of therapy, are sorely needed to establish the role of heliox in patients with COPD exacerbation, including those receiving noninvasive positive-pressure ventilation. Lacking such evidence, the use of heliox in patients with COPD exacerbation cannot be considered standard therapy. C1 Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 47 TC 12 Z9 13 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 RESPIR CARE JI Respir. Care PD JUN PY 2006 VL 51 IS 6 BP 640 EP 650 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 050SK UT WOS:000238108300006 PM 16723041 ER PT J AU Dransfield, MT Davis, JJ Gerald, LB Bailey, WC AF Dransfield, MT Davis, JJ Gerald, LB Bailey, WC TI Racial and gender differences in susceptibility to tobacco smoke among patients with chronic obstructive pulmonary disease SO RESPIRATORY MEDICINE LA English DT Article DE chronic obstructive; pulmonary disease; smoking; race ID CIGARETTE-SMOKING; AFRICAN-AMERICANS; LUNG-FUNCTION; COPD; MORTALITY; VALUES; ADULTS; HEALTH; ASTHMA AB Background: Although chronic obstructive pulmonary disease (COPD) has been considered a disease of Caucasian men, recent data show mortality rising faster among women and African-Americans. Some have suggested these groups are more susceptible to tobacco smoke. We examined this issue in our own population of COPD patients. Methods: Beginning in March 2003 we prospectively developed a COPD research database to facilitate recruitment for clinical trials. Enrollees are recruited from clinics and paid advertising and their demographics, medical/smoking histories, and spirometric data are recorded. We examined the smoking histories and pulmonary function of enrollees over 45, with >= 20 pack-years of smoking, FEV1/FVC (forced expiratory volume forced vital capacity) < 0.70, and a race-adjusted post-bronchoditator FEV1 < 80%. The primary outcome was the toss of lung function per pack-year smoked, or Susceptibility Index (SI), calculated using the formula: (% predicted FEV1-100)/pack-years. Results: A total of 585 patients enrolled during the study period and 330 met our inclusion criteria. Caucasians were older than African-Americans (63 vs. 58, P = 0.0003) and had more pack-years of smoking (57 vs. 43, P = 0.0003). There were no differences in lung function or bronchodilator reversibility among the racial or gender subgroups. Caucasians had less loss of lung function per pack-year smoked than African-Americans (SI = -1.02% vs. -1.34%, P = 0.007) and men less than women (SI = -0.98% vs. -1.21%, P = 0.001). Caucasian mates appeared relatively protected from tobacco smoke (SI = -0.93%), while African-American women appeared most susceptible (SI = -1.42%). Conclusions: There are important differences in racial and gender susceptibility to tobacco smoke among patients with COPD. African-American females appear to be at highest risk and may benefit most from smoking cessation. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Alabama, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Pulm Sect, Birmingham, AL 35233 USA. RP Dransfield, MT (reprint author), 215 THT,1900 Univ Blvd, Birmingham, AL 35294 USA. EM mdransfield99@msn.com NR 26 TC 61 Z9 63 U1 0 U2 5 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD JUN PY 2006 VL 100 IS 6 BP 1110 EP 1116 DI 10.1016/j.rmed.2005.09.019 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 049KZ UT WOS:000238016500022 PM 16236491 ER PT J AU Jassal, DS Weyman, AE AF Jassal, Davinder S. Weyman, Arthur E. TI Infective endocarditis in the era of intracardiac devices: An echocardiographic perspective SO REVIEWS IN CARDIOVASCULAR MEDICINE LA English DT Review DE infective endocarditis; transthoracic echocardiography; transesophageal echocardiography; valvular vegetation; native mitral valve; prosthetic valve endocarditis ID MULTIPLANE TRANSESOPHAGEAL ECHOCARDIOGRAPHY; AMERICAN-HEART-ASSOCIATION; PACEMAKER LEAD INFECTION; RIGHT-SIDED ENDOCARDITIS; DIAGNOSTIC-VALUE; TRANSTHORACIC ECHOCARDIOGRAPHY; VALVULAR VEGETATIONS; PERMANENT PACEMAKERS; SURGICAL-MANAGEMENT; VALVE ENDOCARDITIS AB Although the role of echocardiography is well established in the management of native valve and prosthetic valve endocarditis, the recent introduction of intracardiac devices, including pacemakers, implantable defibrillators, closure devices, and ventricular assist devices, has expanded its utility. Echocardiography permits the direct imaging of valvular vegetations, and it allows for the identification of structural complications of endocarditis. It is useful for characterizing the hemodynamic consequences of the infection. It can also provide prognostic information concerning risk of embolization and/or need for cardiac surgery. This article reviews the roles of transthoracic echocardiography and transesophageal echocardiography in the evaluation of patients with native valve endocarditis, prosthetic valve endocarditis, and infections involving a variety of nonvalvular cardiovascular devices. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div,Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Jassal, DS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div,Cardiac Ultrasound Lab, Boston, MA 02114 USA. NR 56 TC 4 Z9 6 U1 0 U2 2 PU MEDREVIEWS PI NEW YORK PA 1333 BROADWAY, STE 400, NEW YORK, NY 10018 USA SN 1530-6550 J9 REV CARDIOVASC MED JI Rev. Cardiovasc. Med. PD SUM PY 2006 VL 7 IS 3 BP 119 EP 129 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 096HD UT WOS:000241367300002 PM 17088857 ER PT J AU Misra, M Klibanski, A AF Misra, Madhusmita Klibanski, Anne TI Anorexia nervosa and osteoporosis SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE anorexia nervosa; bone density; bone turnover; hypogonadism; hypercortisolemia; GH resistance ID BONE-MINERAL DENSITY; GROWTH-HORMONE-SECRETION; ADOLESCENT GIRLS; FEMALE ADOLESCENTS; BULIMIA-NERVOSA; PLASMA-LEVELS; YOUNG-WOMEN; PEPTIDE YY; HEALTHY ADOLESCENTS; CYTOKINE PRODUCTION AB Anorexia nervosa (AN), a condition of severe undernutrition, is associated with low bone mineral density (BMD) in adults and adolescents. Whereas adult women with AN have an uncoupling of bone turnover markers with increased bone resorption and decreased bone formation markers, adolescents with AN have decreased bone turnover overall. Possible contributors to low BMD in AN include hypoestrogenism and hypoandrogenism, undernutrition with decreased lean body mass, and hypercortisolemia. IGF-I, a known bone trophic factor, is reduced despite elevated growth hormone (GH) levels, leading to an acquired GH resistant state. Elevated ghrelin and peptide YY levels may also contribute to impaired bone metabolism. Weight recovery is associated with recovery of BMD but this is often partial, and long-term and sustained weight recovery may be necessary before significant improvements are observed. Anti-resorptive therapies have been studied in AN with conflicting results. Oral estrogen does not increase BMD or prevent bone loss in AN. The combination of bone anabolic and anti-resorptive therapy (rhIGF-I with oral estrogen), however, did result in a significant increase in BMD in a study of adult women with AN. A better understanding of the pathophysiology of low BMD in AN, and development of effective therapeutic strategies is critical. This is particularly so for adolescents, who are in the process of accruing peak bone mass, and in whom a failure to attain peak bone mass may occur in AN in addition to loss of established bone. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. RP Misra, M (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM mmisra@partners.org FU NCRR NIH HHS [K23 RR018851, M01-RR-01066]; NIDDK NIH HHS [R01DK062249, R01DK52625] NR 96 TC 62 Z9 64 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD JUN PY 2006 VL 7 IS 1-2 BP 91 EP 99 DI 10.1007/s11154-006-9005-1 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 142CE UT WOS:000244625800009 PM 16972186 ER PT J AU de Prado, AP Fernandez-Vazquez, F Cuellas-Ramon, JC Gibson, CM AF Perez de Prado, Armando Fernandez-Vazquez, Felipe Cuellas-Ramon, J. Carlos Gibson, C. Michael TI Coronary angiography: Beyond coronary anatomy SO REVISTA ESPANOLA DE CARDIOLOGIA LA Spanish DT Review DE coronary angiography; coronary blood flow; myocardial perfusion ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT-ELEVATION; TIMI FRAME COUNT; LEFT-VENTRICULAR FUNCTION; TISSUE-PLASMINOGEN-ACTIVATOR; GLYCOPROTEIN IIB/IIIA INHIBITION; INTRAVENOUS THROMBOLYTIC THERAPY; NO-REFLOW PHENOMENON; PRIMARY ANGIOPLASTY; BLOOD-FLOW AB Although technical advances enable normal epicardial coronary artery blood flow to be restored in most patients suffering myocardial infarction, restoration of blood flow is not always followed by improved myocardial perfusion. Recently, therefore, interest in the assessment of myocardial perfusion has grown, and a number of different assessment methods are available. The aim of this article was to provide an evaluation of the additional information that can be obtained from the widely used technique of conventional coronary angiography. We present a review of the data on epicardial coronary artery blood flow (both semiquantitative and quantitative) and on microvascular blood flow that can be obtained using coronary angiography and discuss their prognostic significance. C1 Hosp Leon, Secc Cardiol Intervencionista, Serv Cardiol, Leon 24008, Spain. Harvard Univ, Sch Med, TIMI Study Grp, Boston, MA USA. RP de Prado, AP (reprint author), Hosp Leon, Secc Cardiol Intervencionista, Serv Cardiol, Altos Nava S-N, Leon 24008, Spain. EM aperez@secardiologia.es OI Perez de Prado, Armando/0000-0003-3283-0597 NR 142 TC 5 Z9 5 U1 0 U2 0 PU EDICIONES DOYMA S/L PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD JUN PY 2006 VL 59 IS 6 BP 596 EP 608 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 064NQ UT WOS:000239096800011 ER EF